Vaccines

The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

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The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

[email protected]

The United States is now up to 314 confirmed cases of measles for 2019, with the count going up by 46 during the week ending March 21, according to the Centers for Disease Control and Prevention.

Despite those 46 new cases, the number of states with reported cases remains at 15, the CDC reported March 25.

For the fifth consecutive week the busiest outbreak was in Brooklyn, N.Y., which added 23 new cases. New York’s Rockland County, which is just north of New York City and has 46 confirmed cases for the year, is home to another of the six current outbreaks in the country, with the other four located in Washington (74 total cases for the state), Texas (14 cases), California (7 cases), and Illinois (6 cases). Other states with cases are Arizona, Colorado, Connecticut, Georgia, Kentucky, Missouri, New Hampshire, New Jersey, and Oregon, reported the CDC.

This year’s case total through less than 3 months is nearing the 372 that occurred in 2018, which was the second-worst year for measles in the last decade, but is still well off the 10-year high of 667 reported in 2014, the CDC said.

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Forty more cases and three more states were added to the measles count in the last week, bringing the U.S. total to 268 cases in 15 states so far in 2019, according to the Centers for Disease Control and Prevention.

Arizona, Michigan, and Missouri reported their first confirmed cases of the year, joining California (one outbreak), Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New Hampshire, New Jersey, New York (two outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC reported March 18.

Brooklyn, N.Y., has become the epicenter of measles activity since mid-February, and with 25 of the 40 new cases occurring there, the borough has now led the nation for four consecutive weeks. There have been 157 confirmed cases in Brooklyn and one in Queens since the outbreak began in October of 2018, the New York City Department of Health and Mental Hygiene reported.

Michigan’s first case of measles is travel related and involved an individual visiting from Israel following a stay in New York, the Michigan Department of Health and Human Services and Oakland County Health Division announced March 13.

In Arizona, the state department of health services and the Pima County Public Health Department announced that a 12-month-old infant from Pima County has been diagnosed with measles after traveling to Asia.

A single case of measles, contracted while the person was traveling out of state, has been reported in Jefferson County, Mo., and is being managed by the county health department, according to St. Louis Public Radio.

[email protected]

Forty more cases and three more states were added to the measles count in the last week, bringing the U.S. total to 268 cases in 15 states so far in 2019, according to the Centers for Disease Control and Prevention.

Arizona, Michigan, and Missouri reported their first confirmed cases of the year, joining California (one outbreak), Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New Hampshire, New Jersey, New York (two outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC reported March 18.

Brooklyn, N.Y., has become the epicenter of measles activity since mid-February, and with 25 of the 40 new cases occurring there, the borough has now led the nation for four consecutive weeks. There have been 157 confirmed cases in Brooklyn and one in Queens since the outbreak began in October of 2018, the New York City Department of Health and Mental Hygiene reported.

Michigan’s first case of measles is travel related and involved an individual visiting from Israel following a stay in New York, the Michigan Department of Health and Human Services and Oakland County Health Division announced March 13.

In Arizona, the state department of health services and the Pima County Public Health Department announced that a 12-month-old infant from Pima County has been diagnosed with measles after traveling to Asia.

A single case of measles, contracted while the person was traveling out of state, has been reported in Jefferson County, Mo., and is being managed by the county health department, according to St. Louis Public Radio.

[email protected]

Forty more cases and three more states were added to the measles count in the last week, bringing the U.S. total to 268 cases in 15 states so far in 2019, according to the Centers for Disease Control and Prevention.

Arizona, Michigan, and Missouri reported their first confirmed cases of the year, joining California (one outbreak), Colorado, Connecticut, Georgia, Illinois (one outbreak), Kentucky, New Hampshire, New Jersey, New York (two outbreaks), Oregon, Texas (one outbreak), and Washington (one outbreak), the CDC reported March 18.

Brooklyn, N.Y., has become the epicenter of measles activity since mid-February, and with 25 of the 40 new cases occurring there, the borough has now led the nation for four consecutive weeks. There have been 157 confirmed cases in Brooklyn and one in Queens since the outbreak began in October of 2018, the New York City Department of Health and Mental Hygiene reported.

Michigan’s first case of measles is travel related and involved an individual visiting from Israel following a stay in New York, the Michigan Department of Health and Human Services and Oakland County Health Division announced March 13.

In Arizona, the state department of health services and the Pima County Public Health Department announced that a 12-month-old infant from Pima County has been diagnosed with measles after traveling to Asia.

A single case of measles, contracted while the person was traveling out of state, has been reported in Jefferson County, Mo., and is being managed by the county health department, according to St. Louis Public Radio.

[email protected]

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

[email protected]

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

[email protected]

The number of new measles cases was down by more than half last week, but another state has been added to the list of those with reported cases in 2019, according to the Centers for Disease Control and Prevention.

There were 21 new measles cases reported to the CDC during the week ending March 7 – down from 47 the week before. The total for the year is 228 cases, which moves 2019 ahead of 2011 for third place over the last decade, the CDC reported March 11. Going back even further in time, the 206 measles cases reported through January and February is the highest 2-month total in a quarter of a century, the Washington Post said.

New Hampshire became the 12th and latest state to report a case of measles this year, joining California, Colorado, Connecticut, Georgia, Illinois, Kentucky, New Jersey, New York, Oregon, Texas, and Washington. California’s situation is now considered an outbreak (defined as three or more cases), but one of the three outbreaks in New York has been taken off the list, so total outbreaks for 2019 remain at six, the CDC said.

For the third consecutive week, New York City produced the most measles cases, with Brooklyn’s Williamsburg neighborhood recording 11 of the U.S. total of 21. The outbreak in King County, Wash., – totaling 70 cases this year – may be winding down as only one new case was reported last week, and no new cases are being investigated, the county’s public health service reported.

[email protected]

One of the most important commitments family physicians can undertake in protecting the health of their patients and communities is to ensure that their patients are fully vaccinated. This task is increasingly complicated as new vaccines are approved every year and recommendations change regarding new and established vaccines. To assist primary care providers, the Centers for Disease Control and Prevention (CDC) annually updates 2 immunization schedules—one for children and adolescents, and one for adults. These schedules are available on the CDC Web site (https://www.cdc.gov/vaccines/schedules/index.html).

These updates originate from the Advisory Committee on Immunization Practices (ACIP), which meets 3 times a year to consider and adopt changes to the schedules. During 2018, relatively few new recommendations were adopted. The September 2018 Practice Alert¹ in this journal covered the updated recommendations for influenza immunization, which included reinstating live attenuated influenza vaccine (LAIV) to the active list of influenza vaccines.

This current Practice Alert reviews 3 additional updates: 1) a new hepatitis B (HepB) vaccine; 2) updated recommendations for the use of hepatitis A (HepA) vaccine for post-exposure prevention and before travel; and 3) inclusion of the homeless among those who should be routinely vaccinated with HepA vaccine.

Hepatitis B: New 2-dose product

As of 2015, the annual incidence of new hepatitis B cases had declined by 88.5% since the first HepB vaccine was licensed in 1981 and recommendations for its routine use were issued in 1982.² The HepB vaccine products available in the United States are 2 single-antigen products, Engerix-B (GlaxoSmithKline) and Recombivax HB (Merck & Co.). Both can be used in all age groups, starting at birth, in a 3-dose series. HepB vaccine is also available in 2 combination products: Pediarix, containing HepB, diphtheria and tetanus toxoids, acellular pertussis, and inactivated poliovirus (GlaxoSmithKline), approved for use in children 6 weeks to 6 years old; and Twinrix (GlaxoSmithKline), which contains both HepB and HepA and is approved for use in adults 18 years and older.

The HepB vaccine is recommended for all children and unvaccinated adolescents as part of the routine vaccination schedule. It is also recommended for unvaccinated adults with specific risks (TABLE 1²). However, the rate of HepB vaccination in adults for whom it is recommended is suboptimal (FIGURE),³ and just a little more than half of adults who start a 3-dose series of HepB complete it.⁴A new vaccine against hepatitis B, HEPLISAV-B (Dynavax Technologies), was licensed by the US Food and Drug Administration in late 2017. ACIP now recommends it as an option along with other available HepB products. HEPLISAV-B is given in 2 doses separated by 1 month. It is hoped that this shortened 2-dose series will increase the number of adults who achieve full vaccination. In addition, it appears that HEPLISAV-B provides higher levels of protection in some high-risk groups—those with type 2 diabetes or chronic kidney disease.³ However, initial safety studies have shown a small absolute increase in cardiac events after vaccination with HEPLISAV-B. Post-marketing surveillance will be needed to show whether this is causal or coincidental.³

If a HepB series must be completed with different products, just be sure 3 doses are given—even if HEPLISAV-B is one of the agents.

As with other HepB products, use of HEPLISAV-B should follow the latest CDC directives on who to test serologically for prior immunity, and on post-vaccination testing to ensure protective antibody levels were achieved.² It is best to complete a HepB series with the same product, but, if necessary, a combination of products at different doses can be used to complete the HepB series. Any such combination should include 3 doses, even if one of the doses is HEPLISAV-B.

Hepatitis A: Vaccination assumes greater importance for more people

A Practice Alert in early 2018 described a series of outbreaks of hepatitis A around the country and the high rates of associated hospitalizations.⁵ These outbreaks have occurred primarily among the homeless and their contacts and those who use illicit drugs. This nationwide outbreak has now spread, resulting in more than 7500 cases since July 1, 2016.⁶ The progress of this epidemic can be viewed on the CDC Web site (https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm).⁷ At its October 2018 meeting, ACIP added homelessness to the list of those (previously unvaccinated) who should receive the HepA vaccine (TABLE 2).⁶

Continue to: Remember that the current recommendation...

Remember that the current recommendation is to vaccinate all children 12 to 23 months old with HepA, in 2 separate doses. Two single-antigen HepA products are available: Havrix (GSK) and Vaqta (Merck). For the 2-dose sequence, Havrix is given at 0 and 6 to 12 months; Vaqta at 0 and 6 to 18 months. Even a single dose will provide protection for up to 11 years. In addition to these vaccines, there is the combination HepA and HepB vaccine (Twinrix) mentioned earlier.

Previous recommendations for preventing hepatitis A after exposure, made in 2007, stated that HepA vaccine was preferred for healthy individuals ages 12 months through 40 years, while immune globulin (IG) was preferred for adults older than 40, infants before their first birthday, immunocompromised individuals, those with chronic liver disease, and those for whom HepA vaccine is contraindicated.⁸ The 2007 recommendations also advised vaccinating individuals traveling to countries with intermediate to high hepatitis A endemicity.

A single dose of HepA vaccine was recommended for all those 12 months or older, although older adults, immunocompromised individuals, and those with chronic liver disease or other chronic medical conditions planning to visit an endemic area in ≤ 2 weeks were supposed to receive the initial dose of vaccine and could also receive IG (0.02 mL/kg) if their provider advised it. Travelers who declined vaccination, those younger than 12 months, or those allergic to a vaccine component could receive a single dose of IG (0.02 mL/kg), which provides protection up to 3 months.

Consider prescribing daily pre-exposure prophylaxis for men and women at risk from sexual exposure to HIV or who inject illicit drugs.

Several factors influenced ACIP to reconsider both the pre- and post-exposure recommendations. Regarding IG, evidence of its decreased potency over time led the committee to increase the recommended dose (see below). IG also must be re-administered every 2 months, the supply of the product is questionable, and many health care facilities do not stock it. By comparison, HepA vaccine offers the advantages of easier administration, inducing active immunity, and providing longer protection. Another issue involved infants ages 6 to 11 months traveling to an area with endemic measles transmission and who must therefore receive the measles, mumps, and rubella (MMR) vaccine. MMR and IG should not be co-administered, and, for infants, the health risk from measles outweighs that from hepatitis A.

Updated recommendations. After considering all this information, ACIP made the following changes to its hepatitis A virus (HAV) prevention recommendations (in addition to adding homeless people to the list of HepA vaccine recipients)⁹:

• Administer HepA vaccine as post-exposure prophylaxis to all individuals 12 months and older.
• IG may be administered, in addition to HepA vaccine, to those older than 40 years, depending on the provider’s risk assessment (degree of exposure and medical conditions that might lead to severe complications from HAV infection). The recommended IG dose is now 0.1 mL/kg for post-exposure prevention; it is 0.1 to 0.2 mL/kg for pre-exposure prophylaxis for travelers, depending on the length of planned travel.
• Administer HepA vaccine alone to infants ages 6 to 11 months traveling outside the United States when protection against hepatitis A is recommended.

These recommendations have been published in the Morbidity and Mortality Weekly Report.⁹

One of the most important commitments family physicians can undertake in protecting the health of their patients and communities is to ensure that their patients are fully vaccinated. This task is increasingly complicated as new vaccines are approved every year and recommendations change regarding new and established vaccines. To assist primary care providers, the Centers for Disease Control and Prevention (CDC) annually updates 2 immunization schedules—one for children and adolescents, and one for adults. These schedules are available on the CDC Web site (https://www.cdc.gov/vaccines/schedules/index.html).

These updates originate from the Advisory Committee on Immunization Practices (ACIP), which meets 3 times a year to consider and adopt changes to the schedules. During 2018, relatively few new recommendations were adopted. The September 2018 Practice Alert¹ in this journal covered the updated recommendations for influenza immunization, which included reinstating live attenuated influenza vaccine (LAIV) to the active list of influenza vaccines.

This current Practice Alert reviews 3 additional updates: 1) a new hepatitis B (HepB) vaccine; 2) updated recommendations for the use of hepatitis A (HepA) vaccine for post-exposure prevention and before travel; and 3) inclusion of the homeless among those who should be routinely vaccinated with HepA vaccine.

Hepatitis B: New 2-dose product

As of 2015, the annual incidence of new hepatitis B cases had declined by 88.5% since the first HepB vaccine was licensed in 1981 and recommendations for its routine use were issued in 1982.² The HepB vaccine products available in the United States are 2 single-antigen products, Engerix-B (GlaxoSmithKline) and Recombivax HB (Merck & Co.). Both can be used in all age groups, starting at birth, in a 3-dose series. HepB vaccine is also available in 2 combination products: Pediarix, containing HepB, diphtheria and tetanus toxoids, acellular pertussis, and inactivated poliovirus (GlaxoSmithKline), approved for use in children 6 weeks to 6 years old; and Twinrix (GlaxoSmithKline), which contains both HepB and HepA and is approved for use in adults 18 years and older.

The HepB vaccine is recommended for all children and unvaccinated adolescents as part of the routine vaccination schedule. It is also recommended for unvaccinated adults with specific risks (TABLE 1²). However, the rate of HepB vaccination in adults for whom it is recommended is suboptimal (FIGURE),³ and just a little more than half of adults who start a 3-dose series of HepB complete it.⁴A new vaccine against hepatitis B, HEPLISAV-B (Dynavax Technologies), was licensed by the US Food and Drug Administration in late 2017. ACIP now recommends it as an option along with other available HepB products. HEPLISAV-B is given in 2 doses separated by 1 month. It is hoped that this shortened 2-dose series will increase the number of adults who achieve full vaccination. In addition, it appears that HEPLISAV-B provides higher levels of protection in some high-risk groups—those with type 2 diabetes or chronic kidney disease.³ However, initial safety studies have shown a small absolute increase in cardiac events after vaccination with HEPLISAV-B. Post-marketing surveillance will be needed to show whether this is causal or coincidental.³

If a HepB series must be completed with different products, just be sure 3 doses are given—even if HEPLISAV-B is one of the agents.

As with other HepB products, use of HEPLISAV-B should follow the latest CDC directives on who to test serologically for prior immunity, and on post-vaccination testing to ensure protective antibody levels were achieved.² It is best to complete a HepB series with the same product, but, if necessary, a combination of products at different doses can be used to complete the HepB series. Any such combination should include 3 doses, even if one of the doses is HEPLISAV-B.

Hepatitis A: Vaccination assumes greater importance for more people

A Practice Alert in early 2018 described a series of outbreaks of hepatitis A around the country and the high rates of associated hospitalizations.⁵ These outbreaks have occurred primarily among the homeless and their contacts and those who use illicit drugs. This nationwide outbreak has now spread, resulting in more than 7500 cases since July 1, 2016.⁶ The progress of this epidemic can be viewed on the CDC Web site (https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm).⁷ At its October 2018 meeting, ACIP added homelessness to the list of those (previously unvaccinated) who should receive the HepA vaccine (TABLE 2).⁶

Continue to: Remember that the current recommendation...

Remember that the current recommendation is to vaccinate all children 12 to 23 months old with HepA, in 2 separate doses. Two single-antigen HepA products are available: Havrix (GSK) and Vaqta (Merck). For the 2-dose sequence, Havrix is given at 0 and 6 to 12 months; Vaqta at 0 and 6 to 18 months. Even a single dose will provide protection for up to 11 years. In addition to these vaccines, there is the combination HepA and HepB vaccine (Twinrix) mentioned earlier.

Previous recommendations for preventing hepatitis A after exposure, made in 2007, stated that HepA vaccine was preferred for healthy individuals ages 12 months through 40 years, while immune globulin (IG) was preferred for adults older than 40, infants before their first birthday, immunocompromised individuals, those with chronic liver disease, and those for whom HepA vaccine is contraindicated.⁸ The 2007 recommendations also advised vaccinating individuals traveling to countries with intermediate to high hepatitis A endemicity.

A single dose of HepA vaccine was recommended for all those 12 months or older, although older adults, immunocompromised individuals, and those with chronic liver disease or other chronic medical conditions planning to visit an endemic area in ≤ 2 weeks were supposed to receive the initial dose of vaccine and could also receive IG (0.02 mL/kg) if their provider advised it. Travelers who declined vaccination, those younger than 12 months, or those allergic to a vaccine component could receive a single dose of IG (0.02 mL/kg), which provides protection up to 3 months.

Consider prescribing daily pre-exposure prophylaxis for men and women at risk from sexual exposure to HIV or who inject illicit drugs.

Several factors influenced ACIP to reconsider both the pre- and post-exposure recommendations. Regarding IG, evidence of its decreased potency over time led the committee to increase the recommended dose (see below). IG also must be re-administered every 2 months, the supply of the product is questionable, and many health care facilities do not stock it. By comparison, HepA vaccine offers the advantages of easier administration, inducing active immunity, and providing longer protection. Another issue involved infants ages 6 to 11 months traveling to an area with endemic measles transmission and who must therefore receive the measles, mumps, and rubella (MMR) vaccine. MMR and IG should not be co-administered, and, for infants, the health risk from measles outweighs that from hepatitis A.

Updated recommendations. After considering all this information, ACIP made the following changes to its hepatitis A virus (HAV) prevention recommendations (in addition to adding homeless people to the list of HepA vaccine recipients)⁹:

• Administer HepA vaccine as post-exposure prophylaxis to all individuals 12 months and older.
• IG may be administered, in addition to HepA vaccine, to those older than 40 years, depending on the provider’s risk assessment (degree of exposure and medical conditions that might lead to severe complications from HAV infection). The recommended IG dose is now 0.1 mL/kg for post-exposure prevention; it is 0.1 to 0.2 mL/kg for pre-exposure prophylaxis for travelers, depending on the length of planned travel.
• Administer HepA vaccine alone to infants ages 6 to 11 months traveling outside the United States when protection against hepatitis A is recommended.

These recommendations have been published in the Morbidity and Mortality Weekly Report.⁹

One of the most important commitments family physicians can undertake in protecting the health of their patients and communities is to ensure that their patients are fully vaccinated. This task is increasingly complicated as new vaccines are approved every year and recommendations change regarding new and established vaccines. To assist primary care providers, the Centers for Disease Control and Prevention (CDC) annually updates 2 immunization schedules—one for children and adolescents, and one for adults. These schedules are available on the CDC Web site (https://www.cdc.gov/vaccines/schedules/index.html).

These updates originate from the Advisory Committee on Immunization Practices (ACIP), which meets 3 times a year to consider and adopt changes to the schedules. During 2018, relatively few new recommendations were adopted. The September 2018 Practice Alert¹ in this journal covered the updated recommendations for influenza immunization, which included reinstating live attenuated influenza vaccine (LAIV) to the active list of influenza vaccines.

This current Practice Alert reviews 3 additional updates: 1) a new hepatitis B (HepB) vaccine; 2) updated recommendations for the use of hepatitis A (HepA) vaccine for post-exposure prevention and before travel; and 3) inclusion of the homeless among those who should be routinely vaccinated with HepA vaccine.

Hepatitis B: New 2-dose product

As of 2015, the annual incidence of new hepatitis B cases had declined by 88.5% since the first HepB vaccine was licensed in 1981 and recommendations for its routine use were issued in 1982.² The HepB vaccine products available in the United States are 2 single-antigen products, Engerix-B (GlaxoSmithKline) and Recombivax HB (Merck & Co.). Both can be used in all age groups, starting at birth, in a 3-dose series. HepB vaccine is also available in 2 combination products: Pediarix, containing HepB, diphtheria and tetanus toxoids, acellular pertussis, and inactivated poliovirus (GlaxoSmithKline), approved for use in children 6 weeks to 6 years old; and Twinrix (GlaxoSmithKline), which contains both HepB and HepA and is approved for use in adults 18 years and older.

The HepB vaccine is recommended for all children and unvaccinated adolescents as part of the routine vaccination schedule. It is also recommended for unvaccinated adults with specific risks (TABLE 1²). However, the rate of HepB vaccination in adults for whom it is recommended is suboptimal (FIGURE),³ and just a little more than half of adults who start a 3-dose series of HepB complete it.⁴A new vaccine against hepatitis B, HEPLISAV-B (Dynavax Technologies), was licensed by the US Food and Drug Administration in late 2017. ACIP now recommends it as an option along with other available HepB products. HEPLISAV-B is given in 2 doses separated by 1 month. It is hoped that this shortened 2-dose series will increase the number of adults who achieve full vaccination. In addition, it appears that HEPLISAV-B provides higher levels of protection in some high-risk groups—those with type 2 diabetes or chronic kidney disease.³ However, initial safety studies have shown a small absolute increase in cardiac events after vaccination with HEPLISAV-B. Post-marketing surveillance will be needed to show whether this is causal or coincidental.³

If a HepB series must be completed with different products, just be sure 3 doses are given—even if HEPLISAV-B is one of the agents.

As with other HepB products, use of HEPLISAV-B should follow the latest CDC directives on who to test serologically for prior immunity, and on post-vaccination testing to ensure protective antibody levels were achieved.² It is best to complete a HepB series with the same product, but, if necessary, a combination of products at different doses can be used to complete the HepB series. Any such combination should include 3 doses, even if one of the doses is HEPLISAV-B.

Hepatitis A: Vaccination assumes greater importance for more people

A Practice Alert in early 2018 described a series of outbreaks of hepatitis A around the country and the high rates of associated hospitalizations.⁵ These outbreaks have occurred primarily among the homeless and their contacts and those who use illicit drugs. This nationwide outbreak has now spread, resulting in more than 7500 cases since July 1, 2016.⁶ The progress of this epidemic can be viewed on the CDC Web site (https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm).⁷ At its October 2018 meeting, ACIP added homelessness to the list of those (previously unvaccinated) who should receive the HepA vaccine (TABLE 2).⁶

Continue to: Remember that the current recommendation...

Remember that the current recommendation is to vaccinate all children 12 to 23 months old with HepA, in 2 separate doses. Two single-antigen HepA products are available: Havrix (GSK) and Vaqta (Merck). For the 2-dose sequence, Havrix is given at 0 and 6 to 12 months; Vaqta at 0 and 6 to 18 months. Even a single dose will provide protection for up to 11 years. In addition to these vaccines, there is the combination HepA and HepB vaccine (Twinrix) mentioned earlier.

Previous recommendations for preventing hepatitis A after exposure, made in 2007, stated that HepA vaccine was preferred for healthy individuals ages 12 months through 40 years, while immune globulin (IG) was preferred for adults older than 40, infants before their first birthday, immunocompromised individuals, those with chronic liver disease, and those for whom HepA vaccine is contraindicated.⁸ The 2007 recommendations also advised vaccinating individuals traveling to countries with intermediate to high hepatitis A endemicity.

A single dose of HepA vaccine was recommended for all those 12 months or older, although older adults, immunocompromised individuals, and those with chronic liver disease or other chronic medical conditions planning to visit an endemic area in ≤ 2 weeks were supposed to receive the initial dose of vaccine and could also receive IG (0.02 mL/kg) if their provider advised it. Travelers who declined vaccination, those younger than 12 months, or those allergic to a vaccine component could receive a single dose of IG (0.02 mL/kg), which provides protection up to 3 months.

Consider prescribing daily pre-exposure prophylaxis for men and women at risk from sexual exposure to HIV or who inject illicit drugs.

Several factors influenced ACIP to reconsider both the pre- and post-exposure recommendations. Regarding IG, evidence of its decreased potency over time led the committee to increase the recommended dose (see below). IG also must be re-administered every 2 months, the supply of the product is questionable, and many health care facilities do not stock it. By comparison, HepA vaccine offers the advantages of easier administration, inducing active immunity, and providing longer protection. Another issue involved infants ages 6 to 11 months traveling to an area with endemic measles transmission and who must therefore receive the measles, mumps, and rubella (MMR) vaccine. MMR and IG should not be co-administered, and, for infants, the health risk from measles outweighs that from hepatitis A.

Updated recommendations. After considering all this information, ACIP made the following changes to its hepatitis A virus (HAV) prevention recommendations (in addition to adding homeless people to the list of HepA vaccine recipients)⁹:

• Administer HepA vaccine as post-exposure prophylaxis to all individuals 12 months and older.
• IG may be administered, in addition to HepA vaccine, to those older than 40 years, depending on the provider’s risk assessment (degree of exposure and medical conditions that might lead to severe complications from HAV infection). The recommended IG dose is now 0.1 mL/kg for post-exposure prevention; it is 0.1 to 0.2 mL/kg for pre-exposure prophylaxis for travelers, depending on the length of planned travel.
• Administer HepA vaccine alone to infants ages 6 to 11 months traveling outside the United States when protection against hepatitis A is recommended.

These recommendations have been published in the Morbidity and Mortality Weekly Report.⁹

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The development of a prophylactic hepatitis C vaccine faces significant challenges, according to a Justin R. Bailey, MD, of Johns Hopkins University, Baltimore, and his colleagues.

luiscar/Thinkstock

Barriers to developing a prophylactic HCV vaccine include the great diversity of the virus, the limited models that are available for vaccine testing, and the currently incomplete understanding of protective immune responses, according to their review published in Gastroenterology.

Functionally, the inability to culture HCV, until recently, and continuing limitations of HCV culture systems pose challenges to standard production of a live-attenuated or inactivated whole HCV vaccine. In addition, there is the risk of causing HCV infection with live-attenuated vaccines.

On a practical level for all forms of vaccine development, a principal challenge “is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1,” according to the authors (Gastroenterology 2019;156[2]:418-30).

With regard to vaccine testing, there are also significant difficulties: There is a lack of in vitro systems and immunocompetent small-animal models useful for determining whether vaccination induces protective immunity. Although a use of an HCV-like virus, the rat Hepacivirus, provides a new small-animal model for vaccine testing, this virus has limited sequence analogy to HCV.

The development of immunity to HCV in humans is complex and under broad investigation. However, decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection, according to the authors, and vaccine strategies to induce all three adaptive immune responses are in development.

“A prophylactic HCV vaccine is an important part of a successful strategy for global control. Although development is not easy, the quest is a worthy challenge,” the authors concluded.

Dr. Bailey and his colleagues reported that they had no conflicts.

[email protected]

SOURCE: Bailey JR et al. Gastroenterology 2019(2);156:418-30.

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

The 2018-2019 flu season may have peaked as the major nationwide measure of influenza activity held steady for the week ending Feb. 23, according to the Centers for Disease Control and Prevention. The proportion of outpatient visits for influenza-like illness (ILI) was 5.0% for the most recent reporting week, the CDC’s influenza division said in its March 1 report. The previous week’s outpatient visit rate, originally reported as 5.1%, was revised this week to 5.0% as well, suggesting that flu activity is no longer increasing.

Activity at the state level was more mixed. The number of states at level 10 on the CDC’s 1-10 scale of ILI activity stayed at 24 as Indiana and North Dakota replaced Tennessee and Wyoming, but the number of states in the high range (8-10) of the activity scale increased from 30 to 33, CDC data show.

The signs of plateauing ILI activity did not, however, extend to flu-related deaths, with 15 reported among children – the highest weekly number for the 2018-2019 season, although 11 actually occurred in previous weeks – during the week ending Feb. 23 and 289 deaths among all ages for the week ending Feb. 16, which is already more than the 268 listed the week before despite less complete reporting (82% vs. 97%), the CDC reported. Total flu-related deaths in children are now up to 56, compared with 138 at the corresponding point in the 2017-2018 season.

[email protected]

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

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

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

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.

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.

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

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

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

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

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.

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.

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

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

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

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

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.

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.

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

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

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

A booster dose for pre-exposure prophylaxis with an anthrax vaccine may be given at 3 years after an initial series for individuals not currently at risk who wish to maintain protection, according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Carolina K. Smith, MD/Fotolia.com

In a unanimous 15-0 vote at the February meeting, ACIP committee members agreed on the recommendation after adjusting the wording to reflect a permissive, rather than mandated, guidance.

William Bower, MD, of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), presented data on Anthrax Vaccine Adsorbed (AVA) to support its protective effects over a longer booster dose interval.

The recommendations apply to persons aged 18 years or older who are not currently at high risk of exposure to Bacillus anthracis, but who might need to deploy to a high-risk area quickly, such as military personnel, Dr. Bower said.

In addition, data suggest that adults who have started, but not completed the pre-exposure priming series, can transition to the postexposure schedule prior to entering a high-risk area, he noted.

The previous pre-exposure anthrax vaccination schedule was a three-dose priming series at 0, 1, and 3 months, followed by a booster at 12 months and 18 months, then annually.

Data from several human immunogenicity studies showed a robust immune response following a delayed anthrax booster dose, with “sustained immunological memory to at least month 42,” and suggested that even longer intervals between boosters may be possible, Dr. Bower said.

A dosing schedule of intramuscular injections at 0 and at 1 month and 6 months, with a booster at 42 months yielded survival estimates of approximately 84%-93%.

Dr. Bower noted that a new vaccine, AV7909, has demonstrated safety and effectiveness similar to AVA and could be used for pre-exposure prophylaxis if AVA is not available. AVA remains the preferred option, but ultimately will be replaced by AV7909, when the current AVA stockpile is exhausted.

Additional safety data on AV7909 will be reviewed by ACIP as they become available, and future guidance from the CDC will include statements on dosing for special populations including pregnant and breastfeeding women, said Dr. Bower.

“We anticipate that this [anthrax vaccine] work group will reconvene in 2021 to review data from pending studies” of AV7909, he said.

The ACIP members had no financial conflicts to disclose.

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

Vaccination against Japanese encephalitis is recommended for persons moving to endemic areas, or who travel to these areas frequently or for long-term visits, according to a vote at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus and those at risk for infection include travelers to countries where JE is endemic, as well as laboratory personnel who work with the virus.

The committee voted unanimously 15-0 in favor of the recommendations, which also advised vaccination for those whose travels in endemic areas are uncertain, but not for travelers with low-risk itineraries “such as shorter term travel limited to urban areas or travel that occurs outside of a well-defined JE virus transmission season.”

Susan Hills, MD, of the of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, presented data in support of the recommendations.

A second unanimous vote confirmed recommendations for a primary series schedule for JE vaccination for adults aged 18-65 years as “two doses of vaccine administered on days 0 and 7-28.”

The third vote, also a unanimous 15-0, updated recommendations for a JE booster dose. The new recommendation is that adults and children receive a booster dose (a third dose) at least a year after completion of the primary JE vaccine series “if ongoing exposure or re-exposure to JE virus is expected.”

The currently available Japanese encephalitis vaccine in the United States is an inactivated Vero cell culture-derived vaccine marketed as IXIARO that was approved in March 2009 for individuals aged 17 years and older and approved in May 2013 for children aged 2 months through 16 years.

The ACIP members had no financial conflicts to disclose.
 

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

[email protected]

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

[email protected]

Officials from the Centers for Disease Control and Prevention and the National Institute for Allergy and Infectious Diseases stressed the safety of measles vaccines and warned that misinformation is among the factors keeping more children from being vaccinated.

Courtesy House Energy and Commerce Committee

With nearly 160 cases of measles in 10 states during Jan. 1–Feb. 21, a disease once eradicated from the United States is resurfacing, with most cases affecting those who have not been vaccinated.

“Measles outbreaks have been and continue to be a constant threat to the health of the American people,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, testified at a Feb. 27 hearing of the Oversight and Investigations Subcommittee of the House Energy and Commerce Committee.

She noted that unvaccinated Americans traveling abroad are at risk for contracting the infection, and thus are at risk of spreading it when they return home. Foreigners coming to the country also carry the potential to spread the infection.

“Nationally, we enjoy high measles vaccination coverage,” Dr. Messonnier said.”There are pockets of people who are vaccine hesitant, who delay or even refuse to vaccinate themselves and their children. Outbreaks of measles occur when measles gets into these communities of unvaccinated people.”

She noted that those who eschew vaccination tend to live near one another and share common religious beliefs or racial or ethnic backgrounds.

She continued that vaccine hesitancy “is the result of the misunderstanding of the risk and seriousness of disease, combined with misinformation of the safety and effectiveness of vaccines. However, the specific issues fueling hesitancy varies by community.”

Strategies to increase vaccination need to be localized with national support from the CDC, Dr. Messonnier said, adding that rapid response is critical to control outbreaks.

Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases at NIH, agreed.

“I consider it really an irony that you have one of the most contagious viruses known to man juxtaposed against one of the most effective vaccines that we have and yet we don’t do and have not done what could be done, namely completely eliminate and eradicate this virus,” Dr. Fauci said.

Dr. Messonnier stressed that the only way to protect against measles is to get vaccinated.

“If they have questions, they should talk to their doctor,” she added. “Their doctor can provide them with more information about measles, answer their questions and reassure them so they go ahead and get vaccinated.”

Dr. Fauci concurred and added that “we should look upon it in two approaches. One, it’s for the safety of your own child. The other is a responsibility to the community. ... We all have a responsibility to be part of that umbrella of herd immunity and once it goes down below a certain percentage, then you have danger to the entire society.”

He stressed that the CDC is a good website to combat much of the misinformation that is floating around on the Internet.

The committee panel, while taking an interest in the recent outbreaks, did not hint at any specific legislative actions were being considered.
 

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