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

¹ Divisions of Cancer Prevention and ² Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland and ³ Departments 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

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 3 species [all are noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the 9 (HPV16 and related types) and 7 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 3 species (22.6%) were the most likely to reappear compared with HPV types in the 9 (7.5%) and 7 (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 3 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)