Abstract
Objective: This study was undertaken to compare alternative strategies for the initial management
of a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS).
Study Design: A total of 3488 women with a community-based ASCUS interpretation were randomly assigned
to immediate colposcopy, triage that was based on enrollment HPV DNA testing and liquid-based
cytology at a colposcopy referral threshold of high-grade squamous intraepithelial
lesion (HSIL), or conservative management based on repeat cytology at a referral threshold
of HSIL. All arms included 2 years of semiannual follow-up and colposcopy at exit.
Loop electrosurgical excision procedure was offered to women with histologic diagnoses
of cervical intraepithelial neoplasia (CIN) grade 2 or 3 at any visit or persistent
CIN grade 1 at exit. The study end point was 2-year cumulative diagnosis of CIN grade
3. Results: The 2-year cumulative diagnosis of CIN grade 3 was 8% to 9% in all study arms. The
immediate colposcopy strategy yielded 53.6% sensitivity for cumulative cases of CIN
grade 3 diagnosed over 2 years. The human papillomavirus (HPV) triage strategy referred
55.6% of women and detected 72.3% of cumulative cases of CIN grade 3. A conservative
management strategy of repeat cytology at the HSIL threshold referred 12.3% of women
while detecting 54.6% of cumulative CIN grade 3. To compare triage tests, we re-estimated
the performance of HPV and cytology in successfully referring women with underlying
CIN grade 3 (ie, ignoring the insensitivity we discovered in colposcopically directed
biopsies). A single enrollment HPV test identified 92.4% of the women diagnosed with
CIN grade 3. Serial cytology, even at an ASCUS threshold, would have required two
visits to achieve similar sensitivity (95.4%) and would have referred 67.1% to colposcopy.
Conclusion: HPV triage is at least as sensitive as immediate colposcopy for detecting CIN grade
3 and refers about half as many women to colposcopy. Follow-up that used repeat cytology
is sensitive at an ASCUS referral threshold but requires two follow-up visits and
ultimately more colposcopic examinations than HPV triage. (Am J Obstet Gynecol 2003;188:1383-92.)
Keywords
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Article Info
Publication History
Accepted:
March 25,
2003
Received in revised form:
February 12,
2003
Received:
December 20,
2002
Footnotes
☆Supported by the National Cancer Institute, National Institutes of Health Department of Health and Human Services contracts No. CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105. Some of the equipment and supplies used in this study were donated or provided at reduced cost by Digene Corporation, Gaithersburg, Md; Cytyc Corporation, Boxborough, Mass; National Testing Laboratories, Fenton, Mo; Denvu, Tucson, Ariz; and TriPath Imaging, Inc, Burlington, NC.
☆☆Reprint requests: Diane Solomon, MD, Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, NIH, DHHS, Executive Plaza North, Room 2123, Rockville, MD 20852. E-mail: [email protected]
★*A complete list of ALTS investigators begins on page 1411.
Identification
Copyright
© 2003 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
