Increased risk of high-grade anal neoplasia associated with a human papillomavirus type 16 E6 sequence variant

Expression of the E6 and E7 genes of human papillomavirus (HPV) type 16 have been implicated in the etiology of anogenital premalignant and malignant lesions. To evaluate whether variations in the HPV-16 E6 sequence were related to the incidence of high-grade anal neoplasia, 628 HPV-16-positive anal specimens from 193 human immunodeficiency virus (HIV)-positive and 59 HIV-negative participants were typed for variations in 15 E6 nucleotide positions. Although most participants were infected with a prototype strain, 15 (6%) carried the G131 variant, and 12 (5%) were infected with the Af1a variant. Two new variants not previously reported were identified as well. An elevated risk for high-grade anal squamous intraepithelial lesions was associated with infection by G131 variants, compared with the prototype strain (odds ratio, 3.4; 95% confidence interval, 1.1-10), after controlling for HIV status. These data provide further evidence for HPV strain variation as a factor in determining the natural history of anogenital neoplasia.