Inflammatory cytokines and a diverse cervicovaginal microbiome are associated with cervical disease in Hispanics living in Puerto Rico

Abstract

AbstractCervical cancer (CC) is women’s fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human Papillomaviruses infections, there may be other biological causes promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression. There is a lack of studies examining the part played by microbial populations in the development of precancerous lesions into cancer in Hispanic women. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical neoplasia and HPV infection. Cervical samples collected from 91 participants coming to clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology. Cytokines were grouped as inflammatory (IL-1β, TNFα, IFNγ, IL-6), anti-inflammatory (IL-4, IL-10, TGFβ1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine’s concentration. We found significant differences in the diversity and composition of the microbiota according to HPV risk, cervical disease, and cytokine abundance. The most dominant community state type (CST) was CST IV with ∼ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory cytokines was associated with a decrease inL. crispatus. In contrast, dysbiosis-associated bacteria such asGardnerella,Prevotella,Atopobiumconcomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in PR is characteristically diverse, regardless of HPV status and that dysbiosis associated with a decrease inLactobacillusmarks inflammatory processes. Therefore, the joint host-microbe interaction analyses via cytokine signaling and microbiota in precancerous lesions is confirmed to have great translational potential.