Metabolomic and Microbiota Profiles in Cervicovaginal Lavage Fluid of women with High- Risk Human Papillomavirus Infection

Abstract 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 16S 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 (P < 0.05) 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 Lactobacillus and Gardnerella. There was a significant negative correlation between succinic acid and Gardnerella. These findings suggest significant systemic metabolic changes in HR-HPV infection as it progresses to cervical lesions, providing valuable insights into the associated metabolic alterations and their association with disease severity.