The grades of evidence (I-III) and levels of recommendation (A-C) are defined at the end of the "Major Recommendations" field.
The following recommendations are based on good and consistent scientific evidence (Level A):
- Premenopausal women 21 years and older with atypical squamous cells of undetermined significance (ASC-US) cytology results may undergo immediate colposcopy or may undergo triage testing to determine which of them should be referred to colposcopy. Triage testing may be performed by a single test for high-risk (oncogenic) types of human papillomavirus (HPV) or by repeat cytology screening at 6 months and 12 months. When the index cytology test specimen was obtained by liquid-based cytology or when an HPV specimen was co-collected, "reflex" HPV testing is the preferred approach.
- Colposcopy is recommended in premenopausal women 21 years and older with ASC-US who are HPV positive, those with two consecutive ASC-US cytology results or with low grade squamous intraepithelial lesions (LSIL), or women of any age with atypical squamous cells, cannot exclude high grade squamous intraepithelial lesions (ASC-H).
- For premenopausal women 21 years and older with an HPV-positive ASC-US, or ASC-H or LSIL cytology result in whom cervical intraepithelial neoplasia (CIN) grades 2,3 is not identified, follow-up without treatment is recommended using either repeat cervical cytology tests at 6 months and 12 months or an HPV test at 12 month-intervals; a repeat colposcopy is indicated for a cytology result of ASC-US or higher-grade abnormality or a positive high-risk HPV test result. After two consecutive negative cytology results or one negative HPV result women can return to routine screening.
- In women 21 years and older with HSIL cytology results, immediate loop electrosurgical excision or colposcopy with endocervical assessment are both acceptable management options. In adolescents and pregnant women with HSIL cytology results, colposcopy is recommended. Immediate excision is not acceptable in adolescents and pregnant women. A diagnostic excisional procedure is recommended for all nonpregnant women with HSIL when colposcopy is unsatisfactory or when CIN of any grade is identified on endocervical assessment.
- Posttreatment management options for women 21 years and older who have CIN 2,3 include a single human papillomavirus deoxyribonucleic acid (HPV DNA) test at 6–12 months, cytology alone at 6-month intervals or a combination of cytology and colposcopy at 6-month intervals. For adolescents who have undergone treatment, cytology follow-up is preferred. Colposcopy with endocervical sampling is recommended for women who are HPV DNA positive or have a result of ASC-US or greater on repeat cytology. If the HPV DNA test is negative or if two consecutive repeat cytology test results are negative, routine screening commencing at 12 months is recommended for at least 20 years.
The following recommendations are based on limited and inconsistent scientific evidence (Level B):
- Women 21 years or older with ASC-US who test negative for HPV, or whose HPV status is unknown and who test negative for abnormalities using colposcopy, should have a repeat cytology test in 1 year. Women with ASC-US who have two negative results on repeat cytology at 6-month intervals can return to routine screening.
- In adolescents (before age 21 years) with ASC-US or LSIL cytology results, or CIN 1 histology results preceded by ASC-US or LSIL or atypical glandular cells not otherwise specified (AGC-NOS) cytology results, follow-up is recommended at 12-month intervals. At the first follow-up visit (at 12 months), only adolescents with HSIL or greater on the repeat cytology should be referred to colposcopy. At the 24-month follow-up, those with an ASC-US or greater result should be referred to colposcopy. Human papillomavirus DNA testing is unacceptable for adolescents. If HPV testing is inadvertently performed, a positive result should not influence management.
- In nonpregnant women with ASC and LSIL cytology results who are undergoing colposcopy, endocervical sampling using a brush or curette is preferred for women in whom no lesions are identified and those with an unsatisfactory colposcopy results. Endocervical sampling is acceptable for women with satisfactory colposcopy results and a lesion identified in the transformation zone. Endocervical assessment either with colposcopy or by sampling is recommended for all nonpregnant women with HSIL cytology results. Endocervical curettage is unacceptable in pregnant women.
- The recommended management of pregnant women with a histology diagnosis of CIN 1 is follow-up without treatment. Treatment of pregnant women for CIN 1 is unacceptable.
- In a woman 21 years and older with CIN 1 that has persisted for at least 2 years, either continued follow-up or treatment is acceptable. If treatment is selected and the colposcopy result is satisfactory, either excision or ablation is acceptable. If treatment is selected and the colposcopy examination is unsatisfactory, the ECC is positive, or the woman has been previously treated, excision is recommended and ablative procedures are unacceptable.
- Pregnant women with biopsy-proven CIN 2 or CIN 3 in whom there is no suspicion of invasive cancer may postpone re-evaluation with cytology and colposcopy to no sooner than 6 weeks postpartum. Treatment during pregnancy is unacceptable unless invasion is suspected. When invasion is suspected, a diagnostic excisional procedure is recommended.
- For women 21 years and older, the preferred management of CIN 2,3 identified at the margins of a diagnostic excisional procedure or in an endocervical sample obtained at the end of the procedure is reassessment using cytology with endocervical sampling at 4 to 6 months following treatment. Performing a repeat diagnostic excisional procedure is acceptable, as is a hysterectomy if a repeat diagnostic procedure is not feasible and for women with a histology diagnosis of recurrent or persistent CIN 2,3.
- In nonpregnant women 21 years and older, both excision and ablation are acceptable treatment modalities in the presence of histology diagnoses of CIN 2,3 and satisfactory colposcopy results. Ablation is unacceptable when colposcopy has not been performed, the endocervical sampling is positive for any grade of CIN, the colposcopy result is unsatisfactory, or a woman has recurrent CIN 2,3.
- Colposcopy with endocervical sampling is recommended and HPV DNA testing is preferred for women with all subcategories of AGC and adenocarcinoma in situ (AIS). In addition, endometrial sampling is recommended in women 35 years and older and in women younger than 35 years with clinical indications suggesting they may be at risk of neoplastic endometrial lesions (e.g., unexplained vaginal bleeding, chronic anovulation, or atypical endometrial cells). Colposcopy can be performed either at the initial evaluation or after the results are known. If no endometrial pathology is identified, colposcopy is recommended. Endometrial and endocervical sampling are unacceptable in pregnant women.
- Women 21 years and older with either atypical endocervical, endometrial, or glandular cells NOS who do not have CIN or glandular neoplasia identified histologically should receive repeat cytology testing combined with HPV DNA testing at 6 months if they are HPV DNA positive and at 12 months if they are HPV DNA negative. Referral to colposcopy is recommended for women who subsequently test positive for high-risk HPV DNA or who are found to have ASC-US or greater on their repeat cytology tests. If both tests are negative, women can return to routine cytology testing.
- Women with AGC, favors neoplasia or AIS cytology results should undergo a diagnostic excisional procedure unless invasive disease is identified during the initial colposcopy workup. The diagnostic excisional procedure used in this setting should provide an intact specimen with interpretable margins. Concomitant endocervical sampling is preferred, except in pregnant women.
- Hysterectomy is unacceptable as the primary therapy for CIN.
- Diagnostic ablation or excision is unacceptable as the initial management for ASC or LSIL.
The following recommendations are based primarily on consensus and expert opinion (Level C):
- In nonpregnant women 21 years and older with HSIL in whom CIN 2,3 has not been identified, three management options are acceptable: diagnostic excisional procedure; review of the cytology, histology, and colposcopy findings and management of the patient according to the revised interpretation; or if the colposcopy is satisfactory and endocervical sampling is negative, observation with colposcopy and cytology at 6 month-intervals for 1 year. A diagnostic excisional procedure is recommended for women with repeat HSIL cytology results at either the 6-month or 12-month visit. Women with two consecutive negative cytology results can return to routine screening.
- In adolescents (before age 21 years) with HSIL cytology results, a satisfactory colposcopy result, negative endocervical sampling, and no CIN 2,3 identified on colposcopy biopsy, follow-up is recommended at 6-month intervals with Pap testing and colposcopy for up to 24 months. If during follow-up a high grade colposcopy lesion is identified or HSIL cytology results persist for 1 year, biopsy is recommended. If HSIL persists for 24 months without identification of CIN 2,3, or if the colposcopy result is unsatisfactory, a diagnostic excisional procedure is recommended. After two consecutive negative cytology results, women can return to routine cytology testing.
- For adolescents and young women with a histology diagnosis of CIN 2,3 NOS and a satisfactory colposcopy result either treatment or observation for up to 24 months using both colposcopy and cytology at 6-month intervals is acceptable. When a histology diagnosis of CIN 2 is specified, observation is preferred. When a histology diagnosis of CIN 3 is specified or when the colposcopy result is unsatisfactory, treatment is recommended. If the colposcopy appearance of the lesion worsens or if an HSIL cytology result or a high-grade colposcopy lesion persists for 1 year, repeat biopsy is recommended. After two consecutive negative cytology results, women with normal colposcopy results can return to routine cytology screening. Treatment is recommended if CIN 3 is subsequently identified or if CIN 2,3 persists for 24 months.
- In nonpregnant women 21 years and older with HSIL or AGC-NOS cytology results in whom CIN 1 has been identified on colposcopy three management options are acceptable: diagnostic excisional procedure; review of the cytology, histology, and colposcopy findings and management of the patient according to the revised interpretation; or if the colposcopy is satisfactory and endocervical sampling is negative, observation with colposcopy and cytology at 6-month intervals for 1 year. A diagnostic excisional procedure is recommended for women with repeat HSIL cytology results at either the 6-month or 12-month visit. Women with two consecutive negative cytology results can return to routine cytology screening.
- In women 21 years and older with atypical endocervical, endometrial, or glandular cells NOS, HPV DNA testing is preferred at the time of colposcopy (if not already performed). For women of unknown HPV status who do not have CIN or glandular neoplasia identified histologically, the recommended postcolposcopy management is to repeat cytology testing at 6-month intervals. After four consecutive negative cytology results, women can return to routine cytology testing.
- Women with a cervical biopsy diagnosis of AIS should undergo excision to exclude invasive cancer. A conization technique that preserves specimen orientation and permits optimal interpretation of histology and margin status is recommended. After conization, hysterectomy is preferred for women who have completed childbearing. Conservative management is acceptable if the margins of the specimen and the postprocedure endocervical curettage results are negative and future fertility is desired. If conservative management is planned and the margins of the specimen are involved or the postprocedure endocervical curettage specimen contains CIN or AIS, re-excision is preferred. Reevaluation at 6 months using a combination of cervical cytology, HPV DNA testing, and colposcopy with endocervical sampling is acceptable in this circumstance. Long-term follow-up after treatment is recommended for all women with AIS.
Definitions:
Grades of Evidence
I: Evidence obtained from at least one properly designed randomized controlled trial.
II-1: Evidence obtained from well-designed controlled trials without randomization.
II-2: Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.
II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments also could be regarded as this type of evidence.
III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
Levels of Recommendations
Level A — Recommendations are based on good and consistent scientific evidence.
Level B — Recommendations are based on limited or inconsistent scientific evidence.
Level C — Recommendations are based primarily on consensus and expert opinion.