Metabolomic and microbiota profiles in cervicovaginal lavage fluid of women with high-risk human papillomavirus infection

The presence of high-risk human papillomavirus (HR-HPV) contributes to the development of cervical lesions and cervical cancer. Recent studies suggest that an imbalance in the cervicovaginal microbiota might be a factor in the persistence of HR-HPV infections. In this study, we collected 156 cervicovaginal fluid (CVF) of women with HR-HPV infection, which were divided into three groups (negative for intraepithelial lesions = 78, low/high-grade squamous intraepithelial lesions = 52/26). We performed metabolomics and 16 S rRNA sequencing to identify changes in metabolites and cervicovaginal microbiota among patients with HR-HPV infection and varying grades of cervical lesions. We detected 164 metabolites and 389 flora types in the three groups. Ten CVF metabolites—N-methylalanine, phenylacetaldehyde, succinic acid, 2-3-dihydroxypyridine, DL-p-hydroxylphenyllactic acid, gluconic acid lactone, guanine, glucose-6-phosphate, erythrose, and sucrose showed significant associations with disease severity and distinct separation patterns in HR-HPV-infected patients with LSIL and HSIL, with an area under the curve of 0.928. The most abundant microbial communities in the CVF were Gardnerella . Gardnerella was found to be associated with increased levels of succinic acid, thereby highlighting distinct metabolic profiles. These findings suggest that the development of cervical lesions resulting from persistent HR-HPV infection is associated with significant alterations in systemic metabolism and shifts in the cervicovaginal microbiota, providing valuable insights into the metabolic and microbiota changes linked to disease severity.