College of American Pathologists
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cap today

January 2004
Special Section

Management schemes for minimally abnormal cervical smears

Emily E. Volk, MD, and David C. Wilbur, MD

Even as we struggle to keep up with innovations highlighted in pathology-focused journals, we need to be aware of clinically focused literature that may significantly alter how our clinical colleagues practice and potentially change their laboratory needs. Five such works, which dramatically affect the clinical practice of cervical cancer prevention, were recently published.

Four landmark papers were featured in the American Journal of Obstetrics and Gynecology (2003;188: 1383-1392, 1393-1400, 1401- 1405, 1406- 1412). The papers are part of the National Cancer Institute’s recently completed ASCUS-LSIL Triage Study, or ALTS, investigating the use of three management schemes for triaging minimally abnormal cervical smears. These smears represent a significant caseload and hence a large burden on the medical system. The overriding goal of the ALTS trial was to identify which of the three management strategies was most effective in terms of sensitivity for detecting high-grade precursor lesions and in terms of cost and time.

The ALTS trial tested three management strategies for minimally abnormal specimens: immediate colposcopy, human papillomavirus triage with referral for colposcopy if positive for high-risk HPV, and conservative management, defined as followup with repeat cervical smears with colposcopy only for an interpretation of high-grade squamous intraepithelial lesion on these cytology specimens. The strengths of this trial included its large sample size-5,060 women treated at four large clinical centers enrolled in the study from January 1997 to December 1998-and its masked, prospective nature. The data, the heart of which is presented in the four papers, provide the medical community with comparisons of outcomes based on the three management strategies.

The results demonstrate that high-risk HPV testing is the most effective method of triage for ASC-US cytology results. In fact, a single enrollment HPV test would have triaged 92 percent of women who were ultimately found to have CIN 3, while referring only 53 percent of the total ASC-US population. For the conservative management arm, at least two repeat cytology specimens would have been necessary to achieve the same sensitivity, but this strategy would have shown a colposcopy referral rate of 67 percent. Interestingly, the immediate colposcopy arm of the study detected less CIN 3 than did the HPV testing arm, suggesting that awareness of a positive HPV result may lead the operator to perform a more sensitive cervical examination. With regard to risk of subsequently developing CIN 2 or 3, the trial data show that patients with ASC-US who test positive for high-risk HPV are clinically equivalent to those with initial cytologic interpretations of low-grade squamous intraepithelial lesion. This risk of developing CIN 2 or 3 is approximately 27 percent over two years.

The other landmark guideline with which all pathologists interpreting cervical smears should be familiar is "2001 consensus guidelines for the management of women with cervical cytological abnormalities" (Wright TC, et al. JAMA. 2002; 287: 2120- 2129). A panel of 121 experts was invited to participate in a conference sponsored by the American Society for Colposcopy and Cervical Pathology. One of the panel’s most significant conclusions was that the selection of management for women having atypical squamous cells should depend on subcategorization into ASC-US or ASC-H (atypical squamous cells, cannot exclude high-grade dysplasia). Women with ASC-US may be managed with a program of two repeat cytology tests, immediate colposcopy, or HPV-DNA testing. (The latter is preferred when the specimen is processed by the liquid-based method.) Patients whose tests are interpreted as ASC-H, LSIL, HSIL, or atypical glandular cells should be referred for colposcopic evaluation.

This summary provides pathologists with the most up-to-date guide to clinicians’ likely management of abnormal cervical smear interpretations. Pathologists may find it useful to share these references with their clinical colleagues to ensure that optimal management guidelines are available at all levels of practice.

Dr. Volk, a member of the CAP Cytopathology Committee, is staff pathologist at William Beaumont Hospital, Troy, Mich. Dr. Wilbur, chair of the Nongynecologic Working Group of the CAP Cytopathology Committee, is director of cytology at Massachussetts General Hospital, Boston.