Vaginal microbiome and HPV persistence: the role of bacterial vaginosis in cervical carcinogenesis

Iurova M.V., Abakarova P.R., Mezhevitinova E.A., Aksenova A.V.

1) National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia; 2) I.M. Sechenov First Moscow State Medical University (Sechenov University), Department of Obstetrics, Gynecology, Perinatology and Reproductive Medicine, Institute of Postgraduate Education, Moscow, Russia; 3) I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

Human papillomavirus (HPV) causes one of the most common sexually transmitted infections, especially in women of reproductive age. Dysbiotic changes in the vaginal microbiota are characterized by a decrease in the number of Lactobacillus bacteria with a predominance of opportunists in the form of increased representation of anaerobic bacteria and fungi. Microbial communities affect processes such as inflammation, immune evasion, and metabolic reprogramming. The microbiota of HPV-positive women is cha-racterized by a higher diversity of representatives (including Dialister, Prevotella, Fannyhessea vaginae, Gardnerella, Megasphaera, Peptoniphilus, Sneathia, Eggerthella, Aerococcus, Finegoldia, Mobiluncus) and a decrease in the relative abundance of Lactobacillus spp., as well as an increased pH of the vaginal environment. Anaerobic dysbiosis (bacterial vaginosis), as well as aerobic and mixed dysbiosis predispose to long-term persistence of HPV infection. Chronic inflammation associated with the action of cytokines (interleukin-6 – IL-6, IL-8, IL-10, IL-1β and tumor necrosis factor α) and the involvement of immune cells is accompanied by changes in the metabolic profile of the cervical microenvironment. This leads to disruption of local immunocompetent barriers of the mucous membrane and, in some cases, is accompanied by stable maintenance of a proinflammatory environment, which contributes to the creation of conditions for persistence and integration of the virus into the genome – key stages of cervical carcinogenesis. This article shows that dysbiosis of the cervicovaginal microbiome is a cofactor for the prognostically unfavorable course of HPV infection, as well as associated cervical dysplasia and subsequent malignancy. Omics technologies, including metagenomics, metabolomics and proteomics, offer comprehensive tools for studying the relationship between the cervical-vaginal microbiota of the cervix and malignancy, as they detail the characteristics of microbial communities, their functional roles, revealing the metabolic changes caused by the microbiota and involved in carcinogenesis. Together, this provides markers for early detection, prognosis, and can also be used for preventive and therapeutic purposes. The importance of the stage of timely and complete correction of dysbiosis from the standpoint of cervical cancer prevention is shown.

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About the Authors

M.V. Iurova, Cand. Sci. (Med.), Obstetrician-Gynecologist, Oncologist, Senior Researcher, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov; Teaching Assistant at the Department of Obstetrics, Gynecology, Perinatology and Reproductology, Institute of Postgraduate Education, I.M. Sechenov First Moscow State Medical University, Moscow; m_yurova@oparina4.ru, ORCID: https://orcid.org/0000-0002-0179-7635117997 (corresponding author)
P.R. Abakarova, Cand. Sci. (Med.), Obstetrician-Gynecologist, Senior Researcher, Research and Outpatient Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia; p_abakarova@oparina4.ru, ORCID: https://orcid.org/0000-0002-8243-5272
E.A. Mezhevitinova, Dr. Sci. (Med.), Obstetrician-Gynecologist, Leading Researcher, Research and Outpatient Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov, Moscow, Russia; e_mezhevitinova@oparina4.ru, ORCID: https://orcid.org/0000-0003-2977-9065
A.V. Aksenova, Student, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow; axenova175@mail.ru, ORCID:
https://orcid.org/0009-0003-9962-6854

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