AUTHOR=López-Filloy Mariana , Cortez Flor J. , Gheit Tarik , Cruz y Cruz Omar , Cruz-Talonia Fernando , Chávez-Torres Monserrat , Arteaga-Gómez Cristina , Mancilla-Herrera Ismael , Montesinos Juan J. , Cortés-Morales Víctor Adrián , Aguilar Cecilia , Tommasino Massimo , Pinto-Cardoso Sandra , Rocha-Zavaleta Leticia 

TITLE=Altered Vaginal Microbiota Composition Correlates With Human Papillomavirus and Mucosal Immune Responses in Women With Symptomatic Cervical Ectopy

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.884272

DOI=10.3389/fcimb.2022.884272

ISSN=2235-2988

ABSTRACT=Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay, evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16, HPV31 and HPV18. IL-21 and MIG were significantly upregulated in women with cervical ectopy and HPV infection (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p<0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1β, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Our results suggest that the dynamic interplay between the vaginal microbiota and HPV in women with symptomatic cervical ectopy might not only increase their vulnerability to STDs, but also induce chronic inflammation and epithelial damage creating a potentially pro-carcinogenic microenvironment if left untreated and if HPV persists.