Assessing the Clinical Significance of HPV Quantitation in HIV-Associated Anal Dysplasia

Abstract

Approximately 90% of anal cancers and nearly 100% of cervical cancers are associated with human papillomavirus (HPV) infection of epithelial cells. Although most sexually transmitted HPV infections are asymptomatic and are cleared by the immune system within 1-2 years. Unresolved infections can present themselves as genital warts or anal neoplasia as lowgrade squamous cell intraepithelial lesions (LSILs), atypical squamous cells of undetermined significance (ASCUS), atypical squamous cells of undetermined significance but can’t rule out HSIL (ASC-H), and high-grade squamous cell intraepithelial lesions (HSILs) resulting from an anal cytology screen. Human immunodeficiency virus, type 1 (HIV)-positive men and women have a 52 times and 14 times higher risk of increased risk of invasive anal cancer and should therefore receive annual anal cytology screening tests as part of their routine health maintenance. The objective of this study was to assess the clinical significance of HPV quantitation in HIV-associated anal dysplasia, which could possibly be incorporated into the current anal cancer diagnostic algorithm. Anal cytology samples were used in this study to detect and quantitate high-risk HPV subtypes 16 and 18, which are associated with roughly 70% of anal dysplasia and anal cancer cases in the United States. Preliminary results indicate that HPV 16 is significantly associated with atypical cytology (p= 0.0298) but HPV 18 is not significantly associated with atypical cytology (P=0.9984). We observed in a higher median HPV 16 copy number in HSIL and ASC-H and a lower median HPV 16 copy number in ASCUS and NEG. The parent study (RMATRIX) is continuing specimen collection to increase the sample size and determine the statistical significance of HPV 16 and 18 copy number according to cytology grades.