Changes in the Cervical Microbiota of Women with Different High-Risk Human Papillomavirus Loads

The cervical microbiota is essential in female sexual health, and its altered states seem to have a central role in the dynamic of high-risk papillomavirus (hrHPV) infections. This study aimed to evaluate the variation in bacterial communities’ compositions according to hrHPV. We collected two samples per woman, with a difference of 12 ± 1 months between them, and performed a follow-up on 66 of these women. The viral load (VL) of the hrHPV was estimated by quantitative PCR (qPCR), then it was normalized (using the <i>HMBS</i> gene as reference) and transformed to the Log₁₀ scale to facilitate the interpretation. The VL was categorized as Negative, without hrHPV copies; Low, less than 10⁰ hrHPV copies; Medium, between 10⁰ to 10² hrHPV copies; and High, >10² hrHPV copies. The microbiota composition was described through the Illumina Novaseq PE250 platform. The diversity analyses revealed changes regarding the hrHPV VL, 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 <i>Lactobacillus</i> depletion was found. <i>Lactobacillus gallinarum</i> and <i>L. iners</i> were the most abundant species in women with high VL, whereas women with low VL had a 6.06 greater probability of exhibiting <i>Lactobacillus</i> 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., <i>Gardnerella</i>) and 52 increased (e.g., <i>Mycoplasma</i>). 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 <i>Lactobacillus</i>, greater diversity, and enrichment of bacterial taxa is relevant in women with low VL.