Human papillomavirus genotypes in anal intraepithelial neoplasia and anal carcinoma as detected in tissue biopsies

Abstract

Human papillomavirus (HPV) infection strongly correlates with the development of anal intraepithelial neoplasias and carcinomas; however, few studies have characterized the distribution of the specific subtypes of the virus in the varying grades of dysplasia. This report characterizes the distribution of HPV 16/18 in surgical specimens with anal intraepithelial neoplasia (AIN) I–III and histological variants of anal carcinoma. A total of 111 anal surgical specimens with no dysplasia (10), AIN I–III (53), and anal carcinomas (48) were evaluated for the presence of high-risk HPV infection and subtyped by nested PCR or the Invader Assay. High-risk virus types were detected in progressively greater number of anal intraepithelial lesions from 56% in low grade to 88% in high grade. Type 16 was the prevalent subtype and was noted in 28% of low grade and 68% of high-grade lesions. Moderate dysplasias showed type 16 in 20%, a prevalence similar to that in low-grade lesions. The non-16/18 subtypes of the virus predominated and were present in 50% of the cases. Most (89%) squamous carcinomas were associated with high-risk viruses, 68% with type 16, a prevalence similar to that noted in high-grade dysplasia. Non-16/18 subtypes were encountered more frequently in squamous carcinomas from immunodeficient individuals (57% cases) as compared with immunocompetent individuals (18% cases). The similarity in the prevalence of type 16 in high-grade dysplasia and squamous carcinomas suggests that anal intraepithelial lesion III is the true precursor of squamous carcinoma and warrants aggressive management. Anal intraepithelial lesions II showed a virus distribution that was similar to low-grade dysplasia. In addition, a subset of these that were associated with type 16 or 18 showed progression, whereas those associated with non-16/18 subtypes regressed, thereby raising the possibility of conservative management for these lesions.