A rigorous exploration of anal HPV genotypes using a next‐generation sequencing (NGS) approach in HIV‐infected men who have sex with men at risk for developing anal cancer

Abstract

Abstract Background There are no HPV‐based measures for managing anal cancer (AC) in HIV‐infected (HIV+) men who have sex with men (MSM) because of the high positivity of high‐risk (HR)‐HPVs. As next‐generation sequencing (NGS) is able to describe the composition of HPVs as percent (%) reads rather than positive vs negative results, we used NGS approach to detect HPVs in anal samples of HIV+ MSM to test its ability to differentiate those who are diagnosed with atypical squamous cells of unknown significance or greater (ASCUS+) from those who are free of such lesions and to understand the burden of HPV infections in relation to HPV vaccines. Methods Study included 81 HIV+ MSM characterized for demographics, patient‐reported outcome measures, HIV related laboratory measures and anal cytology. We summarized NGS HPV data using % read cut points (>0%‐>30%) and tested the relationship between % reads of HR‐HPVs and risk of ASCUS+ using logistic regression. Results Forty‐six HPVs were detected at the >0% read cut point. The prevalence of any HR‐HPVs varied from 100% to 40% with >0% to >30% reads while ≥99% were infected with HR‐HPVs included or not included in the 9 valent HPV vaccine at the >0% read cut point. MSM with >30% HR‐HPV reads were 4.5 times more likely to be diagnosed with ASCUS+ compared to ≤30% reads (P = .033). Conclusion NGS‐based approach is more accurate than PCR‐based HPV testing for identifying HIV+ MSM at risk for developing AC. We raise the concern regarding the efficacy of current HPV vaccines for preventing AC in this high‐risk population.

Keywords

• anal cytology
• HIV
• HPV
• MSM
• next‐generation sequencing