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Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.
Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.
In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.
Terminology
The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.
In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).
With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.
Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.
Diagnosis
There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.
If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.
Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.
HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.
Management
Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.
If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.
There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.
In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).
The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.
Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.
Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].
Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.
Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.
In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.
Terminology
The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.
In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).
With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.
Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.
Diagnosis
There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.
If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.
Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.
HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.
Management
Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.
If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.
There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.
In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).
The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.
Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.
Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].
Cervical intraepithelial neoplasia (CIN) describes a precancerous lesion of the squamous epithelium of the ectocervix. The cervical cancer screening paradigm in the United States begins with collection of cervical cytology with a Pap smear, frequently in conjunction with human papillomavirus testing. Abnormalities will frequently lead to colposcopy with directed biopsy, which can result in a diagnosis of CIN. There are different grades of severity within CIN, which aids in making treatment recommendations.
Pregnancy is a convenient time to capture women for cervical cancer screening, given the increased contact with health care providers. Routine guidelines should be followed for screening women who are pregnant, as collection of cervical cytology and human papillomavirus (HPV) cotesting is safe.
In women who have been found to have abnormal cytology, CIN or malignancy has been identified in up to 19% of cases (Am J Obstet Gynecol. 2004 Jul;191[1]:105-13). High-grade lesions identified in pregnant women create a unique management dilemma.
Terminology
The Bethesda system describes colposcopic abnormalities as CIN and divides premalignant lesions into grades from 1 to 3 with the highest grade representing more worrisome lesions. CIN2 has been found to have poor reproducibility and likely represents a mix of low- and high-grade lesions. In addition, there is concern that HPV-associated lesions of the lower anogenital tract have incongruent terminology among different specialties that may not accurately represent the current understanding of HPV pathogenesis.
In 2012, the Lower Anogenital Squamous Terminology (LAST) project of the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology (ASCCP) advocated for consistent terminology across all lower anogenital tract lesions with HPV, including CIN (Int J Gynecol Pathol. 2013 Jan;32[1]:76-115).
With this new terminology, CIN1 is referred to as low-grade squamous intraepithelial lesion (LSIL). CIN2 is characterized by its p16 immunostaining; lesions that are p16 negative are considered LSIL, while those that are positive are considered HSIL (high-grade squamous intraepithelial lesion). While this staining is not universally performed, physicians will start seeing p16 staining results with increasing frequency on their cervical biopsies. CIN3 lesions are referred to as HSIL.
Given the current understanding of HPV-mediated disease, and a commitment to represent the most up-to-date information, the LAST project terminology of HSIL to represent previously identified CIN2 and CIN3 lesions will be used for the remainder of this text.
Diagnosis
There is little data on the natural history of HSIL diagnosed after colposcopy, as most women get some form of therapy. The information that is available suggests that in patients with untreated HSIL, the cumulative incidence of malignancy is as high as 30% at 30 years (Lancet Oncol. 2008 May;9[5]:425-34). Treatment recommendations for excision are aimed at addressing this alarming number; however, care must be individualized, especially in the setting of pregnancy.
If abnormal cervical cytology is obtained on routine screening, appropriate patients should be referred for colposcopic exam. Physicians performing colposcopy should be familiar with the physiologic effects of pregnancy that can obscure the exam, including the increased cervical mucus production, prominence of endocervical glands, and increased vascularity.
Colposcopic-directed ectocervical biopsies have been found to be safe in pregnancy, and these women should be provided the same care as those who are not pregnant (Obstet Gynecol. 1993 Jun;81[6]:915-8). Endocervical sampling and endometrial sampling should not be performed, however, and physicians should remain dedicated to checking pregnancy tests prior to colposcopy.
HSIL cytology should prompt a biopsy in pregnancy; a decision to skip the biopsy and perform an excisional procedure in this setting is not recommended regardless of patient or gestational age. If LSIL (CIN1) is noted on biopsy, reevaluation post partum should be strongly considered, unless a suspicious lesion was felt to be inadequately biopsied.
Management
Managing HSIL in pregnancy focuses on diagnosis and excluding malignancy, while treatment can be reserved for the postpartum period. When choosing a management option, consider individual patient factors such as colposcopic appearance of the lesion, gestational age, and access to health care.
If HSIL is noted on colposcopic-directed biopsy, consider one of several options. The most conservative approach is reevaluation with cytology and colposcopy 6 weeks post partum. This is an option for patients who do not have a colposcopic exam that was concerning for an invasive lesion, were able to be adequately biopsied, and will reliably return for follow-up. Many physicians feel more comfortable with repeat cytology and colposcopy in 3 months from the original biopsy. The most aggressive management would include an excisional procedure during pregnancy.
There are varying rates of regression of biopsy-proven HSIL in pregnancy ranging from 34% to 70% (Obstet Gynecol. 1999 Mar;93[3]:359-62; Acta Obstet Gynecol Scand. 2006;85[9]:1134-7; Reprod Sci. 2009 Nov;16[11]:1034-9). Out of more than 200 patients across these three studies, just two patients were diagnosed with an invasive lesion post partum. Given the low likelihood of progression during pregnancy and the high rate of regression, an excisional procedure should be considered only in cases where there is concern about invasive carcinoma.
In cases where an invasive lesion is suspected, consider an an excisional procedure. While there is some evidence that performing a laser excisional procedure early in pregnancy (18 weeks and earlier) can be safely done, that is not the most common management strategy in the United States (Tumori. 1998 Sep-Oct;84[5]:567-70; Int J Gynecol Cancer. 2007 Jan-Feb;17[1]:127-31). In this circumstance, referral to a gynecologic oncologist is warranted where consideration can be made for performing a cold knife conization. Physicians should be aware of the increased risk of bleeding with this procedure in pregnancy and the potential for preterm birth. There is little literature to guide counseling regarding these risks, and the decision to perform an excisional procedure should be made with a multidisciplinary team (Arch Gynecol Obstet. 2016 Jan 4. doi: 10.1007/s00404-015-3980-y).
The see-and-treat paradigm is not recommended in pregnancy. Those patients with poor follow-up should still undergo colposcopic-directed biopsies prior to any excisional procedure.
Treatment recommendations in pregnancy should be made on the basis of careful consideration of individual patient factors, with strong consideration of repeat testing with cytology and colposcopy prior to an excision procedure.
Dr. Sullivan is a fellow in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Dr. Gehrig is professor and director of gynecologic oncology at the university. Dr. Sullivan and Dr. Gehrig reported having no relevant financial disclosures. Email them at [email protected].
