Viral Determinants of Human Papillomavirus Persistence following Loop Electrical Excision Procedure Treatment for Cervical Intraepithelial Neoplasia Grade 2 or 3

doi:10.1158/1055-9965.EPI-06-0710

Viral Determinants of Human Papillomavirus Persistence following Loop Electrical Excision Procedure Treatment for Cervical Intraepithelial Neoplasia Grade 2 or 3

¹Divisions of Cancer Prevention and ²Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland and ³Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center, School of Medicine, Albuquerque, New Mexico

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

Abstract

Background: Persistent infection with carcinogenic human papillomavirus (HPV) causes cervical precancer (cervical intraepithelial neoplasia grade 2+) which, in the United States, is commonly treated using the loop electrical excision procedure (LEEP). Data from Atypical Squamous Cells of Undetermined Significance–Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV persistence and reappearance after LEEP.

Methods: Cervical specimens, collected before LEEP and at 6-month study visits, were tested by L1-PCR for detection of ≥27 HPV types. HPV persistence, defined as the same HPV type being present before and 6 months after LEEP, was evaluated by: (a) genotype, (b) carcinogenicity, and (c) phylogenetic species. HPV infections that cleared post-LEEP (the complement of persistence) were followed for reappearance of the same type.

Results: HPV infections (n = 1,130) were detected among 481 women who underwent LEEP. Overall, 20.4% [95% confidence interval (95% CI), 18.2-22.9%] of infections persisted. Assessment of heterogeneity within the three categorizations of HPV showed that phylogenetic species best fit the data. Persistence was significantly greater by HPV types in the α3 species [all are noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the α9 (HPV16 and related types) and α7 species (HPV18 and related types; 17.6% and 17.9%, respectively; P < 0.001 for both). HPV reappeared in 7.8% (95% CI, 6.1-9.9%) of infections that cleared after LEEP. Infections in the α3 species (22.6%) were the most likely to reappear compared with HPV types in the α9 (7.5%) and α7 (6.8%) species.

Conclusions: Patterns of HPV persistence and reappearance following LEEP were better explained by phylogenetic rather than standard classifications. HPV types likely to persist after LEEP as well as those likely to repopulate the cervical/vaginal epithelium were those in the α3 species, which are in effect not treated, but are not associated with cervical cancer and are unlikely to cause disease. (Cancer Epidemiol Biomarkers Prev 2007;16(1):11–6)

Footnotes

↵4 Butsch-Kovacic. Relationships of HPV type, qualitative HPV viral load, and age with cytologic abnormality, in preparation.
Grant support: National Cancer Institute, NIH, Department of Health and Human Services contracts CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55105. Some of the equipment and supplies were donated or provided at a reduced cost by Digene Corp., Gaithersburg, MD; Roche Molecular Systems, Alameda, CA; Cytyc Corp., Fenton, MO; Denvu, Tucson, AZ; 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.
Note: Dr. Kreimer was a Cancer Prevention Fellow in the Division of Cancer Prevention at the time of this work.
- Accepted November 10, 2006.
- Received August 21, 2006.
- Revision received November 6, 2006.