Lactobacillus-rich cervicovaginal microbiome associated with lower BV, HPV, and cytology outcomes in women

Abstract

The cervicovaginal microbiome modulates susceptibility to bacterial vaginosis (BV), high-risk human papillomavirus (hrHPV) infection, and epithelial cell abnormalities that precede cervical cancer. We retrospectively analyzed 15 607 qPCR-profiled cervicovaginal specimens from U.S. women (ages 14–95; 32 states) and integrated microbiome abundances, hrHPV genotyping, Pap-cytology, and demographics. BV was present in 53% and hrHPV in 11% of samples. Lactobacillus crispatus, L. gasseri, and L. jensenii were enriched in BV-negative and cytologically normal (NILM) samples, whereas L. iners and BV-associated anaerobes co-occurred with hrHPV and abnormal cytology. Machine-learning models confirmed age, hrHPV status, and L. crispatus abundance as the strongest multivariate predictors of BV and cytological outcomes (BV AUROC ≈0.97). Interaction analyses revealed synergistic associations between specific hrHPV genotypes and Gardnerella/Fannyhessea that further increased cytological risk. These findings underscore the clinical value of microbiome profiling and support probiotic strategies that promote protective Lactobacillus communities to reduce BV and hrHPV-related cervical pathology.