Shortly after the National Cancer Institute’s Bethesda 2001 meeting to modify cervical cytologic terminology,¹ the American Society for Colposcopy and Cervical Pathology (ASCCP)² developed evidence-based guidelines for the management of abnormal cervical cytologic results. These guidelines are presented in this issue of American Family Physician,³ and a simplified algorithm-based version of the recommendations is available online athttp://www.asccp.org.⁴ All physicians who perform cervical cancer screening should implement these recommendations, which now are considered the standard of care. Guidelines for managing histologically confirmed cervical intraepithelial neoplasia (CIN) also were developed for health care providers who perform colposcopy and relevant surgical interventions.⁵

The ASCCP cytologic guidelines specifically considered management of low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical glandular cells (AGC), and atypical squamous cells (ASC, subcategorized into ASC of undetermined significance [ASC-US] and ASC that cannot exclude a high-grade intraepithelial lesion [ASC-H]).

Women with changes less severe than ASC generally do not require colposcopy. However, women with ASC-H or more severe results (i.e., LSIL, HSIL, AGC, cancer) should be examined by colposcopy. Postmenopausal, adolescent, and pregnant women may be managed more conservatively.

Several options are available for women with ASC-US, which may be evaluated in one of three ways. If the Papanicolaou (Pap) test was collected using liquid-based cytology, reflex testing of residual cells using a test for 13 types of high-risk human papillomavirus (HPV) DNA is the preferred management option (Hybrid Capture 2 High-Risk HPV DNA test, Digene Corp., Gaithersburg, Md.).^6,7 Women with a positive high-risk HPV DNA test result should be evaluated with colposcopy.

Two important points about HPV DNA testing must be understood. First, the low-risk DNA test should not be used for clinical triage of women with ASC-US. This test is designed to detect nononcogenic HPV types and therefore has no utility as a triage test for CIN. Second, the high-risk test should not be used to determine how cytologic abnormalities more severe than ASC-US should be managed. Because the majority of women with LSIL or more severe cytologic changes are infected with high-risk HPV DNA types, there is no need to use the HPV DNA test to determine if a patient is at increased risk for significant neoplasia.

Colposcopy is an acceptable management option in women with ASC-US because approximately 25 percent of these women will have a cervical neoplasia. Serially repeated Pap tests also are an acceptable form of follow-up in women with ASC-US. If a repeat Pap test detects ASC-US or a more severe cytologic change, the patient should be examined by colposcopy. Serial cytologic evaluation is less robust than using a test for high-risk HPV DNA or colposcopy. Consequently, it is questionable whether serial cytologic testing will remain an acceptable option in future management guidelines.

In the past, some women were monitored after colposcopy by serial cytologic testing or cytologic testing combined with colposcopy. Several new follow-up approaches are now recommended. In women with minor cytologic changes, only two negative Pap test results are required before patients can return to a routine testing interval. Because of the more ominous nature of glandular lesions, women with AGC must have four negative follow-up cytologic test results before resuming routine Pap testing. Women with ASC-US, ASC-H, and LSIL results and no evidence of cervical neoplasia following colposcopic examination may have repeat cytology at six and 12 months or testing for high-risk HPV DNA in 12 months. The latter approach minimizes patient follow-up and allows time for regression of HPV-related lesions. Persistent HPV infection is a significant risk for the development of CIN. Because the HPV DNA test has a high negative predictive value (approximately 99 percent), a negative high-risk HPV DNA test result offers reassurance that the patient does not have a significant cervical neoplasia (CIN grade 3 or greater).

The management of AGC is vastly different from that of ASC. Although both diagnoses refer to “atypical” cells, women with AGC must have a more aggressive evaluation with colposcopy, endocervical sampling and, in some cases, endometrial biopsy. Because of the more inaccessible nature of glandular (columnar) cells within the endocervical canal and the colposcopic subtlety of these inconspicuous lesions, only experts should attempt to manage possible glandular neoplasia.

Additional educational information may be obtained from the ASCCP (telephone: 800-787-7227; Web site:http://www.asccp.org).