Penile microbiota dysbiosis associates with subclinical HPV infection in HIV-negative men

Abstract

Background

Human papillomavirus (HPV) is the most frequent sexually transmitted virus, with high importance due its oncogenic risk. Previous studies have reported an association between genital dysbiosis and HPV infection in women and also in men co-infected with HPV and HIV. However, it remains to be determined whether penile skin dysbiosis is associated with HPV infection in men who are HIV-negative. This study characterizes the penile skin microbiota (PSM) of HPV-positive and HPV-negative men, hypothesizing that HPV infection is linked to dysbiotic anaerobic-dominated communities.

Methods

A cross-sectional study was conducted on 103 sexually active HIV-negative men (70 HPV-negative, 33 HPV-positive). Those who tested HPV-positive were genotyped. The PSM of all samples was analyzed using 16S rRNA sequencing of the V4 region. Alpha and beta diversity were compared. Community State Types (CSTs) were identified using hierarchical clustering. Associations between CSTs and HPV status were tested adjusting for sexual preference.

Results

HPV-positive men exhibited significantly higher microbial richness than HPV-negative men (Chao1 p = .02), particularly those with high-risk genotypes (Chao1 p = .03). Five CSTs were identified, with CST-5 (dominated by Finegoldia and other anaerobes) showing a three-fold higher likelihood of HPV positivity (OR = 3.11, 95% CI: 1.22–8.22) compared to other CSTs. CST-5 also displayed reduced abundance of commensals like Corynebacterium and Staphylococcus.

Conclusions

Subclinical HPV infection in HIV-negative men was associated with a dysbiotic PSM, characterized by an increased abundance of anaerobic bacteria alongside with a reduced proportion of facultative anaerobic genera. These findings suggest that PSM composition may influence HPV susceptibility or persistence. Longitudinal studies are needed to explore causality.