2012 asccp updated guidelines for the management of abnormal cervical cancer screening tests and cancer precursors

ASCCP Guidelines Update & S21

negative, retesting in 3 years is recommended (BII). If any test is abnormal, colposcopy with endocervical sampling is recommended (BII). If all tests are negative, routine screening is recommended for at least 20 years, even if this extends screening beyond 65 years of age (CIII). Repeat treatment or hysterectomy based on a positive HPV test is unacceptable (EII).

If CIN 2, CIN 3, or CIN 2,3 is identified at the margins of a diagnostic excisional procedure or in an endocervical sample obtained immediately after the procedure, reassessment using cytology with endocervical sampling at 4Y6 months after treatment is preferred (BII). Performing a repeat diagnostic excisional procedure is acceptable (CIII). Hysterectomy is acceptable if a repeat diagnostic procedure is not feasible (CIII).

A repeat diagnostic excisional procedure or hysterectomy is acceptable for women with a histologic diagnosis of recurrent or persistent CIN 2, CIN 3, or CIN 2,3 (BII).

CIN 2, CIN 3, or CIN 2,3 in Special Populations

Young Women (Fig. 17). For young women with a histologic diagnosis of CIN 2,3 not otherwise specified, either treatment or observation for up to 12 months using both colposcopy and cytology at 6-month intervals is acceptable, provided colposcopy is adequate. (BIII) When a histologic diagnosis of CIN 2 is specified for a young woman, observation is preferred but treatment is acceptable. If the colposcopic appearance of the lesion worsens or if HSIL cytology or a high-grade colposcopic lesion persists for 1 year, repeat biopsy is recommended (BIII).

After two consecutive negative cytology results, an additional co-test 1 year later is recommended (BIII). If the additional co-test is negative, then repeat co-testing in 3 years is recommended (BIII). Colposcopy is recommended if either the 2-year or 5-year co-test is abnormal (BIII).

Treatment is recommended if colposcopy is inadequate, if CIN 3 is specified, or if CIN 2 or CIN 2,3 persists for 24 months (BII). For women aged 21Y24 years who are treated, follow-up according to ASCCP guidelines for treated CIN 2, CIN 3, or CIN 2,3 is recommended (BIII).

Treatment is recommended if CIN 3 is subsequently identified or if CIN 2, CIN 3, or CIN 2,3 persists for 24 months (BII).

Pregnant Women. In the absence of invasive disease or advanced pregnancy, additional colposcopic and cytologic examinations are acceptable in pregnant women

with a histologic diagnosis of CIN 2, CIN 3, or CIN 2,3 at intervals no more frequent than every 12 weeks (BII). Repeat biopsy is recommended only if the appearance of the lesion worsens or if cytology suggests invasive cancer (BII). Deferring reevaluation until at least 6 weeks postpartum is acceptable (BII). A diagnostic excisional procedure is recommended only if invasion is suspected (BII). Unless invasive cancer is identified, treatment is unacceptable (EII). Reevaluation with cytology and colposcopy is recommended no sooner than 6 weeks postpartum (CIII).

ADENOCARCINOMA IN SITU (AIS)

The incidence of AIS is low but rising (90). Management of AIS is controversial, as many assumptions used to justify conservative management for women with CIN 2 and CIN 3 do not apply. For example, colposcopic changes associated with AIS can be minimal, so determining the limits of a lesion can be difficult. AIS frequently extends into the endocervical canal, complicating determination of the desired depth of excision. AIS can be multifocal and discontinuous, so negative margins on an excision specimen do not provide assurance that the disease has been completely excised. Invasive cancer cannot be excluded without a diagnostic excisional procedure.

For these reasons, total hysterectomy remains the treatment of choice in women who have completed childbearing. For women who wish to maintain fertility, observation is an option, although it carries a less than 10% risk of persistent AIS and a small risk of cancer even when excision margins are negative (91Y3). Like margin status, endocervical sampling at the time of an excisional procedure also predicts residual disease (94). Moreover, a negative HPV test after treatment identifies women at low risk for persistent or recurrent AIS (94). In 2001, knife conization was favored over loop excision because margin status and the interpretability of margins are critical to future treatment planning. In 2006, wording was changed to allow diagnostic excision using any modality, but care must be taken to keep the specimen intact and margins interpretable, avoiding fragmentation of the specimen, including ‘‘top-hat’’ serial endocervical excisions. This may require use of larger loops than those employed to excise visible squamous lesions.

Management of Women With AIS (Fig. 18)

Hysterectomy is preferred for women who have completed childbearing and have a histologic diagnosis of AIS on a specimen from a diagnostic excisional procedure

S22 & M A S S A D E T A L .

Figure 18.

(BIII). Conservative management is acceptable if future fertility is desired (AII). If conservative management is planned and the margins of the specimen are involved or endocervical sampling obtained at the time of excision contains CIN or AIS, reexcision to increase the likelihood of complete excision is preferred. Reevaluation at 6 months using a combination of co-testing and colposcopy with endocervical sampling is acceptable in this circumstance. Long-term follow-up is recommended for women who do not undergo hysterectomy (CIII).

RECOMMENDATIONS FOR FUTURE RESEARCH

Literature review for the 2012 ASCCP Consensus Guidelines Conference identified several issues important to patient management that lack high-level evidence.

Follow-up is insufficient to determine posttreatment outcomes or optimal long-term follow-up intervals for women with treated CIN 2 and CIN 3 managed with serial co-testing. Evidence to guide management of women with negative colposcopy after abnormal cytology or with CIN 1 is also scanty. The path to routine screening for these women is based on consensus expert opinion and should be modified as evidence becomes available.

Follow-up studies of women managed using HPV genotyping, p16 and other immunostains, cytogenetics, and other markers are needed to guide their incorporation into management of cervical abnormalities.

The effect of HPV vaccination on large cohorts over long periods of follow-up remains to be studied, and whether prior HPV vaccination alters natural history or management of cytologic or histologic abnormalities remains unknown. Prospective study of the negative consequences of screening, diagnosis, and treatment are needed to allow balancing of risks and benefits.

Outcomes analyses using the LAST Project’s two-tier squamous intraepithelial lesions (SIL) terminology are needed to direct how translation of three-tier CIN terminology to the two-tier terminology can be made and to define how specific management recommendations for histologic diagnoses in the two-tier system can be created (See Box 2). In particular, studies of the safety of observation for young women with histologic HSIL are needed, as reports to date have included diagnostic excision as a study endpoint. Estimates of regression and progression rates and the proportion of women who eventually require excision are needed. Long-term outcomes after apparent regression without treatment are unknown.

As the number and sophistication of tools applied to cervical cancer prevention continue to increase, the complexity of management promises to grow. Electronic medical records and bedside and pocket computers hold great promise for assisting clinicians and patients in negotiating this complexity. Development of risk scoring that incorporates past screening and treatment history into management decisions may help to balance risks and

ASCCP Guidelines Update & S23

benefits on a more individualized level than consensus guidelines. Future consensus conferences will be needed to integrate new approaches.

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APPENDIX A: ADDITIONAL COAUTHOR PARTICIPANTS, ACKNOWLEDGED NONAUTHOR DELEGATES, AND PARTICIPATING ORGANIZATIONS

See Appendix 2, available online at http://links.lww.com/ LGT/A10, for financial disclosure information from the coauthor delegates.

Coauthor Delegates: Deborah Arrindell; James R. Bentley, MD; Monique A. Bertrand, MD; Lori A. Boardman, MD; Philip E. Castle, PhD, MPH; David Chelmow, MD; Janie Daddario, MSN, WHNP-BC; Diane D. Davey, MD; Linda Dominguez, CNP, RN; Levi S. Downs, Jr., MD; Patricia Fontaine, MD, MS; Julia C. Gage, PhD, MPH; Francisco A.R. Garcia, MD, MPH; Mohiedean Ghofrani, MD, MBA; Richard S. Guido, MD; Eric C. Huang, MD, PhD; Versie JohnsonMallard, PhD, ARNP; Elizabeth A. Kostas-Polston, PhD, APRN, WHNP-BC; Robert Kurman, MD; Susan M. McFaul, MD; Deborah L. Nucatola, MD; R. Patricia P. Power, MD; Walter Prendiville, MD; Debbie Saslow, PhD; Karen Shea, MSN, WHNP-BC; Mary K. Sidawy, MD; Mario Sideri, MD; Kate Simon, PhD; Silvio Tatti, MD; Jeffrey Waldman, MD; Jason D. Wright, MD; Fred Wyand; and Laurie C. Zephyrin, MD, MPH, MBA

Nonauthor Delegates Whose Contribution is Acknowledged: Vicki B. Benard, PhD; Natalia Comella, PhD; MariBeth Gagnon, MS CT(ASCP) HTL; Ann Laros, MD; Mona Saraiya, MD, MPH; Elizabeth R. Unger, PhD, MD; and Rose H. Xu, PharmD, MSc.

Participating Organizations: American Academy of Family Physicians; American Board of Pathology; American Cancer Society; American College Health

ASCCP Guidelines Update & S27

Association; American College of Obstetricians and Gynecologists; American Social Health Association; American Society for Colposcopy and Cervical Pathology; American Society for Cytopathology; Association of Reproductive Health Professionals; CDC - Division of Cancer Prevention and Control; CDC - Division of High-Consequence Pathogens and Pathology; CDC - Division of Laboratory Science & Standards; College of American Pathologists; Food & Drug Administration; International Federation for Cervical Pathology and Colposcopy; International Gynecologic Cancer Society; National Cancer Institute; Nurse Practitioners in Women’s Health; Planned Parenthood Federation of America; Society of Canadian Colposcopists; Society of Gynecologic Oncologists; Society of Obstetricians and Gynaecologists of Canada; and Women Veterans Health Strategic Healthcare Group.

APPENDIX B: DEFINITION OF TERMS

Colposcopy is the examination of the cervix, vagina, and, in some instances the vulva, with a colposcope after the application of a 3% to 5% acetic acid solution coupled with obtaining colposcopically directed biopsies of all lesions suspected of representing neoplasia.

Adequate colposcopy indicates that the entire squamocolumnar junction and the margins of any visible lesion can be visualized with the colposcope.

Co-testing is assessment for cervical disease using a combination of cytology and HPV testing at the same time, regardless of the cytology result.

Reflex HPV testing is the performance of HPV testing only in response to an abnormality to stratify risk and guide further management.

Endometrial sampling includes obtaining a specimen for histologic evaluation using an endometrial biopsy, dilation and curettage, or hysteroscopy.

Endocervical sampling includes obtaining a specimen for either histologic evaluation using an endocervical curette or a cytobrush or for cytologic evaluation using a cytobrush.

Endocervical assessment is the process of evaluating the endocervical canal for the presence of neoplasia using either a colposcope or endocervical sampling.

Diagnostic excisional procedure is the process of obtaining a specimen from the transformation zone and endocervical canal for histologic evaluation and includes laser conization, cold-knife conization, loop or needle electrosurgical excision, and loop electrosurgical conization.

Lesser abnormalities are those that carry lower risk of CIN 3+ than other results. These include negative cytology with either HPV-16 or HPV-18 or persistent untyped oncogenic HPV, ASC-US, and LSIL.

HPV, human papillomavirus; CIN, cervical intraepithelial neoplasia; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesions.