The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis

Objective: Characterise the vaginal metabolome of cervical HPV-infected and uninfected women.

Design: Cross-sectional.

Setting: The Center for Health Behavior Research at the University of Maryland School of Public Health.

Sample: Thirty-nine participants, 13 categorised as HPV-negative and 26 as HPV-positive (any genotype; HPV⁺ ), 14 of whom were positive with at least one high-risk HPV strain (hrHPV).

Method: Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing, metabolites by both gas and liquid chromatography mass spectrometry, and 37 types of HPV DNA.

Main outcome measures: Metabolite abundances.

Results: Vaginal microbiota clustered into Community State Type (CST) I (Lactobacillus crispatus-dominated), CST III (Lactobacillus iners-dominated), and CST IV (low-Lactobacillus, 'molecular-BV'). HPV⁺ women had higher biogenic amine and phospholipid concentrations compared with HPV^- women after adjustment for CST and cigarette smoking. Metabolomic profiles of HPV⁺ and HPV^- women differed in strata of CST. In CST III, there were higher concentrations of biogenic amines and glycogen-related metabolites in HPV⁺ women than in HPV^- women. In CST IV, there were lower concentrations of glutathione, glycogen, and phospholipid-related metabolites in HPV⁺ participants than in HPV^- participants. Across all CSTs, women with hrHPV strains had lower concentrations of amino acids, lipids, and peptides compared with women who had only low-risk HPV (lrHPV).

Conclusions: The vaginal metabolome of HPV⁺ women differed from HPV^- women in terms of several metabolites, including biogenic amines, glutathione, and lipid-related metabolites. If the temporal relation between increased levels of reduced glutathione and oxidised glutathione and HPV incidence/persistence is confirmed in future studies, anti-oxidant therapies may be considered as a non-surgical HPV control intervention.

Tweetable abstract: Metabolomics study: Vaginal microenvironment of HPV⁺ women may be informative for non-surgical interventions.