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

Abstract

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. Cervical specimens, collected before LEEP and at 6-month study visits, were tested by L1-PCR for detection of >or=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. 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 alpha3 species [all are noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the alpha9 (HPV16 and related types) and alpha7 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 alpha3 species (22.6%) were the most likely to reappear compared with HPV types in the alpha9 (7.5%) and alpha7 (6.8%) species. 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 alpha3 species, which are in effect not treated, but are not associated with cervical cancer and are unlikely to cause disease.