Vaginal microbiota profile in human papillomavirus-associated cervical disease and its diagnostic value for cervical intraepithelial neoplasia II+
Kepsha M.A., Mezhevitinova E.A., Timofeeva A.V., Fedorov I.S., Donnikov A.E.
Objective. To characterize the vaginal microbiota in patients with different clinical and morphological forms of human papillomavirus (HPV)-associated cervical disease and assess its relationship with the presence of high-grade cervical intraepithelial lesions and cervical cancer (CIN II+).
Materials and methods. This analytical study included 190 women who were examined at the V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation. The following groups were defined: NILM/HPV+ (n=50), LSIL (n=52), HSIL (n=52), and cervical cancer (n=36). Quantitative and qualitative assessments of the vaginal microbiota were performed using real-time PCR (Femoflor-16 assay). HPV genotyping and viral load quantification were performed.
Results. Increasing severity of HPV-associated cervical disease was accompanied by a marked reduction in the relative abundance of Lactobacillus spp. and an increase in the proportion of anaerobic microbial communities. The most pronounced dysbiotic changes were observed in patients with cervical cancer (p<0.001). Stratification into CIN I- (NILM/HPV+, LSIL) and CIN II+ (HSIL, cervical cancer) groups revealed statistically significant differences in HPV genotype distribution and the qualitative and quantitative composition of the microbial consortia. Six logistic regression models were developed for the first time, each incorporating three or four independent variables and demonstrating high sensitivity (80–86%) and specificity (75–80%) in identifying CIN II+. These models included various combinations of quantitative characteristics of HPV types 16 and 33 and selected opportunistic pathogens. All models incorporated a novel index proposed by the authors: the ratio of the total quantities of "possibly carcinogenic" HPV types to "carcinogenic" HPV types, which increased model sensitivity by 4–18%.
Conclusion. Distinct vaginal microbiota profiles are associated with severe HPV-related cervical disease. A comprehensive assessment of the vaginal microbiome in conjunction with HPV status may serve as an additional tool for differentiating clinically significant cervical lesions.
Authors' contributions. Kepsha M.A. – data collection, literature search and analysis, drafting of the manuscript; Mezhevitinova E.A. – data collection, editing of the manuscript, approval of the final version of the manuscript; Timofeeva A.V. – drafting of the manuscript, approval of the final version of the manuscript; Fedorov I.S. – statistical analysis; Donnikov A.E. – obtaining experimental data.
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. There was no funding for this study.
Ethical Approval. The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication. All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement. The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Kepsha M.A., Mezhevitinova E.A., Timofeeva A.V., Fedorov I.S., Donnikov A.E. Vaginal microbiota profile in human papillomavirus-associated cervical disease and its diagnostic value for cervical intraepithelial neoplasia II+.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (5): 108-120 (in Russian)
https://dx.doi.org/10.18565/aig.2026.71
Keywords
human papillomavirus (HPV)
vaginal microbiota
cervical intraepithelial neoplasia
CIN I-
CIN II+
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Received 27.02.2026
Accepted 10.04.2026
About the Authors
Maria A. Kepsha, Junior Researcher at the Scientific and Outpatient Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Ac. Oparin str., Moscow, 117997, Russia, m_kepsha@oparina4.ru, https://orcid.org/0000-0002-4201-1360Elena A. Mezhevitinova, Dr. Med. Sci., Leading Researcher at the Scientific and Outpatient Department, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Ac. Oparin str., Moscow, 117997, Russia, mejevitinova@mail.ru, https://orcid.org/0000-0003-2977-9065
Angelica V. Timofeeva, PhD (Bio), Head of the Laboratory of Applied Transcriptomics of the Department of Systems Biology in Reproduction, Institute of Translational Medicine, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Ac. Oparin str., Moscow, 117997, Russia, avtimofeeva28@gmail.com, https://orcid.org/0000-0003-2324-9653
Ivan S. Fedorov, Researcher at the Laboratory of Transcriptomic, Department of Systems Biology in Reproduction, Institute of Translational Medicine, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Ac. Oparin str., Moscow, 117997, Russia, is_fedorov@oparina4.ru, https://orcid.org/0000-0002-2104-5887
Andrey E. Donnikov, PhD, Head of the Laboratory of Molecular Genetic Methods, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Ac. Oparin str., Moscow, 117997, Russia, donnikov@dna-technology.ru, https://orcid.org/0000-0003-3504-2406
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