Cervical microbiota changes regarding hrHPV-VL. Changes in cervical microbiota of women with different high risk human papillomavirus loads

The cervical microbiota is essential in female sexual health. Dysbiosis states favor the colonization of pathogens, including high-risk papillomavirus (hrHPV); however, the relation between hrHPV load and the cervical microbiota composition has not been explored. This study aimed to evaluate variation in the composition of the bacterial communities according to the hrHPV load in a longitudinal approach. We collected two samples per woman with a difference of 12 months ± 1-months between them and performed a follow-up on 66 of these women (132 samples). Viral Load (VL) of the hrHPV in each sample was estimated by quantitative PCR (qPCR). The microbiota composition was described through amplicon-based sequencing of the hypervariable region V4 of the 16S-rRNA gene, using the platform Illumina Novaseq PE250. The diversity analyses revealed changes regarding the hrHPV copy number, where women with low VL (>100 hrHPV copies) presented high diversity. The Community State Type (CST) IV was the most common. However, in women with high VL, a lower association with Lactobacillus depletion was found. L. gallinarum y L. iners were the most abundan species in women with high VL, whereas women with low VL had a 6.06 greater probability of having a Lactobacillus dominance. We identified conspicuous differences in the abundance of 78 bacterial genera between women with low and high VL, where 26 were depleted (e.g., Gardnerella and Megasphaera) and 52 increased (e.g., Mycoplasma and Spirochaeta). A multilevel mixed-effects linear regression showed changes in the diversity due to the interaction between the measurement time and the VL, with a decrease in diversity in the second follow-up in women with low VL (Coeff= 0.47), whereas the women with medium VL displayed an increase in diversity (Coeff= 0.58). Here, we report for the first time that the cervical microbiota is influenced by the number of copies of hrHPV, where a decrease in the abundance of Lactobacillus, greater diversity, and enrichment of bacterial taxa is relevant in women with low VL.