This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kreimer, A. R. Search for Related Content PubMed PubMed Citation Articles by Kreimer, A. R.

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

¹ Cancer Prevention Fellowship Program, ² Division of Cancer Prevention, and ³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; ⁴ Magee-Women's Hospital of the University of Pittsburgh Health Care System, Pittsburgh, Pennsylvania; and ⁵ Departments 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.

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)

This article has been cited by other articles:

				A. R. Kreimer, H. A. Katki, M. Schiffman, C. M. Wheeler, P. E. Castle, and for the ASCUS-LSIL Triage Study Group Viral Determinants of Human Papillomavirus Persistence following Loop Electrical Excision Procedure Treatment for Cervical Intraepithelial Neoplasia Grade 2 or 3 Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 11 - 16. [Abstract] [Full Text] [PDF]