Human Papillomavirus Testing Following Loop Electrosurgical Excision Procedure Identifies Women at Risk for Posttreatment Cervical Intraepithelial Neoplasia Grade 2 or 3 Disease

doi:10.1158/1055-9965.EPI-05-0845

Human Papillomavirus Testing Following Loop Electrosurgical Excision Procedure Identifies Women at Risk for Posttreatment Cervical Intraepithelial Neoplasia Grade 2 or 3 Disease

Aimée R. Kreimer1,2,
Richard S. Guido4,
Diane Solomon2,
Mark Schiffman3,
Sholom Wacholder3,
José Jeronimo3,
Cosette M. Wheeler5,
Philip E. Castle3 and
for the ASCUS-LSIL Triage Study (ALTS) Group

¹Cancer Prevention Fellowship Program, ²Division of Cancer Prevention, and ³Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; ⁴Magee-Women's Hospital of the University of Pittsburgh Health Care System, Pittsburgh, Pennsylvania; and ⁵Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico

Requests for reprints:
Aimee R. Kreimer, National Cancer Institute, NIH, 6130 Executive Boulevard, Bethesda, MD 20892-7333; Phone: 301-594-0839; Fax: 301-480-9939. E-mail: kreimera{at}mail.nih.gov.

Abstract

Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients.

Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment.

Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02).

Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies. (Cancer Epidemiol Biomarkers Prev 2006;15(5):908–14)

Footnotes

Grant support: National Cancer Institute, NIH, Department of Health and Human Services contract nos. CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105. Some of the equipment and supplies were donated or provided at reduced costs by Digene Corporation (Gaithersburg, MD), Cytyc Corporation, (Fenton, MO), Denvu (Tucson, AZ), Roche Molecular Systems (Alameda, CA), and TriPath Imaging, Inc. (Burlington, NC).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Accepted February 21, 2006.
- Received October 31, 2005.
- Revision received February 7, 2006.