Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection

Abstract

BACKGROUND Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection. This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection. METHODS A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. RESULTS In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups. CONCLUSIONS A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.