Click for Credit: Endometriosis surgery benefits; diabetes & aging; more

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Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

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Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

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Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

To take the posttest, go to: https://bit.ly/2ExDV7o
Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

Here are 5 articles from the March issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Endometriosis surgery: Women can expect years-long benefits

To take the posttest, go to: https://bit.ly/2Ez8mdu
Expires January 3, 2019

2. Cerebral small vessel disease progression linked to MCI in hypertensive patients

To take the posttest, go to: https://bit.ly/2ExDV7o
Expires January 4, 2019

3. Adult atopic dermatitis is fraught with dermatologic comorbidities

To take the posttest, go to: https://bit.ly/2Vl7E9a
Expires January 11, 2019

4. Antidepressants tied to greater hip fracture incidence in older adults

To take the posttest, go to: https://bit.ly/2GRfMeH
Expires January 4, 2019

5. Researchers exploring ways to mitigate aging’s impact on diabetes

To take the posttest, go to: https://bit.ly/2tFxF7v
Expires January 8, 2019

Issue
Clinician Reviews - 29(3)
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Clinician Reviews - 29(3)
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Many common dermatologic drugs can be safely used during pregnancy

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– With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.

Dr. Jenny Murase

But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”

As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.

The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.

 

 

Corticosteroids

These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.

In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.

 

 

Antihistamines

First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).

Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.

“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.

 

 

Immunosuppressants

Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.

“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”

Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.

Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”

She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”

Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.

Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.

 

 

Biologics

Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.

There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.

“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”

Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”

 

 

Pemphigus

Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said

Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”

Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.

“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.

She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.

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– With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.

Dr. Jenny Murase

But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”

As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.

The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.

 

 

Corticosteroids

These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.

In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.

 

 

Antihistamines

First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).

Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.

“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.

 

 

Immunosuppressants

Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.

“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”

Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.

Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”

She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”

Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.

Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.

 

 

Biologics

Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.

There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.

“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”

Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”

 

 

Pemphigus

Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said

Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”

Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.

“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.

She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.

 

– With proper counseling and oversight, many drugs used for psoriasis, pemphigus, and atopic dermatitis are safe to use during pregnancy, Jenny Murase, MD, said at the annual meeting of the American Academy of Dermatology.

Dr. Jenny Murase

But it’s important to have an early talk about potential pregnancies, because most dermatologists don’t think about it unless a patient is taking a known teratogen, like isotretinoin, said Dr. Murase of the University of California, San Francisco. “It’s only about 10% of the time that the dermatologist brings it up. In patients with these chronic skin diseases, we need to address family planning proactively. Most women don’t discover they’re pregnant until they’re 2-5 weeks along, and by that time the development of major organs has already started.”

As part of her expertise in this topic, Dr. Murase published two comprehensive reports on the safety of dermatologic drugs in pregnancy and lactation. They were grouped according to the newest federal guidance, the Food and Drug Administration Pregnancy and Lactation Label Ruling. Issued in 2014, it requires the inclusion of any contact information for drug registries and covers reproductive risks or both males and females. Slowly being phased in as new drugs are approved, the ruling is replacing the old category A, B, and C.

The articles were published in the Journal of the American Academy of Dermatology and in the international Journal of Women’s Dermatology, an open-access journal Dr. Murase founded.

 

 

Corticosteroids

These dermatology workhorses are largely safe in pregnancy, Dr. Murase said. Some very early reports suggested that systemic cortisone might be associated with oral clefts, but that has never been borne out in prospective data. Prednisone may be the safest as it has the most limited placental transport; betamethasone and dexamethasone cross the placenta easily.

In a Cochrane review, only one study showed an increased risk of orofacial clefts. A 2013 study of about 10,000 women suggested an increased risk of low birth weight associated with a total dose of more than 300 grams during the pregnancy.

 

 

Antihistamines

First-generation antihistamines, including hydroxyzine, have been used as antiemetics in pregnant women. Hydroxyzine is generally considered safe, but should be discussed carefully, as it carries a slightly increased risk of congenital malformations (5.8% vs. 2.3% background risk).

Newborns exposed to large doses of hydroxyzine (150 mg or more daily) have also exhibited withdrawal symptoms at birth, including irritability, poor feeding, and tonic-clinic seizures.

“Antihistamines can exert oxytocin-like effects, especially in overdose or when given intravenously, so please avoid using them in the last month of pregnancy. There have also been a few reports of retrolental fibroplasia in preterm infants who were exposed to antihistamines within 2 weeks of delivery,” Dr. Murase said.

 

 

Immunosuppressants

Mycophenolate is not compatible with pregnancy. In 2007, the FDA changed the labeling of mycophenolate from category C to D, because of reports of congenital malformations arising from the U.S. National Transplantation Pregnancy Registry and other sources.

“You need to treat these patients like you do someone who is going on isotretinoin,” Dr. Murase said. “Any woman prescribed it should be on mandatory contraception at least 4 weeks before beginning the medication and for 6 weeks after completing treatment.”

Thus far there are no reported pregnancy-related safety issues with dupilumab, although data are scarce.

Pregnancy itself exerts a positive effect on psoriasis in many women, but not all. “About half the time a women will improve,” Dr. Murase said. “A quarter of the time, there’s no change and a quarter of the time, she’ll get worse. But the ones who do improve, often improve dramatically with about 80% body surface area clearance.”

She considers light therapy to be the safest treatment during pregnancy, with one caveat: Ultraviolet light can degrade some vitamins, including folic acid. “Every one of my patients of childbearing age I have on folic acid or a prenatal vitamin just in case. You have to be proactive here.”

Cyclosporine appears to be “quite safe,” she said. The possibility of intrauterine growth restriction seen in some studies is tough to tease out, because it was reported mainly in transplant populations among women with other medical comorbidities. Children from these pregnancies have been followed through toddlerhood and showed no neurodevelopmental or kidney issues.

Apremilast is a category C drug. Some animal data suggested increased spontaneous abortions and fetal demise with doses given at two to four times the human dose.

 

 

Biologics

Antibodies are an interesting lot, Dr. Murase noted. Maternal antibodies are transported to the fetus across the villi by Fc receptor; most of this transfer happens during the third trimester. The large, hydrophilic monoclonal antibodies infliximab, adalimumab, and ustekinumab travel this way as well. Cord blood can contain 50% higher serum levels than in maternal blood. Etanercept, however, is a fusion protein that diffuses across the placenta. Cord blood levels generally exceed maternal levels by less than 7%.

There is one published report of a fetal death associated with maternal infliximab for Crohn’s disease. The infant was healthy until it received a Bacillus Calmette–Guerin vaccine. It then developed widespread eczematous dermatitis, head lag, and poor weight gain and died at 4.5 months.

“This is another important counseling point,” Dr. Murase said. “Babies who have been exposed to infliximab in utero can’t have that vaccination in the first 9 months of life.”

Perhaps the safest bet for a pregnant women who needs a biologic is PEGylated certolizumab. “Certolizumab is the only PEGylated anti-TNF [tumor necrosis factor] without an Fc region; study of patients greater than 30 weeks pregnant certolizumab levels were below 0.032 mcg/mL in 13 of 14 infant samples at birth.”

 

 

Pemphigus

Pemphigus (impetigo herpetiformous) is a serious dermatologic disorder that can manifest in the third trimester, and affect the fetus as well as the mother. “You have to take even mild cases very seriously, because there’s no distinct correlation between the extent of neonatal involvement and the extent of maternal disease,” Dr. Murase said

Oral pemphigus in the mother is especially worrisome, she added. “Fetal skin shares the same desmoglein-3 profile as adult oral mucosa, and neonatal pemphigus is more likely if mother has oral disease. There’s an increased risk of fetal demise as well.”

Treatment would generally start with topical steroids, progressing to systemic low-dose corticosteroids. If more than 20 mg of prednisone a day is required, consider intravenous immunoglobulin (IVIG), azathioprine, dapsone, or rituximab.

“IVIG is very safe for pregnant women, and in fact reproductive endocrinologists use this to increase the chance of pregnancy for infertility cases,” Dr. Murase said.

She reported relationships with Regeneron, UCB, Dermira, and Genzyme/Sanofi.

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ACOG: Avoid inductions before 39 weeks unless medically necessary

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Sat, 03/02/2019 - 10:56

 

Babies should not be delivered before 39 0/7 weeks’ gestation by means besides spontaneous vaginal delivery, in the absence of medical indications for an earlier delivery.

Herjua/Thinkstock

“Although there are specific indications for delivery before 39 weeks of gestation, a nonmedically indicated early-term delivery should be avoided,” wrote the authors of the new opinion, developed by the American College of Obstetricians and Gynecologists committee on obstetric practice and the Society for Maternal-Fetal Medicine.

The opinion, which replaces a 2013 statement, clarifies that their recommendations include avoiding cesarean delivery, labor induction, and cervical ripening before 39 0/7 weeks of gestation, unless a medical indication exists for earlier delivery.

The new opinion statement relied, in part, on a recent systematic review finding that late-preterm and early-term children do not fare as well as do term-delivered children in a variety of cognitive and educational domains. The opinion statement acknowledges that it’s not clear why children delivered earlier are showing performance difficulties and that it is possible that medical indications for an earlier delivery contributed to the differences.

Immediate outcomes for neonates delivered in the late preterm and early term period also are worse, compared with those delivered at term, according to several studies cited in the opinion. For example, composite morbidity was higher for infants delivered at both 37 and 38 weeks gestation, compared with those delivered at 39 weeks, with adjusted odds ratios for the composite outcome of 2.1 and 1.5, respectively (N Engl J Med. 2009 Jan 8;360[2]:111-20).

And lung maturity alone should not guide delivery, wrote the authors of the opinion. “Because nonrespiratory morbidities also are increased in early-term deliveries, documentation of fetal pulmonary maturity does not justify an early nonmedically indicated delivery,” they said, adding that physicians should not perform amniocentesis to determine lung maturity in an effort to guide delivery timing.

Because intrapartum demise remains a risk as long as a woman is pregnant, the potential for adverse neonatal outcomes with early delivery has to be balanced against the risk of stillbirth with continued gestation, the opinion authors acknowledged. But, they said, this question has been addressed by “multiple studies using national population level data,” which show that “even as the gestational age at term has increased in response to efforts to reduce early elective delivery, these efforts have not adversely affected stillbirth rates nationally or even in states with the greatest reductions in early elective delivery.”

Formal programs to reduce nonmedically indicated early-term deliveries have been successful. For example, the state of South Carolina achieved a reduction of almost 50% in nonmedically indicated early-term deliveries over the course of just 1 year. The South Carolina Birth Outcomes Initiative led a collaborative effort to institute a “hard-stop” policy against nonmedically indicated early-term deliveries that resulted in an absolute 4.7% decrease in late-preterm birth during 2011-2012. Similar efforts in Oregon and Ohio have reported significant reductions as well, with no increases in adverse neonatal outcomes.

Various policy approaches have been tried to achieve a reduction in nonmedically indicated late-preterm and early-term birth. These range from awareness raising and education, to “soft-stop” policies in which health care providers agree not to deliver before 39 weeks without medical indication, to “hard-stop” policies in which hospitals prohibit the nonindicated deliveries. In one comparative outcomes study, the hard-stop policy was the most effective, with a drop from 8.2% to 1.7% in nonindicated early deliveries, but the soft-stop policy also produced a decrease from 8.4% to 3.3% (P = .007 and .025, respectively). The educational approach didn’t produce a significant drop in nonmedically indicated early deliveries (Am J Obstet Gynecol. 2010 Nov;203[5]:449.e1-6).

In a separate, preexisting statement (Obstet Gynecol. 2019;133:e151-5), ACOG has outlined the management of medically indicated late-preterm and early-term deliveries and has developed an app (www.acog.org/acogapp) as a decision tool for indicated deliveries.

Examples cited by the current opinion statement authors of medical indications for early delivery include maternal factors such as preeclampsia, gestational hypertension, and poorly controlled diabetes. Placentation problems, fetal growth restriction, and prior cesarean deliveries also may warrant earlier delivery, as may a host of other complications. If an earlier delivery is planned, the committee authors recommend full discussion with the patient and clear documentation of the indications and discussion.

SOURCE: Obstet Gynecol. 2019 Feb;133[2]:e156-63.

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Babies should not be delivered before 39 0/7 weeks’ gestation by means besides spontaneous vaginal delivery, in the absence of medical indications for an earlier delivery.

Herjua/Thinkstock

“Although there are specific indications for delivery before 39 weeks of gestation, a nonmedically indicated early-term delivery should be avoided,” wrote the authors of the new opinion, developed by the American College of Obstetricians and Gynecologists committee on obstetric practice and the Society for Maternal-Fetal Medicine.

The opinion, which replaces a 2013 statement, clarifies that their recommendations include avoiding cesarean delivery, labor induction, and cervical ripening before 39 0/7 weeks of gestation, unless a medical indication exists for earlier delivery.

The new opinion statement relied, in part, on a recent systematic review finding that late-preterm and early-term children do not fare as well as do term-delivered children in a variety of cognitive and educational domains. The opinion statement acknowledges that it’s not clear why children delivered earlier are showing performance difficulties and that it is possible that medical indications for an earlier delivery contributed to the differences.

Immediate outcomes for neonates delivered in the late preterm and early term period also are worse, compared with those delivered at term, according to several studies cited in the opinion. For example, composite morbidity was higher for infants delivered at both 37 and 38 weeks gestation, compared with those delivered at 39 weeks, with adjusted odds ratios for the composite outcome of 2.1 and 1.5, respectively (N Engl J Med. 2009 Jan 8;360[2]:111-20).

And lung maturity alone should not guide delivery, wrote the authors of the opinion. “Because nonrespiratory morbidities also are increased in early-term deliveries, documentation of fetal pulmonary maturity does not justify an early nonmedically indicated delivery,” they said, adding that physicians should not perform amniocentesis to determine lung maturity in an effort to guide delivery timing.

Because intrapartum demise remains a risk as long as a woman is pregnant, the potential for adverse neonatal outcomes with early delivery has to be balanced against the risk of stillbirth with continued gestation, the opinion authors acknowledged. But, they said, this question has been addressed by “multiple studies using national population level data,” which show that “even as the gestational age at term has increased in response to efforts to reduce early elective delivery, these efforts have not adversely affected stillbirth rates nationally or even in states with the greatest reductions in early elective delivery.”

Formal programs to reduce nonmedically indicated early-term deliveries have been successful. For example, the state of South Carolina achieved a reduction of almost 50% in nonmedically indicated early-term deliveries over the course of just 1 year. The South Carolina Birth Outcomes Initiative led a collaborative effort to institute a “hard-stop” policy against nonmedically indicated early-term deliveries that resulted in an absolute 4.7% decrease in late-preterm birth during 2011-2012. Similar efforts in Oregon and Ohio have reported significant reductions as well, with no increases in adverse neonatal outcomes.

Various policy approaches have been tried to achieve a reduction in nonmedically indicated late-preterm and early-term birth. These range from awareness raising and education, to “soft-stop” policies in which health care providers agree not to deliver before 39 weeks without medical indication, to “hard-stop” policies in which hospitals prohibit the nonindicated deliveries. In one comparative outcomes study, the hard-stop policy was the most effective, with a drop from 8.2% to 1.7% in nonindicated early deliveries, but the soft-stop policy also produced a decrease from 8.4% to 3.3% (P = .007 and .025, respectively). The educational approach didn’t produce a significant drop in nonmedically indicated early deliveries (Am J Obstet Gynecol. 2010 Nov;203[5]:449.e1-6).

In a separate, preexisting statement (Obstet Gynecol. 2019;133:e151-5), ACOG has outlined the management of medically indicated late-preterm and early-term deliveries and has developed an app (www.acog.org/acogapp) as a decision tool for indicated deliveries.

Examples cited by the current opinion statement authors of medical indications for early delivery include maternal factors such as preeclampsia, gestational hypertension, and poorly controlled diabetes. Placentation problems, fetal growth restriction, and prior cesarean deliveries also may warrant earlier delivery, as may a host of other complications. If an earlier delivery is planned, the committee authors recommend full discussion with the patient and clear documentation of the indications and discussion.

SOURCE: Obstet Gynecol. 2019 Feb;133[2]:e156-63.

 

Babies should not be delivered before 39 0/7 weeks’ gestation by means besides spontaneous vaginal delivery, in the absence of medical indications for an earlier delivery.

Herjua/Thinkstock

“Although there are specific indications for delivery before 39 weeks of gestation, a nonmedically indicated early-term delivery should be avoided,” wrote the authors of the new opinion, developed by the American College of Obstetricians and Gynecologists committee on obstetric practice and the Society for Maternal-Fetal Medicine.

The opinion, which replaces a 2013 statement, clarifies that their recommendations include avoiding cesarean delivery, labor induction, and cervical ripening before 39 0/7 weeks of gestation, unless a medical indication exists for earlier delivery.

The new opinion statement relied, in part, on a recent systematic review finding that late-preterm and early-term children do not fare as well as do term-delivered children in a variety of cognitive and educational domains. The opinion statement acknowledges that it’s not clear why children delivered earlier are showing performance difficulties and that it is possible that medical indications for an earlier delivery contributed to the differences.

Immediate outcomes for neonates delivered in the late preterm and early term period also are worse, compared with those delivered at term, according to several studies cited in the opinion. For example, composite morbidity was higher for infants delivered at both 37 and 38 weeks gestation, compared with those delivered at 39 weeks, with adjusted odds ratios for the composite outcome of 2.1 and 1.5, respectively (N Engl J Med. 2009 Jan 8;360[2]:111-20).

And lung maturity alone should not guide delivery, wrote the authors of the opinion. “Because nonrespiratory morbidities also are increased in early-term deliveries, documentation of fetal pulmonary maturity does not justify an early nonmedically indicated delivery,” they said, adding that physicians should not perform amniocentesis to determine lung maturity in an effort to guide delivery timing.

Because intrapartum demise remains a risk as long as a woman is pregnant, the potential for adverse neonatal outcomes with early delivery has to be balanced against the risk of stillbirth with continued gestation, the opinion authors acknowledged. But, they said, this question has been addressed by “multiple studies using national population level data,” which show that “even as the gestational age at term has increased in response to efforts to reduce early elective delivery, these efforts have not adversely affected stillbirth rates nationally or even in states with the greatest reductions in early elective delivery.”

Formal programs to reduce nonmedically indicated early-term deliveries have been successful. For example, the state of South Carolina achieved a reduction of almost 50% in nonmedically indicated early-term deliveries over the course of just 1 year. The South Carolina Birth Outcomes Initiative led a collaborative effort to institute a “hard-stop” policy against nonmedically indicated early-term deliveries that resulted in an absolute 4.7% decrease in late-preterm birth during 2011-2012. Similar efforts in Oregon and Ohio have reported significant reductions as well, with no increases in adverse neonatal outcomes.

Various policy approaches have been tried to achieve a reduction in nonmedically indicated late-preterm and early-term birth. These range from awareness raising and education, to “soft-stop” policies in which health care providers agree not to deliver before 39 weeks without medical indication, to “hard-stop” policies in which hospitals prohibit the nonindicated deliveries. In one comparative outcomes study, the hard-stop policy was the most effective, with a drop from 8.2% to 1.7% in nonindicated early deliveries, but the soft-stop policy also produced a decrease from 8.4% to 3.3% (P = .007 and .025, respectively). The educational approach didn’t produce a significant drop in nonmedically indicated early deliveries (Am J Obstet Gynecol. 2010 Nov;203[5]:449.e1-6).

In a separate, preexisting statement (Obstet Gynecol. 2019;133:e151-5), ACOG has outlined the management of medically indicated late-preterm and early-term deliveries and has developed an app (www.acog.org/acogapp) as a decision tool for indicated deliveries.

Examples cited by the current opinion statement authors of medical indications for early delivery include maternal factors such as preeclampsia, gestational hypertension, and poorly controlled diabetes. Placentation problems, fetal growth restriction, and prior cesarean deliveries also may warrant earlier delivery, as may a host of other complications. If an earlier delivery is planned, the committee authors recommend full discussion with the patient and clear documentation of the indications and discussion.

SOURCE: Obstet Gynecol. 2019 Feb;133[2]:e156-63.

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Malpractice suits are less frequent – but more costly

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Wed, 04/03/2019 - 10:18

Lawsuits against physicians declined across virtually all specialties by more than a quarter over a 10-year span, but the cost to manage legal challenges went up, a recent analysis finds.

From 2007 to 2016, the rate of claims dropped by 27% per 100 doctors from 5.1 to 3.7, according to a review of 124,000 cases by CRICO Strategies, a division of CRICO, the medical liability insurance provider for the Harvard medical community. CRICO’s database of claims contains about 30% of legal cases filed against health providers across the U.S.

For internists, the rate of lawsuits decreased by 35% between 2007 and 2016, according to CRICO data provided to MDedge News. Ob.gyns. saw a 44% drop in claims over the 10-year period, and surgeons experienced a 23% rate decrease. The analysis did not break down the rate of claims by other single subspecialists. Claims decreased by a combined 29% for cardiologists, dermatologists, endocrinologists, family physicians, gastroenterologists, hematologists/oncologists, hospitalists, infectious disease specialists, internists, nephrologists, neurologists, pulmonologists, and rheumatologists/immunologists, according to the report published in February 2019 on CRICO’s website.

The findings are consistent with prior research on claim trends, said Seth Seabury, PhD, a medical liability researcher and director of the Keck-Schaeffer Initiative for Population Health Policy at the University of Southern California, Los Angeles.

“Malpractice claim frequency has been falling pretty steadily for a while now, reflecting a number of factors including the widespread adoption of tort reform and other measures to shield physicians from malpractice risk,” Dr. Seabury said in an interview. “Interestingly, the decline seems greatest in the claims with lower potential stakes, as you see average indemnity holding flat or rising. Some of this likely reflects the unwillingness of attorneys to take cases with lower potential payouts, because of the high cost of litigating a malpractice case.”

While frequency went down, the cost to manage a legal claim went up, according to CRICO data. The price of defending a malpractice lawsuit rose an average of 3.5% annually over the 10-year period from $36,000 to $46,000. For cases that ended with no payment (indemnity) to plaintiffs, the cost to manage a case rose an average of 5% annually.

Dr. Michelle Mello

The upward trends in case management expenses are striking, particularly since the time to resolve cases has decreased, said Michelle Mello, PhD, a health research and policy professor at Stanford (Calif.) University. From 2007 to 2016, the average time to resolve a case dropped from 29 to 27 months, the CRICO report found.

“CRICO nods to disclosure and apology approaches as perhaps underlying the more encouraging trend in time to resolution, but it was surprising to me that such approaches have not translated into lower defense costs,” Dr. Mello said in an interview. “In particular, a lot is still being spent to manage cases that never result in a payment to the patient. My hope was that, as hospitals got better at communicating with patients about adverse events, including the fact that about three-quarters of them are not due to substandard care, there would be fewer claims involving such events and also less money spent dealing with such claims when they do arise.”

For cases that do end in payment, high payouts are on the rise. Cases that ended in payments of $1 million or more increased 4% over the 10-year time frame, while payments of $3 million to $11 million increased 7% annually, according to the CRICO report. Cases that ended in payment lower than $1 million dropped over the 10-year span.

The reasons behind increasing plaintiff payouts is uncertain, Dr. Seabury said.

“It’s hard to say exactly why high payouts are on the rise, as payout levels reflect a number of factors – [such as] economic damages, clinical severity, pain and suffering – that can be difficult to disentangle,” he said. “But it is probably concerning for doctors in the sense that, while claims are becoming less likely, when they do happen, it could be more catastrophic in the sense of having large damages that exceed the policy limit.”

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Lawsuits against physicians declined across virtually all specialties by more than a quarter over a 10-year span, but the cost to manage legal challenges went up, a recent analysis finds.

From 2007 to 2016, the rate of claims dropped by 27% per 100 doctors from 5.1 to 3.7, according to a review of 124,000 cases by CRICO Strategies, a division of CRICO, the medical liability insurance provider for the Harvard medical community. CRICO’s database of claims contains about 30% of legal cases filed against health providers across the U.S.

For internists, the rate of lawsuits decreased by 35% between 2007 and 2016, according to CRICO data provided to MDedge News. Ob.gyns. saw a 44% drop in claims over the 10-year period, and surgeons experienced a 23% rate decrease. The analysis did not break down the rate of claims by other single subspecialists. Claims decreased by a combined 29% for cardiologists, dermatologists, endocrinologists, family physicians, gastroenterologists, hematologists/oncologists, hospitalists, infectious disease specialists, internists, nephrologists, neurologists, pulmonologists, and rheumatologists/immunologists, according to the report published in February 2019 on CRICO’s website.

The findings are consistent with prior research on claim trends, said Seth Seabury, PhD, a medical liability researcher and director of the Keck-Schaeffer Initiative for Population Health Policy at the University of Southern California, Los Angeles.

“Malpractice claim frequency has been falling pretty steadily for a while now, reflecting a number of factors including the widespread adoption of tort reform and other measures to shield physicians from malpractice risk,” Dr. Seabury said in an interview. “Interestingly, the decline seems greatest in the claims with lower potential stakes, as you see average indemnity holding flat or rising. Some of this likely reflects the unwillingness of attorneys to take cases with lower potential payouts, because of the high cost of litigating a malpractice case.”

While frequency went down, the cost to manage a legal claim went up, according to CRICO data. The price of defending a malpractice lawsuit rose an average of 3.5% annually over the 10-year period from $36,000 to $46,000. For cases that ended with no payment (indemnity) to plaintiffs, the cost to manage a case rose an average of 5% annually.

Dr. Michelle Mello

The upward trends in case management expenses are striking, particularly since the time to resolve cases has decreased, said Michelle Mello, PhD, a health research and policy professor at Stanford (Calif.) University. From 2007 to 2016, the average time to resolve a case dropped from 29 to 27 months, the CRICO report found.

“CRICO nods to disclosure and apology approaches as perhaps underlying the more encouraging trend in time to resolution, but it was surprising to me that such approaches have not translated into lower defense costs,” Dr. Mello said in an interview. “In particular, a lot is still being spent to manage cases that never result in a payment to the patient. My hope was that, as hospitals got better at communicating with patients about adverse events, including the fact that about three-quarters of them are not due to substandard care, there would be fewer claims involving such events and also less money spent dealing with such claims when they do arise.”

For cases that do end in payment, high payouts are on the rise. Cases that ended in payments of $1 million or more increased 4% over the 10-year time frame, while payments of $3 million to $11 million increased 7% annually, according to the CRICO report. Cases that ended in payment lower than $1 million dropped over the 10-year span.

The reasons behind increasing plaintiff payouts is uncertain, Dr. Seabury said.

“It’s hard to say exactly why high payouts are on the rise, as payout levels reflect a number of factors – [such as] economic damages, clinical severity, pain and suffering – that can be difficult to disentangle,” he said. “But it is probably concerning for doctors in the sense that, while claims are becoming less likely, when they do happen, it could be more catastrophic in the sense of having large damages that exceed the policy limit.”

Lawsuits against physicians declined across virtually all specialties by more than a quarter over a 10-year span, but the cost to manage legal challenges went up, a recent analysis finds.

From 2007 to 2016, the rate of claims dropped by 27% per 100 doctors from 5.1 to 3.7, according to a review of 124,000 cases by CRICO Strategies, a division of CRICO, the medical liability insurance provider for the Harvard medical community. CRICO’s database of claims contains about 30% of legal cases filed against health providers across the U.S.

For internists, the rate of lawsuits decreased by 35% between 2007 and 2016, according to CRICO data provided to MDedge News. Ob.gyns. saw a 44% drop in claims over the 10-year period, and surgeons experienced a 23% rate decrease. The analysis did not break down the rate of claims by other single subspecialists. Claims decreased by a combined 29% for cardiologists, dermatologists, endocrinologists, family physicians, gastroenterologists, hematologists/oncologists, hospitalists, infectious disease specialists, internists, nephrologists, neurologists, pulmonologists, and rheumatologists/immunologists, according to the report published in February 2019 on CRICO’s website.

The findings are consistent with prior research on claim trends, said Seth Seabury, PhD, a medical liability researcher and director of the Keck-Schaeffer Initiative for Population Health Policy at the University of Southern California, Los Angeles.

“Malpractice claim frequency has been falling pretty steadily for a while now, reflecting a number of factors including the widespread adoption of tort reform and other measures to shield physicians from malpractice risk,” Dr. Seabury said in an interview. “Interestingly, the decline seems greatest in the claims with lower potential stakes, as you see average indemnity holding flat or rising. Some of this likely reflects the unwillingness of attorneys to take cases with lower potential payouts, because of the high cost of litigating a malpractice case.”

While frequency went down, the cost to manage a legal claim went up, according to CRICO data. The price of defending a malpractice lawsuit rose an average of 3.5% annually over the 10-year period from $36,000 to $46,000. For cases that ended with no payment (indemnity) to plaintiffs, the cost to manage a case rose an average of 5% annually.

Dr. Michelle Mello

The upward trends in case management expenses are striking, particularly since the time to resolve cases has decreased, said Michelle Mello, PhD, a health research and policy professor at Stanford (Calif.) University. From 2007 to 2016, the average time to resolve a case dropped from 29 to 27 months, the CRICO report found.

“CRICO nods to disclosure and apology approaches as perhaps underlying the more encouraging trend in time to resolution, but it was surprising to me that such approaches have not translated into lower defense costs,” Dr. Mello said in an interview. “In particular, a lot is still being spent to manage cases that never result in a payment to the patient. My hope was that, as hospitals got better at communicating with patients about adverse events, including the fact that about three-quarters of them are not due to substandard care, there would be fewer claims involving such events and also less money spent dealing with such claims when they do arise.”

For cases that do end in payment, high payouts are on the rise. Cases that ended in payments of $1 million or more increased 4% over the 10-year time frame, while payments of $3 million to $11 million increased 7% annually, according to the CRICO report. Cases that ended in payment lower than $1 million dropped over the 10-year span.

The reasons behind increasing plaintiff payouts is uncertain, Dr. Seabury said.

“It’s hard to say exactly why high payouts are on the rise, as payout levels reflect a number of factors – [such as] economic damages, clinical severity, pain and suffering – that can be difficult to disentangle,” he said. “But it is probably concerning for doctors in the sense that, while claims are becoming less likely, when they do happen, it could be more catastrophic in the sense of having large damages that exceed the policy limit.”

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Human papillomavirus in 2019: An update on cervical cancer prevention and screening guidelines

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Wed, 04/24/2019 - 12:36
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Human papillomavirus in 2019: An update on cervical cancer prevention and screening guidelines

About 12% of women worldwide are infected with human papillomavirus (HPV).1 Persistent HPV infection with high-risk strains such as HPV 6, 11, 16, and 18 cause nearly all cases of cervical cancer and some anal, vaginal, penile, and oropharyngeal cancers.2 An estimated 13,000 cases of invasive cervical cancer will be diagnosed this year in the United States alone.3

Up to 70% of HPV-related cervical cancer cases can be prevented with vaccination. A number of changes have been made to the vaccination schedule within the past few years—patients younger than 15 need only 2 rather than 3 doses, and the vaccine itself can be used in adults up to age 45.

Vaccination and routine cervical cancer screening are both necessary to prevent this disease3 along with effective family and patient counseling. Here, we discuss the most up-to-date HPV vaccination recommendations, current cervical cancer screening guidelines, counseling techniques that increase vaccination acceptance rates, and follow-up protocols for abnormal cervical cancer screening results.

TYPES OF HPV VACCINES

HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts.4 The US Food and Drug Administration (FDA) has approved 3 HPV vaccines:

  • Gardasil 9 targets HPV types 6, 11, 16, and 18 along with 31, 33, 45, 52, 58—these cause 90% of cervical cancer cases and most cases of genital warts5—making it the most effective vaccine available; Gardasil 9 is the only HPV vaccine currently available in the United States
  • The bivalent vaccine (Cervarix) targeted HPV 16 and 18 only, and was discontinued in the United States in 2016
  • The quadrivalent HPV vaccine (Gardasil) targeted HPV 16 and 18 as well as 6 and 11, which cause most cases of genital warts; the last available doses in the United States expired in May 2017; it has been replaced by Gardasil 9.

The incidence of cervical cancer in the United States dropped 29% among 15- to 24-year-olds from 2003–2006 when HPV vaccination first started to 2011–2014.6

VACCINE DOSING RECOMMENDATIONS FOR PRIMARY PREVENTION

HPV vaccination timeline, male and female

The Advisory Committee on Immunization Practices (ACIP) revised its HPV vaccine schedule in 2016, when it decreased the necessary doses from 3 to 2 for patients under age 15 and addressed the needs of special patient populations.7 In late 2018, the FDA approved the use of the vaccine in men and women up to age 45. However, no change in guidelines have yet been made (Table 1).

In females, the ACIP recommends starting HPV vaccination at age 11 or 12, but it can be given as early as age 9. A 2-dose schedule is recommended for the 9-valent vaccine before the patient’s 15th birthday (the second dose 6 to 12 months after the first).7 For females who initiate HPV vaccination between ages 15 and 45, a 3-dose schedule is necessary (at 0, 1 to 2, and 6 months).7,8

The change to a 2-dose schedule was prompted by an evaluation of girls ages 9 to 13 randomized to receive either a 2- or 3-dose schedule. Antibody responses with a 2-dose schedule were not inferior to those of young women (ages 16 to 26) who received all 3 doses.9 The geometric mean titer ratios remained noninferior throughout the study period of 36 months.

However, a loss of noninferiority was noted for HPV-18 by 24 months and for HPV-6 by 36 months.9 Thus, further studies are needed to understand the duration of protection with a 2-dose schedule. Nevertheless, decreasing the number of doses makes it a more convenient and cost-effective option for many families.

The recommendations are the same for males except for one notable difference: in males ages 21 to 26, vaccination is not routinely recommended by the ACIP, but rather it is considered a “permissive use” recommendation: ie, the vaccine should be offered and final decisions on administration be made after individualized discussion with the patient.10 Permissive-use status also means the vaccine may not be covered by health insurance. Even though the vaccine is now available to men and women until age 45, many insurance plans do not cover it after age 26.

Children of either sex with a history of sexual abuse should receive their first vaccine dose beginning at age 9.7

Immunocompromised patients should follow the 3-dose schedule regardless of their sex or the age when vaccination was initiated.10

For transgender patients and for men not previously vaccinated who have sex with men, the 3-dose schedule vaccine should be given by the age of 26 (this is a routine recommendation, not a permissive one).8

 

 

CHALLENGES OF VACCINATION

Effective patient and family counseling is important. Even though the first HPV vaccine was approved in 2006, only 34.9% of US adolescents were fully vaccinated by 2015. This was in part because providers did not recommend it, were unfamiliar with it, or had concerns about its safety,11,12 and in part because some parents refused it.

The physician must address any myths regarding HPV vaccination and ensure that parents and patients understand that HPV vaccine is safe and effective. Studies have shown that with high-quality recommendations (ie, the care provider strongly endorses the HPV vaccine, encourages same-day vaccination, and discusses cancer prevention), patients are 9 times more likely to start the HPV vaccination schedule and 3 times more likely to follow through with subsequent doses.13

Providing good family and patient education does not necessarily require spending more counseling time. A recent study showed that spending less time discussing the HPV vaccine can lead to better vaccine coverage.14 The study compared parent HPV vaccine counseling techniques and found that simply informing patients and their families that the HPV vaccine was due was associated with a higher vaccine acceptance rate than inviting conversations about it.14 When providers announced that the vaccine was due, assuming the parents were ready to vaccinate, there was a 5.4% increase in HPV vaccination coverage.14

Facts about the human papillomavirus (HPV) vaccine

Conversely, physicians who engaged parents in open-ended discussions about the HPV vaccine did not improve HPV vaccination coverage.14 The authors suggested that providers approach HPV vaccination as if they were counseling patients and families about the need to avoid second-hand smoke or the need to use car seats. If parents or patients resist the presumptive announcement approach, expanded counseling and shared decision-making are appropriate. This includes addressing misconceptions that parents and patients may have about the HPV vaccine. The American Cancer Society lists 8 facts to reference (Table 2).15

SECONDARY PREVENTION: CERVICAL CANCER SCREENING

Since the introduction of the Papanicolaou (Pap) test, US cervical cancer incidence rates have decreased by more than 60%.16 Because almost all cervical cancer is preventable with proper screening, all women ages 21 to 65 should be screened.

Cervical cancer screening recommendations, ACOG, ASCCP, USPSTF

Currently, there are 3 options available for cervical cancer screening: the Pap-only test, the Pap-HPV cotest, and the high-risk HPV-only test (Table 3). The latter 2 options detect high-risk HPV genotypes.

Several organizations have screening algorithms that recommend when to use these tests, but the 3 that shape today’s standard of care in cervical cancer screening come from the American College of Obstetricians and Gynecologists (ACOG), the American Society for Colposcopy and Cervical Pathology (ASCCP), and US Preventive Services Task Force (USPSTF).17–19

Pap-only testing is performed every 3 years to screen for cervical neoplasia that might indicate premalignancy.

Pap-HPV cotesting is performed every 5 years in women older than 30 with past normal screening. Until 2018, all 3 organizations recommended cotesting as the preferred screening algorithm for women ages 30 to 65.17–19 Patients with a history of abnormal test results require more frequent testing as recommended by the ASCCP.18

The high-risk HPV-only test utilizes real-time polymerase chain reaction to detect HPV 16, HPV 18, and 12 other HPV genotypes. Only 2 tests are approved by the FDA as stand-alone cervical cancer screening tests—the Roche Cobas HPV test approved in 2014 and the Becton Dickinson Onclarity HPV assay approved in 2018. Other HPV tests that are used in a cotesting strategy should not be used for high-risk HPV-only testing because their performance characteristics may differ.

In 2015, the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study showed that 1 round of high-risk HPV-only screening for women older than 25 was more sensitive than Pap-only or cotesting for stage 3 cervical intraepithelial neoplasia or more severe disease (after 3 years of follow-up).20 Current guidelines from ASCCP18 and ACOG17 state that the high-risk HPV test can be repeated every 3 years (when used to screen by itself) if the woman is older than 25 and has had a normal test result.

Screening for only high-risk human papillomavirus (HPV) genotypes
Figure 1.

If the HPV test result is positive for high-risk HPV 16 or 18 genotypes, then immediate colposcopy is indicated; women who test positive for one of the other 12 high-risk subtypes will need to undergo a Pap test to determine the appropriate follow-up (Figure 1).18,21

In 2018, the USPSTF updated its recommendations, noting that for women age 30 to 65, Pap-only testing every 3 years, cotesting every 5 years, or high-risk HPV-only testing every 5 years are all appropriate screening strategies, with the Pap-only or high-risk HPV-only screenings being preferred.19 This is in contrast to ACOG and ASCCP recommendations for cotesting every 5 years, with alternative options of Pap-only or HPV-only testing being done every 3 years.17,18

 

 

Is there a best screening protocol?

The USPSTF reviewed large randomized and observational studies to summarize the effectiveness of the 3 screening strategies and commissioned a decision analysis model to compare the risks, benefits, and costs of the 3 screening algorithms. The guideline statement notes both cotesting and high-risk HPV testing offer similar cancer detection rates: each prevents 1 additional cancer per 1,000 women screened as opposed to Pap-only testing.19

Also, tests that incorporate high-risk HPV screening may offer better detection of cervical adenocarcinoma (which has a worse prognosis than the more common squamous cell carcinoma type). However, both HPV-based screening strategies are more likely to require additional colposcopies for follow-up than Pap-only screening (1,630 colposcopies required for each cancer prevented with high-risk HPV alone, 1,635 with cotesting). Colposcopy is a simple office procedure that causes minimal discomfort to the patient.

The USPSTF guideline also differs in the recommended frequency of high-risk HPV-only testing; a high-risk HPV result should be repeated every 5 years if normal (as opposed to every 3 years as recommended by ACOG and ASCCP).19 The 5-year recommendation is based on analysis modeling, which suggests that performing high-risk HPV-only testing more frequently is unlikely to improve detection rates but will increase the number of screening tests and colposcopies.19

No trial has directly compared cotesting with high-risk HPV testing for more than 2 rounds of screening. The updated USPSTF recommendations are based on modeling estimates and expert opinion, which assesses cost and benefit vs harm in the long term. Also, no high-risk HPV test is currently FDA-approved for every-5-year screening when used by itself.

All 3 cervical cancer screening methods provide highly effective cancer prevention, so it is important for providers to choose the strategy that best fits their practice. The most critical aspect of screening is getting all women screened, no matter which method is used.

It is critical to remember that the screening intervals are intended for patients without symptoms. Those who have new concerns such as bleeding should have a diagnostic Pap done to evaluate their symptoms.

Follow-up of abnormal results

Regardless of the pathway chosen, appropriate follow-up of any abnormal test result is critical to the early detection of cancer. Established follow-up guidelines exist,22,23 but accessing this information can be difficult for the busy clinician. The ASCCP has a mobile phone application that outlines the action steps corresponding to the patient’s age and results of any combination of Pap or HPV testing. The app also includes the best screening algorithms for a particular patient.24

All guidelines agree that cervical cancer screening should start at age 21, regardless of HPV vaccination status or age of sexual initiation.17,18,25 Screening can be discontinued at age 65 for women with normal screening results in the prior decade (3 consecutive negative Pap results or 2 consecutive negative cotest results).23

For women who have had a total hysterectomy and no history of cervical neoplasia, screening should be stopped immediately after the procedure. However, several high-risk groups of women will need continued screening past the age of 65, or after a hysterectomy.

For a woman with a history of stage 2 cervical intraepithelial neoplasia or higher grade lesions, routine screening is continued for an additional 20 years, even if she is over age 65. Pap-only testing every 3 years is acceptable, because the role of HPV testing is unclear after hysterectomy.23 Prior guidelines suggested annual screening in these patients, so the change to every 3 years is notable. Many gynecologic oncologists will recommend that women with a history of cervical cancer continue annual screening indefinitely.

Within the first 2 to 3 years after treatment for high-grade dysplastic changes, annual follow-up is done by the gynecologic oncology team. Providers who offer follow-up during this time frame should keep in communication with the oncology team to ensure appropriate, individualized care. These recommendations are based on expert opinion, so variations in clinical practice may be seen.

Women infected with the human immunodeficiency virus can have Pap-only testing every 3 years, after a series of 3 normal annual Pap results.26 But screening does not stop at age 65.23,26 For patients who are immunosuppressed or have a history of diethylstilbestrol exposure, screening should be done annually indefinitely.23

References
  1. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010; 202(12):1789–1799. doi:10.1086/657321
  2. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancer attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012; 13(6):607–615. doi:10.1016/S1470-2045(12)70137-7
  3. American Cancer Society. Key statistics for cervical cancer. www.cancer.org/cancer/cervical-cancer/about/key-statistics.html. Accessed February 14, 2019.
  4. Thaxton L, Waxman AG. Cervical cancer prevention: immunization and screening 2015. Med Clin North Am 2015; 99(3):469–477. doi:10.1016/j.mcna.2015.01.003
  5. McNamara M, Batur P, Walsh JME, Johnson KM. HPV update: vaccination, screening, and associated disease. J Gen Intern Med 2016; 31(11):1360–1366. doi:10.1007/s11606-016-3725-z
  6. Guo F, Cofie LE, Berenson AB. Cervical cancer incidence in young US females after human papillomavirus vaccine introduction. Am J Prev Med 2018; 55(2):197–204. doi:10.1016/j.amepre.2018.03.013
  7. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016; 65(49):1405–1408. doi:10.15585/mmwr.mm6549a5
  8. Centers for Disease Control and Prevention (CDC). Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV vaccine Information for persons who started an HPV vaccination series with quadrivalent or bivalent HPV vaccine. www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf. Accessed February 14, 2019.
  9. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309(17):1793–1802. doi:10.1001/jama.2013.1625
  10. Markowitz LE, Dunne EF, Saraiya M, et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63(RR-05):1–30. pmid:25167164
  11. Thompson EL, Rosen BL, Vamos CA, Kadono M, Daley EM. Human papillomavirus vaccination: what are the reasons for nonvaccination among US adolescents? J Adolesc Health 2017; 61(3):288–293. doi:10.1016/j.jadohealth.2017.05.015
  12. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep 2016; 65(33):850–858. doi:10.15585/mmwr.mm6533a4
  13. Gilkey MB, Calo WA, Moss JL, Shah PD, Marciniak MW, Brewer NT. Provider communication and HPV vaccination: The impact of recommendation quality. Vaccine 2016; 34(9):1187–1192. doi:10.1016/j.vaccine.2016.01.023
  14. Brewer NT, Hall ME, Malo TL, Gilkey MB, Quinn B, Lathren C. Announcements versus conversations to improve HPV vaccination coverage: a randomized trial. Pediatrics 2017; 139(1):e20161764. doi:10.1542/peds.2016-1764
  15. American Cancer Society. HPV vaccine facts. www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/hpv-vaccine-facts-and-fears.html. Accessed February 14, 2019.
  16. National Cancer Institute; Chasan R, Manrow R. Cervical cancer. https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76. Accessed February 14, 2019.
  17. The American College of Obstetricians and Gynecologists (ACOG). Frequently asked questions. Cervical cancer screening. www.acog.org/Patients/FAQs/Cervical-Cancer-Screening. Accessed February 14, 2019.
  18. Saslow D, Solomon D, Lawson HW, et al; American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol 2012; 137(4):516–542. doi:10.1309/AJCPTGD94EVRSJCG
  19. US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 320(7):674–686. doi:10.1001/jama.2018.10897
  20. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015; 136(2):189–197. doi:10.1016/j.ygyno.2014.11.076
  21. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol 2015; 125(2):330–337. doi:10.1097/AOG.0000000000000669
  22. Massad LS, Einstein MH, Huh WK, et al; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013; 121(4):829–846. doi:10.1097/AOG.0b013e3182883a34
  23. Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: cervical cancer screening and prevention. Obstet Gynecol 2016; 128(4):e111–e130. doi:10.1097/AOG.0000000000001708
  24. ASCCP. Mobile app. http://www.asccp.org/store-detail2/asccp-mobile-app. Accessed February 14, 2019.
  25. USPSTF. Draft recommendation: cervical cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Accessed February 14, 2019.
  26. Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE; National Institutes of Health; Centers for Disease Control and Prevention; HIV Medicine Association of the Infectious Diseases Society of America. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58(9):1308–1311. doi:10.1093/cid/ciu094
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Salina Zhang, BS
Case Western Reserve University School of Medicine, Cleveland, OH

Pelin Batur, MD, FACP, NCMP, CCD
Department of Obstetrics and Gynecology, Women’s Health Institute, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH; Deputy Editor, Cleveland Clinic Journal of Medicine, Working Group Member of the US Cervical Cancer Screening Risk-Based Management Guidelines Committee

Address: Pelin Batur, MD, FACP, NCMP, CCD, Department of Obstetrics and Gynecology, Women’s Health Institute, A81, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

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human papillomavirus, HPV, cervical cancer, screening, immunization, vaccination, HPV vaccine, Gardasil, Papanicolaou test, Pap test, HPV test, screening, Salina Zhang, Pelin Batur
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Salina Zhang, BS
Case Western Reserve University School of Medicine, Cleveland, OH

Pelin Batur, MD, FACP, NCMP, CCD
Department of Obstetrics and Gynecology, Women’s Health Institute, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH; Deputy Editor, Cleveland Clinic Journal of Medicine, Working Group Member of the US Cervical Cancer Screening Risk-Based Management Guidelines Committee

Address: Pelin Batur, MD, FACP, NCMP, CCD, Department of Obstetrics and Gynecology, Women’s Health Institute, A81, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

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Salina Zhang, BS
Case Western Reserve University School of Medicine, Cleveland, OH

Pelin Batur, MD, FACP, NCMP, CCD
Department of Obstetrics and Gynecology, Women’s Health Institute, Cleveland Clinic; Associate Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH; Deputy Editor, Cleveland Clinic Journal of Medicine, Working Group Member of the US Cervical Cancer Screening Risk-Based Management Guidelines Committee

Address: Pelin Batur, MD, FACP, NCMP, CCD, Department of Obstetrics and Gynecology, Women’s Health Institute, A81, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

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Related Articles

About 12% of women worldwide are infected with human papillomavirus (HPV).1 Persistent HPV infection with high-risk strains such as HPV 6, 11, 16, and 18 cause nearly all cases of cervical cancer and some anal, vaginal, penile, and oropharyngeal cancers.2 An estimated 13,000 cases of invasive cervical cancer will be diagnosed this year in the United States alone.3

Up to 70% of HPV-related cervical cancer cases can be prevented with vaccination. A number of changes have been made to the vaccination schedule within the past few years—patients younger than 15 need only 2 rather than 3 doses, and the vaccine itself can be used in adults up to age 45.

Vaccination and routine cervical cancer screening are both necessary to prevent this disease3 along with effective family and patient counseling. Here, we discuss the most up-to-date HPV vaccination recommendations, current cervical cancer screening guidelines, counseling techniques that increase vaccination acceptance rates, and follow-up protocols for abnormal cervical cancer screening results.

TYPES OF HPV VACCINES

HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts.4 The US Food and Drug Administration (FDA) has approved 3 HPV vaccines:

  • Gardasil 9 targets HPV types 6, 11, 16, and 18 along with 31, 33, 45, 52, 58—these cause 90% of cervical cancer cases and most cases of genital warts5—making it the most effective vaccine available; Gardasil 9 is the only HPV vaccine currently available in the United States
  • The bivalent vaccine (Cervarix) targeted HPV 16 and 18 only, and was discontinued in the United States in 2016
  • The quadrivalent HPV vaccine (Gardasil) targeted HPV 16 and 18 as well as 6 and 11, which cause most cases of genital warts; the last available doses in the United States expired in May 2017; it has been replaced by Gardasil 9.

The incidence of cervical cancer in the United States dropped 29% among 15- to 24-year-olds from 2003–2006 when HPV vaccination first started to 2011–2014.6

VACCINE DOSING RECOMMENDATIONS FOR PRIMARY PREVENTION

HPV vaccination timeline, male and female

The Advisory Committee on Immunization Practices (ACIP) revised its HPV vaccine schedule in 2016, when it decreased the necessary doses from 3 to 2 for patients under age 15 and addressed the needs of special patient populations.7 In late 2018, the FDA approved the use of the vaccine in men and women up to age 45. However, no change in guidelines have yet been made (Table 1).

In females, the ACIP recommends starting HPV vaccination at age 11 or 12, but it can be given as early as age 9. A 2-dose schedule is recommended for the 9-valent vaccine before the patient’s 15th birthday (the second dose 6 to 12 months after the first).7 For females who initiate HPV vaccination between ages 15 and 45, a 3-dose schedule is necessary (at 0, 1 to 2, and 6 months).7,8

The change to a 2-dose schedule was prompted by an evaluation of girls ages 9 to 13 randomized to receive either a 2- or 3-dose schedule. Antibody responses with a 2-dose schedule were not inferior to those of young women (ages 16 to 26) who received all 3 doses.9 The geometric mean titer ratios remained noninferior throughout the study period of 36 months.

However, a loss of noninferiority was noted for HPV-18 by 24 months and for HPV-6 by 36 months.9 Thus, further studies are needed to understand the duration of protection with a 2-dose schedule. Nevertheless, decreasing the number of doses makes it a more convenient and cost-effective option for many families.

The recommendations are the same for males except for one notable difference: in males ages 21 to 26, vaccination is not routinely recommended by the ACIP, but rather it is considered a “permissive use” recommendation: ie, the vaccine should be offered and final decisions on administration be made after individualized discussion with the patient.10 Permissive-use status also means the vaccine may not be covered by health insurance. Even though the vaccine is now available to men and women until age 45, many insurance plans do not cover it after age 26.

Children of either sex with a history of sexual abuse should receive their first vaccine dose beginning at age 9.7

Immunocompromised patients should follow the 3-dose schedule regardless of their sex or the age when vaccination was initiated.10

For transgender patients and for men not previously vaccinated who have sex with men, the 3-dose schedule vaccine should be given by the age of 26 (this is a routine recommendation, not a permissive one).8

 

 

CHALLENGES OF VACCINATION

Effective patient and family counseling is important. Even though the first HPV vaccine was approved in 2006, only 34.9% of US adolescents were fully vaccinated by 2015. This was in part because providers did not recommend it, were unfamiliar with it, or had concerns about its safety,11,12 and in part because some parents refused it.

The physician must address any myths regarding HPV vaccination and ensure that parents and patients understand that HPV vaccine is safe and effective. Studies have shown that with high-quality recommendations (ie, the care provider strongly endorses the HPV vaccine, encourages same-day vaccination, and discusses cancer prevention), patients are 9 times more likely to start the HPV vaccination schedule and 3 times more likely to follow through with subsequent doses.13

Providing good family and patient education does not necessarily require spending more counseling time. A recent study showed that spending less time discussing the HPV vaccine can lead to better vaccine coverage.14 The study compared parent HPV vaccine counseling techniques and found that simply informing patients and their families that the HPV vaccine was due was associated with a higher vaccine acceptance rate than inviting conversations about it.14 When providers announced that the vaccine was due, assuming the parents were ready to vaccinate, there was a 5.4% increase in HPV vaccination coverage.14

Facts about the human papillomavirus (HPV) vaccine

Conversely, physicians who engaged parents in open-ended discussions about the HPV vaccine did not improve HPV vaccination coverage.14 The authors suggested that providers approach HPV vaccination as if they were counseling patients and families about the need to avoid second-hand smoke or the need to use car seats. If parents or patients resist the presumptive announcement approach, expanded counseling and shared decision-making are appropriate. This includes addressing misconceptions that parents and patients may have about the HPV vaccine. The American Cancer Society lists 8 facts to reference (Table 2).15

SECONDARY PREVENTION: CERVICAL CANCER SCREENING

Since the introduction of the Papanicolaou (Pap) test, US cervical cancer incidence rates have decreased by more than 60%.16 Because almost all cervical cancer is preventable with proper screening, all women ages 21 to 65 should be screened.

Cervical cancer screening recommendations, ACOG, ASCCP, USPSTF

Currently, there are 3 options available for cervical cancer screening: the Pap-only test, the Pap-HPV cotest, and the high-risk HPV-only test (Table 3). The latter 2 options detect high-risk HPV genotypes.

Several organizations have screening algorithms that recommend when to use these tests, but the 3 that shape today’s standard of care in cervical cancer screening come from the American College of Obstetricians and Gynecologists (ACOG), the American Society for Colposcopy and Cervical Pathology (ASCCP), and US Preventive Services Task Force (USPSTF).17–19

Pap-only testing is performed every 3 years to screen for cervical neoplasia that might indicate premalignancy.

Pap-HPV cotesting is performed every 5 years in women older than 30 with past normal screening. Until 2018, all 3 organizations recommended cotesting as the preferred screening algorithm for women ages 30 to 65.17–19 Patients with a history of abnormal test results require more frequent testing as recommended by the ASCCP.18

The high-risk HPV-only test utilizes real-time polymerase chain reaction to detect HPV 16, HPV 18, and 12 other HPV genotypes. Only 2 tests are approved by the FDA as stand-alone cervical cancer screening tests—the Roche Cobas HPV test approved in 2014 and the Becton Dickinson Onclarity HPV assay approved in 2018. Other HPV tests that are used in a cotesting strategy should not be used for high-risk HPV-only testing because their performance characteristics may differ.

In 2015, the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study showed that 1 round of high-risk HPV-only screening for women older than 25 was more sensitive than Pap-only or cotesting for stage 3 cervical intraepithelial neoplasia or more severe disease (after 3 years of follow-up).20 Current guidelines from ASCCP18 and ACOG17 state that the high-risk HPV test can be repeated every 3 years (when used to screen by itself) if the woman is older than 25 and has had a normal test result.

Screening for only high-risk human papillomavirus (HPV) genotypes
Figure 1.

If the HPV test result is positive for high-risk HPV 16 or 18 genotypes, then immediate colposcopy is indicated; women who test positive for one of the other 12 high-risk subtypes will need to undergo a Pap test to determine the appropriate follow-up (Figure 1).18,21

In 2018, the USPSTF updated its recommendations, noting that for women age 30 to 65, Pap-only testing every 3 years, cotesting every 5 years, or high-risk HPV-only testing every 5 years are all appropriate screening strategies, with the Pap-only or high-risk HPV-only screenings being preferred.19 This is in contrast to ACOG and ASCCP recommendations for cotesting every 5 years, with alternative options of Pap-only or HPV-only testing being done every 3 years.17,18

 

 

Is there a best screening protocol?

The USPSTF reviewed large randomized and observational studies to summarize the effectiveness of the 3 screening strategies and commissioned a decision analysis model to compare the risks, benefits, and costs of the 3 screening algorithms. The guideline statement notes both cotesting and high-risk HPV testing offer similar cancer detection rates: each prevents 1 additional cancer per 1,000 women screened as opposed to Pap-only testing.19

Also, tests that incorporate high-risk HPV screening may offer better detection of cervical adenocarcinoma (which has a worse prognosis than the more common squamous cell carcinoma type). However, both HPV-based screening strategies are more likely to require additional colposcopies for follow-up than Pap-only screening (1,630 colposcopies required for each cancer prevented with high-risk HPV alone, 1,635 with cotesting). Colposcopy is a simple office procedure that causes minimal discomfort to the patient.

The USPSTF guideline also differs in the recommended frequency of high-risk HPV-only testing; a high-risk HPV result should be repeated every 5 years if normal (as opposed to every 3 years as recommended by ACOG and ASCCP).19 The 5-year recommendation is based on analysis modeling, which suggests that performing high-risk HPV-only testing more frequently is unlikely to improve detection rates but will increase the number of screening tests and colposcopies.19

No trial has directly compared cotesting with high-risk HPV testing for more than 2 rounds of screening. The updated USPSTF recommendations are based on modeling estimates and expert opinion, which assesses cost and benefit vs harm in the long term. Also, no high-risk HPV test is currently FDA-approved for every-5-year screening when used by itself.

All 3 cervical cancer screening methods provide highly effective cancer prevention, so it is important for providers to choose the strategy that best fits their practice. The most critical aspect of screening is getting all women screened, no matter which method is used.

It is critical to remember that the screening intervals are intended for patients without symptoms. Those who have new concerns such as bleeding should have a diagnostic Pap done to evaluate their symptoms.

Follow-up of abnormal results

Regardless of the pathway chosen, appropriate follow-up of any abnormal test result is critical to the early detection of cancer. Established follow-up guidelines exist,22,23 but accessing this information can be difficult for the busy clinician. The ASCCP has a mobile phone application that outlines the action steps corresponding to the patient’s age and results of any combination of Pap or HPV testing. The app also includes the best screening algorithms for a particular patient.24

All guidelines agree that cervical cancer screening should start at age 21, regardless of HPV vaccination status or age of sexual initiation.17,18,25 Screening can be discontinued at age 65 for women with normal screening results in the prior decade (3 consecutive negative Pap results or 2 consecutive negative cotest results).23

For women who have had a total hysterectomy and no history of cervical neoplasia, screening should be stopped immediately after the procedure. However, several high-risk groups of women will need continued screening past the age of 65, or after a hysterectomy.

For a woman with a history of stage 2 cervical intraepithelial neoplasia or higher grade lesions, routine screening is continued for an additional 20 years, even if she is over age 65. Pap-only testing every 3 years is acceptable, because the role of HPV testing is unclear after hysterectomy.23 Prior guidelines suggested annual screening in these patients, so the change to every 3 years is notable. Many gynecologic oncologists will recommend that women with a history of cervical cancer continue annual screening indefinitely.

Within the first 2 to 3 years after treatment for high-grade dysplastic changes, annual follow-up is done by the gynecologic oncology team. Providers who offer follow-up during this time frame should keep in communication with the oncology team to ensure appropriate, individualized care. These recommendations are based on expert opinion, so variations in clinical practice may be seen.

Women infected with the human immunodeficiency virus can have Pap-only testing every 3 years, after a series of 3 normal annual Pap results.26 But screening does not stop at age 65.23,26 For patients who are immunosuppressed or have a history of diethylstilbestrol exposure, screening should be done annually indefinitely.23

About 12% of women worldwide are infected with human papillomavirus (HPV).1 Persistent HPV infection with high-risk strains such as HPV 6, 11, 16, and 18 cause nearly all cases of cervical cancer and some anal, vaginal, penile, and oropharyngeal cancers.2 An estimated 13,000 cases of invasive cervical cancer will be diagnosed this year in the United States alone.3

Up to 70% of HPV-related cervical cancer cases can be prevented with vaccination. A number of changes have been made to the vaccination schedule within the past few years—patients younger than 15 need only 2 rather than 3 doses, and the vaccine itself can be used in adults up to age 45.

Vaccination and routine cervical cancer screening are both necessary to prevent this disease3 along with effective family and patient counseling. Here, we discuss the most up-to-date HPV vaccination recommendations, current cervical cancer screening guidelines, counseling techniques that increase vaccination acceptance rates, and follow-up protocols for abnormal cervical cancer screening results.

TYPES OF HPV VACCINES

HPV immunization can prevent up to 70% of cases of cervical cancer due to HPV as well as 90% of genital warts.4 The US Food and Drug Administration (FDA) has approved 3 HPV vaccines:

  • Gardasil 9 targets HPV types 6, 11, 16, and 18 along with 31, 33, 45, 52, 58—these cause 90% of cervical cancer cases and most cases of genital warts5—making it the most effective vaccine available; Gardasil 9 is the only HPV vaccine currently available in the United States
  • The bivalent vaccine (Cervarix) targeted HPV 16 and 18 only, and was discontinued in the United States in 2016
  • The quadrivalent HPV vaccine (Gardasil) targeted HPV 16 and 18 as well as 6 and 11, which cause most cases of genital warts; the last available doses in the United States expired in May 2017; it has been replaced by Gardasil 9.

The incidence of cervical cancer in the United States dropped 29% among 15- to 24-year-olds from 2003–2006 when HPV vaccination first started to 2011–2014.6

VACCINE DOSING RECOMMENDATIONS FOR PRIMARY PREVENTION

HPV vaccination timeline, male and female

The Advisory Committee on Immunization Practices (ACIP) revised its HPV vaccine schedule in 2016, when it decreased the necessary doses from 3 to 2 for patients under age 15 and addressed the needs of special patient populations.7 In late 2018, the FDA approved the use of the vaccine in men and women up to age 45. However, no change in guidelines have yet been made (Table 1).

In females, the ACIP recommends starting HPV vaccination at age 11 or 12, but it can be given as early as age 9. A 2-dose schedule is recommended for the 9-valent vaccine before the patient’s 15th birthday (the second dose 6 to 12 months after the first).7 For females who initiate HPV vaccination between ages 15 and 45, a 3-dose schedule is necessary (at 0, 1 to 2, and 6 months).7,8

The change to a 2-dose schedule was prompted by an evaluation of girls ages 9 to 13 randomized to receive either a 2- or 3-dose schedule. Antibody responses with a 2-dose schedule were not inferior to those of young women (ages 16 to 26) who received all 3 doses.9 The geometric mean titer ratios remained noninferior throughout the study period of 36 months.

However, a loss of noninferiority was noted for HPV-18 by 24 months and for HPV-6 by 36 months.9 Thus, further studies are needed to understand the duration of protection with a 2-dose schedule. Nevertheless, decreasing the number of doses makes it a more convenient and cost-effective option for many families.

The recommendations are the same for males except for one notable difference: in males ages 21 to 26, vaccination is not routinely recommended by the ACIP, but rather it is considered a “permissive use” recommendation: ie, the vaccine should be offered and final decisions on administration be made after individualized discussion with the patient.10 Permissive-use status also means the vaccine may not be covered by health insurance. Even though the vaccine is now available to men and women until age 45, many insurance plans do not cover it after age 26.

Children of either sex with a history of sexual abuse should receive their first vaccine dose beginning at age 9.7

Immunocompromised patients should follow the 3-dose schedule regardless of their sex or the age when vaccination was initiated.10

For transgender patients and for men not previously vaccinated who have sex with men, the 3-dose schedule vaccine should be given by the age of 26 (this is a routine recommendation, not a permissive one).8

 

 

CHALLENGES OF VACCINATION

Effective patient and family counseling is important. Even though the first HPV vaccine was approved in 2006, only 34.9% of US adolescents were fully vaccinated by 2015. This was in part because providers did not recommend it, were unfamiliar with it, or had concerns about its safety,11,12 and in part because some parents refused it.

The physician must address any myths regarding HPV vaccination and ensure that parents and patients understand that HPV vaccine is safe and effective. Studies have shown that with high-quality recommendations (ie, the care provider strongly endorses the HPV vaccine, encourages same-day vaccination, and discusses cancer prevention), patients are 9 times more likely to start the HPV vaccination schedule and 3 times more likely to follow through with subsequent doses.13

Providing good family and patient education does not necessarily require spending more counseling time. A recent study showed that spending less time discussing the HPV vaccine can lead to better vaccine coverage.14 The study compared parent HPV vaccine counseling techniques and found that simply informing patients and their families that the HPV vaccine was due was associated with a higher vaccine acceptance rate than inviting conversations about it.14 When providers announced that the vaccine was due, assuming the parents were ready to vaccinate, there was a 5.4% increase in HPV vaccination coverage.14

Facts about the human papillomavirus (HPV) vaccine

Conversely, physicians who engaged parents in open-ended discussions about the HPV vaccine did not improve HPV vaccination coverage.14 The authors suggested that providers approach HPV vaccination as if they were counseling patients and families about the need to avoid second-hand smoke or the need to use car seats. If parents or patients resist the presumptive announcement approach, expanded counseling and shared decision-making are appropriate. This includes addressing misconceptions that parents and patients may have about the HPV vaccine. The American Cancer Society lists 8 facts to reference (Table 2).15

SECONDARY PREVENTION: CERVICAL CANCER SCREENING

Since the introduction of the Papanicolaou (Pap) test, US cervical cancer incidence rates have decreased by more than 60%.16 Because almost all cervical cancer is preventable with proper screening, all women ages 21 to 65 should be screened.

Cervical cancer screening recommendations, ACOG, ASCCP, USPSTF

Currently, there are 3 options available for cervical cancer screening: the Pap-only test, the Pap-HPV cotest, and the high-risk HPV-only test (Table 3). The latter 2 options detect high-risk HPV genotypes.

Several organizations have screening algorithms that recommend when to use these tests, but the 3 that shape today’s standard of care in cervical cancer screening come from the American College of Obstetricians and Gynecologists (ACOG), the American Society for Colposcopy and Cervical Pathology (ASCCP), and US Preventive Services Task Force (USPSTF).17–19

Pap-only testing is performed every 3 years to screen for cervical neoplasia that might indicate premalignancy.

Pap-HPV cotesting is performed every 5 years in women older than 30 with past normal screening. Until 2018, all 3 organizations recommended cotesting as the preferred screening algorithm for women ages 30 to 65.17–19 Patients with a history of abnormal test results require more frequent testing as recommended by the ASCCP.18

The high-risk HPV-only test utilizes real-time polymerase chain reaction to detect HPV 16, HPV 18, and 12 other HPV genotypes. Only 2 tests are approved by the FDA as stand-alone cervical cancer screening tests—the Roche Cobas HPV test approved in 2014 and the Becton Dickinson Onclarity HPV assay approved in 2018. Other HPV tests that are used in a cotesting strategy should not be used for high-risk HPV-only testing because their performance characteristics may differ.

In 2015, the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study showed that 1 round of high-risk HPV-only screening for women older than 25 was more sensitive than Pap-only or cotesting for stage 3 cervical intraepithelial neoplasia or more severe disease (after 3 years of follow-up).20 Current guidelines from ASCCP18 and ACOG17 state that the high-risk HPV test can be repeated every 3 years (when used to screen by itself) if the woman is older than 25 and has had a normal test result.

Screening for only high-risk human papillomavirus (HPV) genotypes
Figure 1.

If the HPV test result is positive for high-risk HPV 16 or 18 genotypes, then immediate colposcopy is indicated; women who test positive for one of the other 12 high-risk subtypes will need to undergo a Pap test to determine the appropriate follow-up (Figure 1).18,21

In 2018, the USPSTF updated its recommendations, noting that for women age 30 to 65, Pap-only testing every 3 years, cotesting every 5 years, or high-risk HPV-only testing every 5 years are all appropriate screening strategies, with the Pap-only or high-risk HPV-only screenings being preferred.19 This is in contrast to ACOG and ASCCP recommendations for cotesting every 5 years, with alternative options of Pap-only or HPV-only testing being done every 3 years.17,18

 

 

Is there a best screening protocol?

The USPSTF reviewed large randomized and observational studies to summarize the effectiveness of the 3 screening strategies and commissioned a decision analysis model to compare the risks, benefits, and costs of the 3 screening algorithms. The guideline statement notes both cotesting and high-risk HPV testing offer similar cancer detection rates: each prevents 1 additional cancer per 1,000 women screened as opposed to Pap-only testing.19

Also, tests that incorporate high-risk HPV screening may offer better detection of cervical adenocarcinoma (which has a worse prognosis than the more common squamous cell carcinoma type). However, both HPV-based screening strategies are more likely to require additional colposcopies for follow-up than Pap-only screening (1,630 colposcopies required for each cancer prevented with high-risk HPV alone, 1,635 with cotesting). Colposcopy is a simple office procedure that causes minimal discomfort to the patient.

The USPSTF guideline also differs in the recommended frequency of high-risk HPV-only testing; a high-risk HPV result should be repeated every 5 years if normal (as opposed to every 3 years as recommended by ACOG and ASCCP).19 The 5-year recommendation is based on analysis modeling, which suggests that performing high-risk HPV-only testing more frequently is unlikely to improve detection rates but will increase the number of screening tests and colposcopies.19

No trial has directly compared cotesting with high-risk HPV testing for more than 2 rounds of screening. The updated USPSTF recommendations are based on modeling estimates and expert opinion, which assesses cost and benefit vs harm in the long term. Also, no high-risk HPV test is currently FDA-approved for every-5-year screening when used by itself.

All 3 cervical cancer screening methods provide highly effective cancer prevention, so it is important for providers to choose the strategy that best fits their practice. The most critical aspect of screening is getting all women screened, no matter which method is used.

It is critical to remember that the screening intervals are intended for patients without symptoms. Those who have new concerns such as bleeding should have a diagnostic Pap done to evaluate their symptoms.

Follow-up of abnormal results

Regardless of the pathway chosen, appropriate follow-up of any abnormal test result is critical to the early detection of cancer. Established follow-up guidelines exist,22,23 but accessing this information can be difficult for the busy clinician. The ASCCP has a mobile phone application that outlines the action steps corresponding to the patient’s age and results of any combination of Pap or HPV testing. The app also includes the best screening algorithms for a particular patient.24

All guidelines agree that cervical cancer screening should start at age 21, regardless of HPV vaccination status or age of sexual initiation.17,18,25 Screening can be discontinued at age 65 for women with normal screening results in the prior decade (3 consecutive negative Pap results or 2 consecutive negative cotest results).23

For women who have had a total hysterectomy and no history of cervical neoplasia, screening should be stopped immediately after the procedure. However, several high-risk groups of women will need continued screening past the age of 65, or after a hysterectomy.

For a woman with a history of stage 2 cervical intraepithelial neoplasia or higher grade lesions, routine screening is continued for an additional 20 years, even if she is over age 65. Pap-only testing every 3 years is acceptable, because the role of HPV testing is unclear after hysterectomy.23 Prior guidelines suggested annual screening in these patients, so the change to every 3 years is notable. Many gynecologic oncologists will recommend that women with a history of cervical cancer continue annual screening indefinitely.

Within the first 2 to 3 years after treatment for high-grade dysplastic changes, annual follow-up is done by the gynecologic oncology team. Providers who offer follow-up during this time frame should keep in communication with the oncology team to ensure appropriate, individualized care. These recommendations are based on expert opinion, so variations in clinical practice may be seen.

Women infected with the human immunodeficiency virus can have Pap-only testing every 3 years, after a series of 3 normal annual Pap results.26 But screening does not stop at age 65.23,26 For patients who are immunosuppressed or have a history of diethylstilbestrol exposure, screening should be done annually indefinitely.23

References
  1. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010; 202(12):1789–1799. doi:10.1086/657321
  2. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancer attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012; 13(6):607–615. doi:10.1016/S1470-2045(12)70137-7
  3. American Cancer Society. Key statistics for cervical cancer. www.cancer.org/cancer/cervical-cancer/about/key-statistics.html. Accessed February 14, 2019.
  4. Thaxton L, Waxman AG. Cervical cancer prevention: immunization and screening 2015. Med Clin North Am 2015; 99(3):469–477. doi:10.1016/j.mcna.2015.01.003
  5. McNamara M, Batur P, Walsh JME, Johnson KM. HPV update: vaccination, screening, and associated disease. J Gen Intern Med 2016; 31(11):1360–1366. doi:10.1007/s11606-016-3725-z
  6. Guo F, Cofie LE, Berenson AB. Cervical cancer incidence in young US females after human papillomavirus vaccine introduction. Am J Prev Med 2018; 55(2):197–204. doi:10.1016/j.amepre.2018.03.013
  7. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016; 65(49):1405–1408. doi:10.15585/mmwr.mm6549a5
  8. Centers for Disease Control and Prevention (CDC). Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV vaccine Information for persons who started an HPV vaccination series with quadrivalent or bivalent HPV vaccine. www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf. Accessed February 14, 2019.
  9. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309(17):1793–1802. doi:10.1001/jama.2013.1625
  10. Markowitz LE, Dunne EF, Saraiya M, et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63(RR-05):1–30. pmid:25167164
  11. Thompson EL, Rosen BL, Vamos CA, Kadono M, Daley EM. Human papillomavirus vaccination: what are the reasons for nonvaccination among US adolescents? J Adolesc Health 2017; 61(3):288–293. doi:10.1016/j.jadohealth.2017.05.015
  12. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep 2016; 65(33):850–858. doi:10.15585/mmwr.mm6533a4
  13. Gilkey MB, Calo WA, Moss JL, Shah PD, Marciniak MW, Brewer NT. Provider communication and HPV vaccination: The impact of recommendation quality. Vaccine 2016; 34(9):1187–1192. doi:10.1016/j.vaccine.2016.01.023
  14. Brewer NT, Hall ME, Malo TL, Gilkey MB, Quinn B, Lathren C. Announcements versus conversations to improve HPV vaccination coverage: a randomized trial. Pediatrics 2017; 139(1):e20161764. doi:10.1542/peds.2016-1764
  15. American Cancer Society. HPV vaccine facts. www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/hpv-vaccine-facts-and-fears.html. Accessed February 14, 2019.
  16. National Cancer Institute; Chasan R, Manrow R. Cervical cancer. https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76. Accessed February 14, 2019.
  17. The American College of Obstetricians and Gynecologists (ACOG). Frequently asked questions. Cervical cancer screening. www.acog.org/Patients/FAQs/Cervical-Cancer-Screening. Accessed February 14, 2019.
  18. Saslow D, Solomon D, Lawson HW, et al; American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol 2012; 137(4):516–542. doi:10.1309/AJCPTGD94EVRSJCG
  19. US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 320(7):674–686. doi:10.1001/jama.2018.10897
  20. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015; 136(2):189–197. doi:10.1016/j.ygyno.2014.11.076
  21. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol 2015; 125(2):330–337. doi:10.1097/AOG.0000000000000669
  22. Massad LS, Einstein MH, Huh WK, et al; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013; 121(4):829–846. doi:10.1097/AOG.0b013e3182883a34
  23. Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: cervical cancer screening and prevention. Obstet Gynecol 2016; 128(4):e111–e130. doi:10.1097/AOG.0000000000001708
  24. ASCCP. Mobile app. http://www.asccp.org/store-detail2/asccp-mobile-app. Accessed February 14, 2019.
  25. USPSTF. Draft recommendation: cervical cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Accessed February 14, 2019.
  26. Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE; National Institutes of Health; Centers for Disease Control and Prevention; HIV Medicine Association of the Infectious Diseases Society of America. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58(9):1308–1311. doi:10.1093/cid/ciu094
References
  1. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010; 202(12):1789–1799. doi:10.1086/657321
  2. de Martel C, Ferlay J, Franceschi S, et al. Global burden of cancer attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012; 13(6):607–615. doi:10.1016/S1470-2045(12)70137-7
  3. American Cancer Society. Key statistics for cervical cancer. www.cancer.org/cancer/cervical-cancer/about/key-statistics.html. Accessed February 14, 2019.
  4. Thaxton L, Waxman AG. Cervical cancer prevention: immunization and screening 2015. Med Clin North Am 2015; 99(3):469–477. doi:10.1016/j.mcna.2015.01.003
  5. McNamara M, Batur P, Walsh JME, Johnson KM. HPV update: vaccination, screening, and associated disease. J Gen Intern Med 2016; 31(11):1360–1366. doi:10.1007/s11606-016-3725-z
  6. Guo F, Cofie LE, Berenson AB. Cervical cancer incidence in young US females after human papillomavirus vaccine introduction. Am J Prev Med 2018; 55(2):197–204. doi:10.1016/j.amepre.2018.03.013
  7. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination—updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016; 65(49):1405–1408. doi:10.15585/mmwr.mm6549a5
  8. Centers for Disease Control and Prevention (CDC). Supplemental information and guidance for vaccination providers regarding use of 9-valent HPV vaccine Information for persons who started an HPV vaccination series with quadrivalent or bivalent HPV vaccine. www.cdc.gov/hpv/downloads/9vhpv-guidance.pdf. Accessed February 14, 2019.
  9. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA 2013; 309(17):1793–1802. doi:10.1001/jama.2013.1625
  10. Markowitz LE, Dunne EF, Saraiya M, et al; Centers for Disease Control and Prevention (CDC). Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2014; 63(RR-05):1–30. pmid:25167164
  11. Thompson EL, Rosen BL, Vamos CA, Kadono M, Daley EM. Human papillomavirus vaccination: what are the reasons for nonvaccination among US adolescents? J Adolesc Health 2017; 61(3):288–293. doi:10.1016/j.jadohealth.2017.05.015
  12. Reagan-Steiner S, Yankey D, Jeyarajah J, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep 2016; 65(33):850–858. doi:10.15585/mmwr.mm6533a4
  13. Gilkey MB, Calo WA, Moss JL, Shah PD, Marciniak MW, Brewer NT. Provider communication and HPV vaccination: The impact of recommendation quality. Vaccine 2016; 34(9):1187–1192. doi:10.1016/j.vaccine.2016.01.023
  14. Brewer NT, Hall ME, Malo TL, Gilkey MB, Quinn B, Lathren C. Announcements versus conversations to improve HPV vaccination coverage: a randomized trial. Pediatrics 2017; 139(1):e20161764. doi:10.1542/peds.2016-1764
  15. American Cancer Society. HPV vaccine facts. www.cancer.org/cancer/cancer-causes/infectious-agents/hpv/hpv-vaccine-facts-and-fears.html. Accessed February 14, 2019.
  16. National Cancer Institute; Chasan R, Manrow R. Cervical cancer. https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76. Accessed February 14, 2019.
  17. The American College of Obstetricians and Gynecologists (ACOG). Frequently asked questions. Cervical cancer screening. www.acog.org/Patients/FAQs/Cervical-Cancer-Screening. Accessed February 14, 2019.
  18. Saslow D, Solomon D, Lawson HW, et al; American Cancer Society; American Society for Colposcopy and Cervical Pathology; American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol 2012; 137(4):516–542. doi:10.1309/AJCPTGD94EVRSJCG
  19. US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for cervical cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 320(7):674–686. doi:10.1001/jama.2018.10897
  20. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015; 136(2):189–197. doi:10.1016/j.ygyno.2014.11.076
  21. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstet Gynecol 2015; 125(2):330–337. doi:10.1097/AOG.0000000000000669
  22. Massad LS, Einstein MH, Huh WK, et al; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013; 121(4):829–846. doi:10.1097/AOG.0b013e3182883a34
  23. Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: cervical cancer screening and prevention. Obstet Gynecol 2016; 128(4):e111–e130. doi:10.1097/AOG.0000000000001708
  24. ASCCP. Mobile app. http://www.asccp.org/store-detail2/asccp-mobile-app. Accessed February 14, 2019.
  25. USPSTF. Draft recommendation: cervical cancer: screening. www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/cervical-cancer-screening2. Accessed February 14, 2019.
  26. Masur H, Brooks JT, Benson CA, Holmes KK, Pau AK, Kaplan JE; National Institutes of Health; Centers for Disease Control and Prevention; HIV Medicine Association of the Infectious Diseases Society of America. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58(9):1308–1311. doi:10.1093/cid/ciu094
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Human papillomavirus in 2019: An update on cervical cancer prevention and screening guidelines
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KEY POINTS

  • Immunization against HPV can prevent up to 70% of HPV-related cervical cancer cases.
  • Gardasil 9 is the only HPV vaccine currently available in the United States and is now approved for use in males and females between the ages of 9 and 45.
  • In girls and boys younger than 15, a 2-dose schedule is recommended; patients ages 15 through 45 require 3 doses.
  • Vaccine acceptance rates are highest when primary care providers announce that the vaccine is due rather than invite open-ended discussions.
  • Regular cervical cancer screening is an important preventive tool and should be performed using the Papanicolaou (Pap) test, the high-risk HPV-only test, or the Pap-HPV cotest.
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Cancer screening: A modest proposal for prevention

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Cancer screening: A modest proposal for prevention

I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed is at a year old, a most delicious, nourishing, and wholesome food, whether stewed, roasted, baked, or boiled, and I make no doubt that it will equally serve in a fricassee, or ragout.

—Jonathan Swift, A Modest Proposal1

Large-scale cancer screening programs have the unintended consequences of false-positive results and overdiagnosis, leading to anxiety and overtreatment. The magnitude of these harms continues to be clarified after decades of screening.

Recognizing the trade-off between benefits and harms, the US Preventive Services Task Force (USPSTF) has changed several of its recommendations in recent years. Breast cancer screening recommendations have gone from yearly mammograms starting at age 40 to biennial mammograms starting at age 50 for women at average risk.2 Prostate cancer screening is no longer recommended for men age 70 and older, and even for men between 55 and 69, screening is now an individual decision.3

Newer screening programs are targeting high-risk groups rather than the general population, with the aim of increasing the likelihood of benefits and limiting the harms. For example, lung cancer screening is recommended only for current smokers or smokers who have quit within the past 15 years, are between 55 and 80, and have at least a 30 pack-year smoking history.4

The movement toward less-frequent screening and screening in a narrower population has evoked strong reactions from advocates of cancer screening. One professor of radiology writes, “It borders on unethical to suggest that the benefit of having your life saved by screening and living another 40 years can be balanced against the ‘harm’ of being recalled for additional mammographic views for what proves to not be a cancer.”5 Another notes, “It does not make any sense to throw away the lives saved by screening to avoid over-treating a small number of cancers.”6 Both of these authors defend the position that the goal of screening is to minimize cause-specific mortality, irrespective of overdiagnosis, overtreatment, or false-positive results. In other words, harm should have little to no weight in screening recommendations.

Although the debate on cancer screening is moving toward a more balanced discussion of benefits and harms, many patients are still subjected to screening that is more aggressive than the USPSTF recommends, which may be due to an underlying belief that no harm is greater than the benefit of saving a life.

IS MORE-AGGRESSIVE SCREENING THE ANSWER?

Table 1. Benefit of cancer screening
Worst of all, when we examine the numbers, cancer screening is not very effective (Table 1).2–4,7,8 Even using optimistic estimates of its benefit, it is at best a half measure. Although screening, by detecting more cases of cancer at an early, potentially treatable stage, does save some lives from that cancer, many more people continue to die of cancer in spite of screening.

One may wonder if more-aggressive screening could prevent deaths that occur despite standard screening. For example, more-frequent screening or use of additional screening methods such as ultrasonography or magnetic resonance imaging has been suggested for patients at high risk of breast cancer.

A MODEST PROPOSAL

If one holds the view that benefits alone should be considered when writing recommendations about screening, the logical conclusion extends beyond screening. We would therefore like to propose a different approach to reducing cancer deaths in the general population:

Why not just remove everybody’s breasts, prostate gland, and colon before cancer arises?

 

 

TO CUT IS TO PREVENT

Currently, we offer prophylactic surgery to patients at high risk of cancer. For example, women with BRCA1/BRCA2 mutations are offered prophylactic mastectomy as one of several options for reducing risk of breast cancer. In 2013, the first case of prophylactic prostatectomy was performed in a man who had a BRCA1/BRCA2 mutation. Total colectomy is considered in men and women who have hereditary nonpolyposis colon cancer, instead of segmental resection, to prevent future cancer.

If prophylactic surgery were extended to the general population, it would greatly reduce the number of cancer deaths. Assuming that removing an organ almost always precludes development of cancer, we may predict that prophylactic mastectomy, prostatectomy, or colectomy would save the lives of most of the patients who are still dying of cancer of these organs. The effectiveness rates would approach, but not reach 100%; such is the case with prophylactic mastectomy.

Consider prostate-specific antigen (PSA) screening. Even using the favorable estimate of the impact of PSA screening, arising from the European Randomised Study of Screening for Prostate Cancer trial, 27 men have to be diagnosed, most undergoing local therapy (the trial was conducted before active surveillance became routine), to avert 1 death from prostate cancer over 13 years.9

Contrast this “number needed to diagnose” with the number needed to treat for a strategy of routine prostate removal at age 45 or 50. Given that the lifetime risk of death from prostate cancer approaches 3%, and few cases arise before this age, a prophylactic surgical strategy would avert 1 death per 33 operations. If proponents of screening are willing to accept a number needed to diagnose of 27 over a 13-year interval, they may be willing to consider a number needed to treat of 33 over a lifetime.

There may be harms such as perioperative and postoperative complications. Mastectomy could lead to emotional stress from altered body image. Prostatectomy can have long-term complications such as urinary incontinence and sexual dysfunction. Nevertheless, prophylactic organ removal would save far more lives than current screening practices. It also could decrease mental burden, as patients could rest assured that they will never develop cancer, whereas screening often involves ambiguous test results, follow-up tests, and interventions, increasing patient anxiety.

FINDING THE BALANCE BETWEEN BENEFITS AND HARMS

In truth, we do not really advocate universal mastectomy, prostatectomy, and colectomy to prevent cancer, no more than Swift1 really wanted to eat the children of Ireland to alleviate poverty and famine in that country.  Rather, we use it as an extreme proposal to highlight the scope and depth of harms that inevitably arise from screening.

If proponents of aggressive screening believe that the goal is to reduce cause-specific mortality as much as possible, giving little weight or consideration to overdiagnosis and overtreatment, then they ought to embrace universal prophylactic surgery as well. Recognition of this logical consequence reminds us that we must make screening recommendations that balance benefits and harms.

Considering an extreme perspective can help in recognizing our bias toward saving lives from cancer and discounting the harms. Aggravating this bias, it is impossible to know whether an individual patient has avoided fatal cancer or undergone unnecessary treatment. Moreover, changing practice is more difficult if it involves rolling back interventions that were once the standard.

Balancing benefits and harms is especially difficult when trying to compare the benefit of preventing a single cancer death against a harm that is less serious but more common. Medicine has always involved difficult trade-offs, as seen in cost-benefit analysis of new treatments or balancing quality of life with quantity of life in a single patient. In addition, each individual may place different values on benefits of screening and avoiding possible harms.

There is an undeniable trade-off with screening, and we must make a conscious decision on where to draw the line when harms outweigh the benefits. We must proceed with caution when subjecting large numbers of men and women to the possibility of psychological burden and decreased quality of life.

Given the growing appreciation of the harms of screening, it is likely that future guidance will continue to move toward less- frequent screening or focusing resources on high-risk populations, where the absolute magnitude of benefit is greater. Cancer screening is also likely to become an individual decision based on personal values and informed decisions.

References
  1. Swift J. A Modest Proposal for Preventing the Children of Poor People in Ireland, from Being a Burden on Their Parents or Country, and for Making Them Beneficial to the Publick. Dublin: S. Harding, 1729.
  2. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK343819. Accessed February 13, 2019.
  3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319(18):1901–1913. doi:10.1001/jama.2018.3710
  4. Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK154610. Accessed February 13, 2019.
  5. Kopans DB. A review of: “Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years.” www.sbi-online.org/Portals/0/downloads/documents/pdfs/A%20review%20of%20Tipping%20the%20Balance%20of%20Benefits%20and%20Harms%20to%20Favor%20Screening%20Mammography%20Starting%20at%20Age%2040%20Years%20-%20Kopans.pdf. Accessed February 13, 2019.
  6. Yaffe M, Gordon, P. Routine mammograms do save lives: U of T expert.  U of T News. www.utoronto.ca/news/routine-mammograms-do-save-lives-u-t-expert. Accessed February 13, 2019.
  7. Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
  8. Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828  
  9. Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384(9959):2027–2035. doi:10.1016/S0140-6736(14)60525-0
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Myung S. Kim, MD
Department of Internal Medicine, PeaceHealth Medical Group, Eugene, OR

Go Nishikawa, MD
Department of Medicine, Oregon Health and Science University, Portland, OR

Vinay Prasad, MD, MPH
Division of Hematology Oncology, Knight Cancer Institute; Department of Public Health and Preventive Medicine; Senior Scholar in the Center for Ethics in Health Care, Oregon Health and Science University, Portland, OR

Address: Vinay Prasad, MD, MPH, Assistant Professor of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; [email protected]

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Department of Internal Medicine, PeaceHealth Medical Group, Eugene, OR

Go Nishikawa, MD
Department of Medicine, Oregon Health and Science University, Portland, OR

Vinay Prasad, MD, MPH
Division of Hematology Oncology, Knight Cancer Institute; Department of Public Health and Preventive Medicine; Senior Scholar in the Center for Ethics in Health Care, Oregon Health and Science University, Portland, OR

Address: Vinay Prasad, MD, MPH, Assistant Professor of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; [email protected]

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Myung S. Kim, MD
Department of Internal Medicine, PeaceHealth Medical Group, Eugene, OR

Go Nishikawa, MD
Department of Medicine, Oregon Health and Science University, Portland, OR

Vinay Prasad, MD, MPH
Division of Hematology Oncology, Knight Cancer Institute; Department of Public Health and Preventive Medicine; Senior Scholar in the Center for Ethics in Health Care, Oregon Health and Science University, Portland, OR

Address: Vinay Prasad, MD, MPH, Assistant Professor of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; [email protected]

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I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed is at a year old, a most delicious, nourishing, and wholesome food, whether stewed, roasted, baked, or boiled, and I make no doubt that it will equally serve in a fricassee, or ragout.

—Jonathan Swift, A Modest Proposal1

Large-scale cancer screening programs have the unintended consequences of false-positive results and overdiagnosis, leading to anxiety and overtreatment. The magnitude of these harms continues to be clarified after decades of screening.

Recognizing the trade-off between benefits and harms, the US Preventive Services Task Force (USPSTF) has changed several of its recommendations in recent years. Breast cancer screening recommendations have gone from yearly mammograms starting at age 40 to biennial mammograms starting at age 50 for women at average risk.2 Prostate cancer screening is no longer recommended for men age 70 and older, and even for men between 55 and 69, screening is now an individual decision.3

Newer screening programs are targeting high-risk groups rather than the general population, with the aim of increasing the likelihood of benefits and limiting the harms. For example, lung cancer screening is recommended only for current smokers or smokers who have quit within the past 15 years, are between 55 and 80, and have at least a 30 pack-year smoking history.4

The movement toward less-frequent screening and screening in a narrower population has evoked strong reactions from advocates of cancer screening. One professor of radiology writes, “It borders on unethical to suggest that the benefit of having your life saved by screening and living another 40 years can be balanced against the ‘harm’ of being recalled for additional mammographic views for what proves to not be a cancer.”5 Another notes, “It does not make any sense to throw away the lives saved by screening to avoid over-treating a small number of cancers.”6 Both of these authors defend the position that the goal of screening is to minimize cause-specific mortality, irrespective of overdiagnosis, overtreatment, or false-positive results. In other words, harm should have little to no weight in screening recommendations.

Although the debate on cancer screening is moving toward a more balanced discussion of benefits and harms, many patients are still subjected to screening that is more aggressive than the USPSTF recommends, which may be due to an underlying belief that no harm is greater than the benefit of saving a life.

IS MORE-AGGRESSIVE SCREENING THE ANSWER?

Table 1. Benefit of cancer screening
Worst of all, when we examine the numbers, cancer screening is not very effective (Table 1).2–4,7,8 Even using optimistic estimates of its benefit, it is at best a half measure. Although screening, by detecting more cases of cancer at an early, potentially treatable stage, does save some lives from that cancer, many more people continue to die of cancer in spite of screening.

One may wonder if more-aggressive screening could prevent deaths that occur despite standard screening. For example, more-frequent screening or use of additional screening methods such as ultrasonography or magnetic resonance imaging has been suggested for patients at high risk of breast cancer.

A MODEST PROPOSAL

If one holds the view that benefits alone should be considered when writing recommendations about screening, the logical conclusion extends beyond screening. We would therefore like to propose a different approach to reducing cancer deaths in the general population:

Why not just remove everybody’s breasts, prostate gland, and colon before cancer arises?

 

 

TO CUT IS TO PREVENT

Currently, we offer prophylactic surgery to patients at high risk of cancer. For example, women with BRCA1/BRCA2 mutations are offered prophylactic mastectomy as one of several options for reducing risk of breast cancer. In 2013, the first case of prophylactic prostatectomy was performed in a man who had a BRCA1/BRCA2 mutation. Total colectomy is considered in men and women who have hereditary nonpolyposis colon cancer, instead of segmental resection, to prevent future cancer.

If prophylactic surgery were extended to the general population, it would greatly reduce the number of cancer deaths. Assuming that removing an organ almost always precludes development of cancer, we may predict that prophylactic mastectomy, prostatectomy, or colectomy would save the lives of most of the patients who are still dying of cancer of these organs. The effectiveness rates would approach, but not reach 100%; such is the case with prophylactic mastectomy.

Consider prostate-specific antigen (PSA) screening. Even using the favorable estimate of the impact of PSA screening, arising from the European Randomised Study of Screening for Prostate Cancer trial, 27 men have to be diagnosed, most undergoing local therapy (the trial was conducted before active surveillance became routine), to avert 1 death from prostate cancer over 13 years.9

Contrast this “number needed to diagnose” with the number needed to treat for a strategy of routine prostate removal at age 45 or 50. Given that the lifetime risk of death from prostate cancer approaches 3%, and few cases arise before this age, a prophylactic surgical strategy would avert 1 death per 33 operations. If proponents of screening are willing to accept a number needed to diagnose of 27 over a 13-year interval, they may be willing to consider a number needed to treat of 33 over a lifetime.

There may be harms such as perioperative and postoperative complications. Mastectomy could lead to emotional stress from altered body image. Prostatectomy can have long-term complications such as urinary incontinence and sexual dysfunction. Nevertheless, prophylactic organ removal would save far more lives than current screening practices. It also could decrease mental burden, as patients could rest assured that they will never develop cancer, whereas screening often involves ambiguous test results, follow-up tests, and interventions, increasing patient anxiety.

FINDING THE BALANCE BETWEEN BENEFITS AND HARMS

In truth, we do not really advocate universal mastectomy, prostatectomy, and colectomy to prevent cancer, no more than Swift1 really wanted to eat the children of Ireland to alleviate poverty and famine in that country.  Rather, we use it as an extreme proposal to highlight the scope and depth of harms that inevitably arise from screening.

If proponents of aggressive screening believe that the goal is to reduce cause-specific mortality as much as possible, giving little weight or consideration to overdiagnosis and overtreatment, then they ought to embrace universal prophylactic surgery as well. Recognition of this logical consequence reminds us that we must make screening recommendations that balance benefits and harms.

Considering an extreme perspective can help in recognizing our bias toward saving lives from cancer and discounting the harms. Aggravating this bias, it is impossible to know whether an individual patient has avoided fatal cancer or undergone unnecessary treatment. Moreover, changing practice is more difficult if it involves rolling back interventions that were once the standard.

Balancing benefits and harms is especially difficult when trying to compare the benefit of preventing a single cancer death against a harm that is less serious but more common. Medicine has always involved difficult trade-offs, as seen in cost-benefit analysis of new treatments or balancing quality of life with quantity of life in a single patient. In addition, each individual may place different values on benefits of screening and avoiding possible harms.

There is an undeniable trade-off with screening, and we must make a conscious decision on where to draw the line when harms outweigh the benefits. We must proceed with caution when subjecting large numbers of men and women to the possibility of psychological burden and decreased quality of life.

Given the growing appreciation of the harms of screening, it is likely that future guidance will continue to move toward less- frequent screening or focusing resources on high-risk populations, where the absolute magnitude of benefit is greater. Cancer screening is also likely to become an individual decision based on personal values and informed decisions.

I have been assured by a very knowing American of my acquaintance in London, that a young healthy child well nursed is at a year old, a most delicious, nourishing, and wholesome food, whether stewed, roasted, baked, or boiled, and I make no doubt that it will equally serve in a fricassee, or ragout.

—Jonathan Swift, A Modest Proposal1

Large-scale cancer screening programs have the unintended consequences of false-positive results and overdiagnosis, leading to anxiety and overtreatment. The magnitude of these harms continues to be clarified after decades of screening.

Recognizing the trade-off between benefits and harms, the US Preventive Services Task Force (USPSTF) has changed several of its recommendations in recent years. Breast cancer screening recommendations have gone from yearly mammograms starting at age 40 to biennial mammograms starting at age 50 for women at average risk.2 Prostate cancer screening is no longer recommended for men age 70 and older, and even for men between 55 and 69, screening is now an individual decision.3

Newer screening programs are targeting high-risk groups rather than the general population, with the aim of increasing the likelihood of benefits and limiting the harms. For example, lung cancer screening is recommended only for current smokers or smokers who have quit within the past 15 years, are between 55 and 80, and have at least a 30 pack-year smoking history.4

The movement toward less-frequent screening and screening in a narrower population has evoked strong reactions from advocates of cancer screening. One professor of radiology writes, “It borders on unethical to suggest that the benefit of having your life saved by screening and living another 40 years can be balanced against the ‘harm’ of being recalled for additional mammographic views for what proves to not be a cancer.”5 Another notes, “It does not make any sense to throw away the lives saved by screening to avoid over-treating a small number of cancers.”6 Both of these authors defend the position that the goal of screening is to minimize cause-specific mortality, irrespective of overdiagnosis, overtreatment, or false-positive results. In other words, harm should have little to no weight in screening recommendations.

Although the debate on cancer screening is moving toward a more balanced discussion of benefits and harms, many patients are still subjected to screening that is more aggressive than the USPSTF recommends, which may be due to an underlying belief that no harm is greater than the benefit of saving a life.

IS MORE-AGGRESSIVE SCREENING THE ANSWER?

Table 1. Benefit of cancer screening
Worst of all, when we examine the numbers, cancer screening is not very effective (Table 1).2–4,7,8 Even using optimistic estimates of its benefit, it is at best a half measure. Although screening, by detecting more cases of cancer at an early, potentially treatable stage, does save some lives from that cancer, many more people continue to die of cancer in spite of screening.

One may wonder if more-aggressive screening could prevent deaths that occur despite standard screening. For example, more-frequent screening or use of additional screening methods such as ultrasonography or magnetic resonance imaging has been suggested for patients at high risk of breast cancer.

A MODEST PROPOSAL

If one holds the view that benefits alone should be considered when writing recommendations about screening, the logical conclusion extends beyond screening. We would therefore like to propose a different approach to reducing cancer deaths in the general population:

Why not just remove everybody’s breasts, prostate gland, and colon before cancer arises?

 

 

TO CUT IS TO PREVENT

Currently, we offer prophylactic surgery to patients at high risk of cancer. For example, women with BRCA1/BRCA2 mutations are offered prophylactic mastectomy as one of several options for reducing risk of breast cancer. In 2013, the first case of prophylactic prostatectomy was performed in a man who had a BRCA1/BRCA2 mutation. Total colectomy is considered in men and women who have hereditary nonpolyposis colon cancer, instead of segmental resection, to prevent future cancer.

If prophylactic surgery were extended to the general population, it would greatly reduce the number of cancer deaths. Assuming that removing an organ almost always precludes development of cancer, we may predict that prophylactic mastectomy, prostatectomy, or colectomy would save the lives of most of the patients who are still dying of cancer of these organs. The effectiveness rates would approach, but not reach 100%; such is the case with prophylactic mastectomy.

Consider prostate-specific antigen (PSA) screening. Even using the favorable estimate of the impact of PSA screening, arising from the European Randomised Study of Screening for Prostate Cancer trial, 27 men have to be diagnosed, most undergoing local therapy (the trial was conducted before active surveillance became routine), to avert 1 death from prostate cancer over 13 years.9

Contrast this “number needed to diagnose” with the number needed to treat for a strategy of routine prostate removal at age 45 or 50. Given that the lifetime risk of death from prostate cancer approaches 3%, and few cases arise before this age, a prophylactic surgical strategy would avert 1 death per 33 operations. If proponents of screening are willing to accept a number needed to diagnose of 27 over a 13-year interval, they may be willing to consider a number needed to treat of 33 over a lifetime.

There may be harms such as perioperative and postoperative complications. Mastectomy could lead to emotional stress from altered body image. Prostatectomy can have long-term complications such as urinary incontinence and sexual dysfunction. Nevertheless, prophylactic organ removal would save far more lives than current screening practices. It also could decrease mental burden, as patients could rest assured that they will never develop cancer, whereas screening often involves ambiguous test results, follow-up tests, and interventions, increasing patient anxiety.

FINDING THE BALANCE BETWEEN BENEFITS AND HARMS

In truth, we do not really advocate universal mastectomy, prostatectomy, and colectomy to prevent cancer, no more than Swift1 really wanted to eat the children of Ireland to alleviate poverty and famine in that country.  Rather, we use it as an extreme proposal to highlight the scope and depth of harms that inevitably arise from screening.

If proponents of aggressive screening believe that the goal is to reduce cause-specific mortality as much as possible, giving little weight or consideration to overdiagnosis and overtreatment, then they ought to embrace universal prophylactic surgery as well. Recognition of this logical consequence reminds us that we must make screening recommendations that balance benefits and harms.

Considering an extreme perspective can help in recognizing our bias toward saving lives from cancer and discounting the harms. Aggravating this bias, it is impossible to know whether an individual patient has avoided fatal cancer or undergone unnecessary treatment. Moreover, changing practice is more difficult if it involves rolling back interventions that were once the standard.

Balancing benefits and harms is especially difficult when trying to compare the benefit of preventing a single cancer death against a harm that is less serious but more common. Medicine has always involved difficult trade-offs, as seen in cost-benefit analysis of new treatments or balancing quality of life with quantity of life in a single patient. In addition, each individual may place different values on benefits of screening and avoiding possible harms.

There is an undeniable trade-off with screening, and we must make a conscious decision on where to draw the line when harms outweigh the benefits. We must proceed with caution when subjecting large numbers of men and women to the possibility of psychological burden and decreased quality of life.

Given the growing appreciation of the harms of screening, it is likely that future guidance will continue to move toward less- frequent screening or focusing resources on high-risk populations, where the absolute magnitude of benefit is greater. Cancer screening is also likely to become an individual decision based on personal values and informed decisions.

References
  1. Swift J. A Modest Proposal for Preventing the Children of Poor People in Ireland, from Being a Burden on Their Parents or Country, and for Making Them Beneficial to the Publick. Dublin: S. Harding, 1729.
  2. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK343819. Accessed February 13, 2019.
  3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319(18):1901–1913. doi:10.1001/jama.2018.3710
  4. Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK154610. Accessed February 13, 2019.
  5. Kopans DB. A review of: “Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years.” www.sbi-online.org/Portals/0/downloads/documents/pdfs/A%20review%20of%20Tipping%20the%20Balance%20of%20Benefits%20and%20Harms%20to%20Favor%20Screening%20Mammography%20Starting%20at%20Age%2040%20Years%20-%20Kopans.pdf. Accessed February 13, 2019.
  6. Yaffe M, Gordon, P. Routine mammograms do save lives: U of T expert.  U of T News. www.utoronto.ca/news/routine-mammograms-do-save-lives-u-t-expert. Accessed February 13, 2019.
  7. Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
  8. Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828  
  9. Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384(9959):2027–2035. doi:10.1016/S0140-6736(14)60525-0
References
  1. Swift J. A Modest Proposal for Preventing the Children of Poor People in Ireland, from Being a Burden on Their Parents or Country, and for Making Them Beneficial to the Publick. Dublin: S. Harding, 1729.
  2. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK343819. Accessed February 13, 2019.
  3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018; 319(18):1901–1913. doi:10.1001/jama.2018.3710
  4. Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force Recommendation. www.ncbi.nlm.nih.gov/books/NBK154610. Accessed February 13, 2019.
  5. Kopans DB. A review of: “Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years.” www.sbi-online.org/Portals/0/downloads/documents/pdfs/A%20review%20of%20Tipping%20the%20Balance%20of%20Benefits%20and%20Harms%20to%20Favor%20Screening%20Mammography%20Starting%20at%20Age%2040%20Years%20-%20Kopans.pdf. Accessed February 13, 2019.
  6. Yaffe M, Gordon, P. Routine mammograms do save lives: U of T expert.  U of T News. www.utoronto.ca/news/routine-mammograms-do-save-lives-u-t-expert. Accessed February 13, 2019.
  7. Lin JS, Piper MA, Perdue LA, et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2016; 315(23):2576–2594. doi:10.1001/jama.2016.3332
  8. Knudsen AB, Zauber AG, Rutter CM, et al. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA 2016; 315(23):2595–2609. doi:10.1001/jama.2016.6828  
  9. Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384(9959):2027–2035. doi:10.1016/S0140-6736(14)60525-0
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Cancer screening: A modest proposal for prevention
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cancer screening, testing, benefit, harm, US Preventive Services Task Force, USPSTF, Jonathan Swift, modest proposal, breast cancer, mammography, colon cancer, sigmoidoscopy, fecal occult blood test, guaiac, colonoscopy, prostate cancer, prostate-specific antigen, lung cancer, computed tomography, CT, trade-off, informed decision, Myung Kim, Go Nishikawa, Vinay Prasad
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cancer screening, testing, benefit, harm, US Preventive Services Task Force, USPSTF, Jonathan Swift, modest proposal, breast cancer, mammography, colon cancer, sigmoidoscopy, fecal occult blood test, guaiac, colonoscopy, prostate cancer, prostate-specific antigen, lung cancer, computed tomography, CT, trade-off, informed decision, Myung Kim, Go Nishikawa, Vinay Prasad
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Correction: Hypertension guidelines

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In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

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In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

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Masterclass: Marlene Freeman on treating bipolar disorder in women

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In this Masterclass episode of the MDedge Psychcast from the 2018 AACP Encore meeting in Las Vegas, Dr. Marlene Freeman discusses the latest studies on the risks of treating – and not treating – women with bipolar disorder during pregnancy. Dr. Freeman, associate professor of psychiatry at Harvard Medical School, also shares preliminary data on the impact of exposure to atypical antipsychotics from the National Pregnancy Registry for Psychiatric Medications at Massachusetts General Hospital, where she also serves as associate director of Women’s Mental Health.
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In this Masterclass episode of the MDedge Psychcast from the 2018 AACP Encore meeting in Las Vegas, Dr. Marlene Freeman discusses the latest studies on the risks of treating – and not treating – women with bipolar disorder during pregnancy. Dr. Freeman, associate professor of psychiatry at Harvard Medical School, also shares preliminary data on the impact of exposure to atypical antipsychotics from the National Pregnancy Registry for Psychiatric Medications at Massachusetts General Hospital, where she also serves as associate director of Women’s Mental Health.
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In this Masterclass episode of the MDedge Psychcast from the 2018 AACP Encore meeting in Las Vegas, Dr. Marlene Freeman discusses the latest studies on the risks of treating – and not treating – women with bipolar disorder during pregnancy. Dr. Freeman, associate professor of psychiatry at Harvard Medical School, also shares preliminary data on the impact of exposure to atypical antipsychotics from the National Pregnancy Registry for Psychiatric Medications at Massachusetts General Hospital, where she also serves as associate director of Women’s Mental Health.
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Insulin-treated diabetes in pregnancy carries preterm risk

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Women with insulin-treated diabetes are at significantly greater risk of preterm birth and of delivering babies who are large for gestational age (LGA), regardless of prepregnancy body weight, new findings suggest.

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Researchers examined the role of maternal diabetes and weight on pregnancy outcomes in the population-based cohort study. The study comprised 649,043 live births in Finland between Jan. 1, 2004, and Dec. 31, 2014, including 4,000 in women with insulin-treated diabetes, 3,740 in women with type 2 diabetes, and 98,568 women with gestational diabetes.

Prepregnancy body mass index was normal for nearly 60% of mothers, while 4% were underweight, 21% were overweight, 8% were moderately obese, and 4% were severely obese.

Overall, the researchers found that women with insulin-treated diabetes had a 43-fold higher odds of having an LGA infant, compared with the reference group of women of normal BMI without diabetes (adjusted odds ratio [aOR], 43.80; 95% confidence interval, 40.88-46.93). And there was an 11-fold greater odds of having a preterm birth in this group (aOR, 11.17; 95% CI, 10.46-11.93).

The findings were published in JAMA Pediatrics.

“Smaller, but clearly statistically significant, increased LGA risks were found also for mothers with type 2 diabetes and gestational diabetes not treated with insulin, especially in combination with prepregnancy overweight or obesity that were stronger for type 2 diabetes than gestational diabetes,” wrote Linghua Kong, MSc, of the department of molecular medicine and surgery at Karolinska Institutet, and coauthors.

The aOR for LGA among women with type 2 diabetes was 9.57 (95% CI, 8.65-10.58), compared with the reference group. And for women with maternal gestational diabetes, the aOR for LGA was 3.80 (95% CI, 3.66-3.96).

 

 

Looking at the risk for preterm birth, the researchers found that the aOR among women with type 2 diabetes was 2.12 (95% CI, 1.90-2.36), while there was no association between gestational diabetes and preterm birth.

The researchers also reported that for women with gestational diabetes or no diabetes, the odds of preterm birth increased slightly as maternal prepregnancy BMI increased.

“Maternal glucose metabolism during pregnancy differs from that in the non-pregnant state; insulin resistance is increased, directing fat as the mother’s energy source to ensure adequate carbohydrate supply for the growing fetus,” the researchers wrote. “This increase in insulin resistance is mediated by a number of factors, such as increased levels of progesterone, estrogen, and human placental lactogen.”

The authors noted that their data did not include information on congenital anomalies, maternal complications such as preeclampsia, and grade of diabetes control during pregnancy. In addition, the data on maternal BMI was derived from a single time point.

“These findings may have implications for counseling and managing pregnancies to prevent adverse birth outcomes,” they wrote.

The study and some authors were supported by the THL National Institute for Health and Welfare, the Swedish Research Council, Stockholm County Council, the China Scholarship Council, and the Swedish Brain Foundation.

SOURCE: Kong L et al. JAMA Pediatr. 2019 Feb 25. doi: 10.1001/jamapediatrics.2018.5541.

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Women with insulin-treated diabetes are at significantly greater risk of preterm birth and of delivering babies who are large for gestational age (LGA), regardless of prepregnancy body weight, new findings suggest.

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Researchers examined the role of maternal diabetes and weight on pregnancy outcomes in the population-based cohort study. The study comprised 649,043 live births in Finland between Jan. 1, 2004, and Dec. 31, 2014, including 4,000 in women with insulin-treated diabetes, 3,740 in women with type 2 diabetes, and 98,568 women with gestational diabetes.

Prepregnancy body mass index was normal for nearly 60% of mothers, while 4% were underweight, 21% were overweight, 8% were moderately obese, and 4% were severely obese.

Overall, the researchers found that women with insulin-treated diabetes had a 43-fold higher odds of having an LGA infant, compared with the reference group of women of normal BMI without diabetes (adjusted odds ratio [aOR], 43.80; 95% confidence interval, 40.88-46.93). And there was an 11-fold greater odds of having a preterm birth in this group (aOR, 11.17; 95% CI, 10.46-11.93).

The findings were published in JAMA Pediatrics.

“Smaller, but clearly statistically significant, increased LGA risks were found also for mothers with type 2 diabetes and gestational diabetes not treated with insulin, especially in combination with prepregnancy overweight or obesity that were stronger for type 2 diabetes than gestational diabetes,” wrote Linghua Kong, MSc, of the department of molecular medicine and surgery at Karolinska Institutet, and coauthors.

The aOR for LGA among women with type 2 diabetes was 9.57 (95% CI, 8.65-10.58), compared with the reference group. And for women with maternal gestational diabetes, the aOR for LGA was 3.80 (95% CI, 3.66-3.96).

 

 

Looking at the risk for preterm birth, the researchers found that the aOR among women with type 2 diabetes was 2.12 (95% CI, 1.90-2.36), while there was no association between gestational diabetes and preterm birth.

The researchers also reported that for women with gestational diabetes or no diabetes, the odds of preterm birth increased slightly as maternal prepregnancy BMI increased.

“Maternal glucose metabolism during pregnancy differs from that in the non-pregnant state; insulin resistance is increased, directing fat as the mother’s energy source to ensure adequate carbohydrate supply for the growing fetus,” the researchers wrote. “This increase in insulin resistance is mediated by a number of factors, such as increased levels of progesterone, estrogen, and human placental lactogen.”

The authors noted that their data did not include information on congenital anomalies, maternal complications such as preeclampsia, and grade of diabetes control during pregnancy. In addition, the data on maternal BMI was derived from a single time point.

“These findings may have implications for counseling and managing pregnancies to prevent adverse birth outcomes,” they wrote.

The study and some authors were supported by the THL National Institute for Health and Welfare, the Swedish Research Council, Stockholm County Council, the China Scholarship Council, and the Swedish Brain Foundation.

SOURCE: Kong L et al. JAMA Pediatr. 2019 Feb 25. doi: 10.1001/jamapediatrics.2018.5541.

Women with insulin-treated diabetes are at significantly greater risk of preterm birth and of delivering babies who are large for gestational age (LGA), regardless of prepregnancy body weight, new findings suggest.

iStock

Researchers examined the role of maternal diabetes and weight on pregnancy outcomes in the population-based cohort study. The study comprised 649,043 live births in Finland between Jan. 1, 2004, and Dec. 31, 2014, including 4,000 in women with insulin-treated diabetes, 3,740 in women with type 2 diabetes, and 98,568 women with gestational diabetes.

Prepregnancy body mass index was normal for nearly 60% of mothers, while 4% were underweight, 21% were overweight, 8% were moderately obese, and 4% were severely obese.

Overall, the researchers found that women with insulin-treated diabetes had a 43-fold higher odds of having an LGA infant, compared with the reference group of women of normal BMI without diabetes (adjusted odds ratio [aOR], 43.80; 95% confidence interval, 40.88-46.93). And there was an 11-fold greater odds of having a preterm birth in this group (aOR, 11.17; 95% CI, 10.46-11.93).

The findings were published in JAMA Pediatrics.

“Smaller, but clearly statistically significant, increased LGA risks were found also for mothers with type 2 diabetes and gestational diabetes not treated with insulin, especially in combination with prepregnancy overweight or obesity that were stronger for type 2 diabetes than gestational diabetes,” wrote Linghua Kong, MSc, of the department of molecular medicine and surgery at Karolinska Institutet, and coauthors.

The aOR for LGA among women with type 2 diabetes was 9.57 (95% CI, 8.65-10.58), compared with the reference group. And for women with maternal gestational diabetes, the aOR for LGA was 3.80 (95% CI, 3.66-3.96).

 

 

Looking at the risk for preterm birth, the researchers found that the aOR among women with type 2 diabetes was 2.12 (95% CI, 1.90-2.36), while there was no association between gestational diabetes and preterm birth.

The researchers also reported that for women with gestational diabetes or no diabetes, the odds of preterm birth increased slightly as maternal prepregnancy BMI increased.

“Maternal glucose metabolism during pregnancy differs from that in the non-pregnant state; insulin resistance is increased, directing fat as the mother’s energy source to ensure adequate carbohydrate supply for the growing fetus,” the researchers wrote. “This increase in insulin resistance is mediated by a number of factors, such as increased levels of progesterone, estrogen, and human placental lactogen.”

The authors noted that their data did not include information on congenital anomalies, maternal complications such as preeclampsia, and grade of diabetes control during pregnancy. In addition, the data on maternal BMI was derived from a single time point.

“These findings may have implications for counseling and managing pregnancies to prevent adverse birth outcomes,” they wrote.

The study and some authors were supported by the THL National Institute for Health and Welfare, the Swedish Research Council, Stockholm County Council, the China Scholarship Council, and the Swedish Brain Foundation.

SOURCE: Kong L et al. JAMA Pediatr. 2019 Feb 25. doi: 10.1001/jamapediatrics.2018.5541.

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Key clinical point: Insulin-treated diabetes in pregnancy significantly increases the risk of large-for-gestational-age offspring and preterm birth.

Major finding: Pregnant women with insulin-treated diabetes have a 43-fold higher odds of having a child who is large for gestational age and 11-fold high risk for preterm birth.

Study details: A population-based cohort study of 649,043 live births in Finland between 2004 and 2014.

Disclosures: The study and some authors were supported by the THL National Institute for Health and Welfare, the Swedish Research Council, Stockholm County Council, the China Scholarship Council, and the Swedish Brain Foundation.

Source: Kong L et al. JAMA Pediatr. 2019 Feb 25. doi: 10.1001/jamapediatrics.2018.5541.

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