Vaginal microbiome and human papillomavirus infection: mechanisms of interaction, diagnosis and therapeutic perspectives
Bebneva T.N., Minaeva A.V., Akhmatova A.N., Ramazanova F.U.
Background: Persistence of high-risk human papillomavirus (HPV) types is a necessary condition for the development of cervical neoplasia; however, most HPV infections are cleared spontaneously. The vaginal microbiota is considered a key modifiable factor determining the outcomes of HPV infection. Lactobacillus-dominant communities are associated with higher rates of viral clearance, whereas dysbiotic conditions contribute to the persistence and progression of cervical lesions.
Materials and methods: This paper is a narrative literature review based on a targeted search of publications in the PubMed, Scopus, Web of Science, and eLIBRARY.RU databases from 2015 to 2025 using the following keywords «vaginal microbiome», «HPV», «cervical intraepithelial neoplasia», «Lactobacillus», «bacterial vaginosis», «HPV genotyping». The review included original studies, systematic reviews, meta-analyses and clinical guidelines focusing on the relationship between the vaginal microbiome and HPV infection. When selecting sources, priority was given to clinical studies, high-quality reviews and current guidelines.
Results: The state of the vaginal microbiome was found to be associated with the outcomes of HPV infection and the progression of cervical intraepithelial lesions. Lactobacillus crispatus-dominant communities (CST I) are associated with a 3.5-fold higher probability of spontaneous regression of CIN2 compared with dysbiotic states (CST IV). Modern molecular methods make it possible to simultaneously assess the composition of the vaginal microbiota, the predominant species of lactobacilli (typing of L. crispatus, L. jensenii/L. mulieris, L. gasseri/L. paragasseri, L. iners) and extended HPV genotyping with individual identification of types 16, 18, 45 and pooled detection of types 31/33/35/39/51/52/56/58/59/66/68, which may broaden the possibilities for risk stratification.
Conclusion: The vaginal microbiome should be regarded as a promising risk biomarker and a potential therapeutic target in HPV-associated diseases. The FEMOFLOR II diagnostic system provides an optimal tool for personalized risk stratification, combining an assessment of the microbiota with Lactobacillus typing and extended HPV genotyping in accordance with current clinical guidelines.
Authors’ contributions: Bebneva T.N. – developing the concept and design of the review; Minaeva A.V. – collecting and processing the material; Ramazanova F.U. – performing the literature analysis; Minaeva A.V., Akhmatova A.N. – writing the text; Bebneva T.N. – editing the article. All the authors participated in the approval of the final version of the article.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was conducted without sponsorship.
Disclosing AI use: In preparing this article, the virtual AI assistant Alice (Yandex’s Alice AI family of generative models) was used exclusively to translate the abstract. The generated text was checked, edited and approved by the authors. The authors bear full responsibility for the content of the manuscript.
For citation: Bebneva T.N., Minaeva A.V., Akhmatova A.N., Ramazanova F.U. Vaginal microbiome and human papillomavirus infection: mechanisms of interaction, diagnosis and therapeutic perspectives.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (4): 182-190 (in Russian)
https://dx.doi.org/10.18565/aig.2026.104
Keywords
References
- Leon-Gomez P., Romero V.I. Human papillomavirus, vaginal microbiota and metagenomics: the interplay between development and progression of cervical cancer. Front. Microbiol. 2025; 15: 1515258. https://dx.doi.org/10.3389/fmicb.2024.1515258
- Kyrgiou M., Mitra A., Moscicki A.B. Does the vaginal microbiota play a role in the development of cervical cancer? Transl. Res. 2017; 179: 168-82. https://dx.doi.org/10.1016/j.trsl.2016.07.004
- Бебнева Т.Н., Дикке Г.Б. Рецидивирующие нарушения биоценоза влагалища, ассоциированные с бактериальным вагинозом, у беременных женщин с ВПЧ-инфекцией. Акушерство и гинекология. 2018; 9: 55-60. [Bebneva T.N., Dikke G.B. Recurrent vaginal biocenotic disorders associated with bacterial vaginosis in pregnant women with HPV infection. Obstetrics and Gynecology. 2018; (9): 55-60. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.9.55-60
- Бебнева Т.Н., Дикке Г.Б. Интраэпителиальные поражения шейки матки низкой степени риска у беременных женщин с ВПЧ и нарушениями биоценоза влагалища. Акушерство и гинекология. 2018; 11: 152-8. [Bebneva T.N., Dikke G.B. Low–grade intraepithelial cervical lesions in pregnant women with HPV and vaginal biocenotic disorders. Obstetrics and Gynecology. 2018; (11): 152-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.11.152-158
- Massad L.S., Clarke M.A., Perkins R.B., Garcia F., Chelmow D., Cheung L.C. et al. Applying results of extended genotyping to management of positive cervicovaginal human papillomavirus test results: enduring guidelines. J. Low Genit. Tract. Dis. 2025; 29(2): 134-43. https://dx.doi.org/10.1097/LGT.0000000000000865
- France M.T., Ma B., Gajer P., Brown S., Humphrys M.S., Holm J.B. et al. VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition. Microbiome. 2020; 8(1): 166. https://dx.doi.org/10.1186/s40168-020-00934-6
- Amabebe E., Anumba D.O.C. The vaginal microenvironment: the physiologic role of Lactobacilli. Front. Med. (Lausanne). 2018; 5: 181. https://dx.doi.org/10.3389/fmed.2018.00181
- Mitra A., MacIntyre D.A., Ntritsos G., Smith A., Tsilidis K.K., Marchesi J.R. et al. The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat. Commun. 2020; 11(1): 1999. https://dx.doi.org/10.1038/s41467-020-15856-y
- Novak J., Belleti R., da Silva Pinto G.V., do Nascimento Bolpetti A., da Silva M.G., Marconi C. Cervicovaginal Gardnerella sialidase-encoding gene in persistent human papillomavirus infection. Sci. Rep. 2023; 13(1): 14266. https://dx.doi.org/10.1038/s41598-023-41469-8
- Jimenez N.R., Mancilla V., Łaniewski P., Herbst-Kralovetz M.M. Immunometabolic contributions of Atopobiaceae family members in human papillomavirus infection, cervical dysplasia, and cancer. J. Infect. Dis. 2025; 232(4): 767-78. https://dx.doi.org/10.1093/infdis/jiae533
- Mitra A., MacIntyre D.A., Lee Y.S., Smith A., Marchesi J.R., Lehne B. et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci. Rep. 2015; 5: 16865. https://dx.doi.org/10.1038/srep16865
- Li X., Xiang F., Liu T., Chen Z., Zhang M., Li J. et al. Leveraging existing 16S rRNA gene surveys to decipher microbial signatures and dysbiosis in cervical carcinogenesis. Sci. Rep. 2024; 14(1): 11532. https://dx.doi.org/10.1038/s41598-024-62531-z
- Lee J.E., Lee S., Lee H., Song Y.M., Lee K., Han M.J. et al. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort. PLoS One. 2013; 8(5): e63514. https://dx.doi.org/10.1371/journal.pone.0063514
- Zhu H., Shen Z., Luo H., Zhang W., Zhu X. Chlamydia trachomatis infection-associated risk of cervical cancer: a meta-analysis. Medicine (Baltimore). 2016; 95(13): e3077. https://dx.doi.org/10.1097/MD.0000000000003077
- Ye H., Song T., Zeng X., Li L., Hou M., Xi M. Association between genital mycoplasmas infection and human papillomavirus infection, abnormal cervical cytopathology, and cervical cancer: a systematic review and meta-analysis. Arch. Gynecol. Obstet. 2018; 297(6): 1377-87. https://dx.doi.org/10.1007/s00404-018-4733-5
- Klein C., Samwel K., Kahesa C., Mwaiselage J., West J.T., Wood C. et al. Mycoplasma co-infection is associated with cervical cancer risk. Cancers (Basel). 2020; 12(5): 1093. https://dx.doi.org/10.3390/cancers12051093
- Gaydos C.A., Beqaj S., Schwebke J.R., Lebed J., Smith B., Davis T.E. et al. Clinical validation of a test for the diagnosis of vaginitis. Obstet. Gynecol. 2017; 130(1): 181-9. https://dx.doi.org/10.1097/AOG.0000000000002090
- Инструкция по применению набора реагентов для количественной оценки состава микробиоты, качественного и количественного определения ДНК основных патогенных микроорганизмов в репродуктивном тракте женщин методом ПЦР в режиме реального времени ФЕМОФЛОР II. М.: ДНК-Технологии; 2025. Регистрационное удостоверение № РЗН 2025/24831 от 14.02.2025. [Instructions for use of the set of reagents for quantitative assessment of the composition of the microbiota, qualitative and quantitative determination of the DNA of the main pathogenic microorganisms in the reproductive tract of women by real-time PCR using FEMOFLOR II. Moscow: DNA Technologies; 2025. Registration Certificate No. RZN 2025/24831 dated February 14, 2025 (in Russian)].
- Borgogna J.C., Shardell M.D., Santori E.K., Nelson T.M., Rath J.M., Glover E.D. et al. The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis. BJOG. 2020; 127(2): 182-92. https://dx.doi.org/10.1111/1471-0528.15981
- XiaoNan L, MeiHan C, Dan H. Vaginal Microenvironment-Driven neural network model for predicting multiple HPV co-infections: a machine learning clinical decision framework. BMC Womens Health. 2025; 25(1): 489. https://dx.doi.org/10.1186/s12905-025-03957-z
- Susetiati D.A., Pudjiati S.R., Wirohadidjojo Y.W., Chandra L.A. Effectiveness of Lactobacillus therapy in women with cervical human papillomavirus infection: a systematic review and meta-analysis. J. Int. Med. Res. 2025; 53(8): 3000605251363006. https://dx.doi.org/10.1177/03000605251363006
- Dellino M., Cascardi E., Laganà A.S., Di Vagno G., Malvasi A., Zaccaro R. et al. Lactobacillus crispatus M247 oral administration: is it really an effective strategy in the management of papillomavirus-infected women? Infect. Agent. Cancer. 2022; 17(1): 53. https://dx.doi.org/10.1186/s13027-022-00465-9
- Di Pierro F., Sampugnaro E.G., Lomeo G.E., Guarneri M.F., Cusenza S., Pivetti A. et al. Effect of orally administered L. crispatus M247 in favoring HR-HPV clearance and CST shift: results from a randomized, multi-center, placebo-controlled trial. Sci. Rep. 2025; 15(1): 36881. https://dx.doi.org/10.1038/s41598-025-20838-5
- Liu Y., Zhao X., Wu F., Chen J., Luo J., Wu C. et al. Effectiveness of vaginal probiotics Lactobacillus crispatus chen-01 in women with high-risk HPV infection: a prospective controlled pilot study. Aging (Albany NY). 2024; 16(14): 11446-59. https://dx.doi.org/10.18632/aging.206032
- Palma E., Recine N., Domenici L., Giorgini M., Pierangeli A., Panici P.B. Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection. BMC Infect. Dis. 2018; 18(1): 13. https://dx.doi.org/10.1186/s12879-017-2938-z
- Verhoeven V., Renard N., Makar A., Van Royen P., Bogers J.P., Lardon F. et al. Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study. Eur J. Cancer Prev. 2013; 22(1): 46-51. https://dx.doi.org/10.1097/CEJ.0b013e328355ed23
- Lev-Sagie A., Goldman-Wohl D., Cohen Y., Dori-Bachash M., Leshem A. et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat. Med. 2019; 25(10): 1500-04. https://dx.doi.org/10.1038/s41591-019-0600-6
- Столярова У.В., Хворостухина Н.Ф., Новичков Д.А., Суворова Г.С., Однокозова О.С. Возможности воздействия на эпителизацию шейки матки при деструктивных методах терапии у пациенток с цервикальной интраэпителиальной неоплазией, рецидивирующим бактериальным вагинозом и папилломавирусной инфекцией. Акушерство и гинекология. 2025; 10: 136-42. [Stolyarova U.V., Khvorostukhina N.F., Novichkov D.A., Suvorova G.S., Odnokozova O.S. The impact on cervical epithelialization in destructive treatment in patients with cervical intraepithelial neoplasia, recurrent bacterial vaginosis and papillomavirus infection. Obstetrics and Gynecology. 2025; (10): 136-42 (in Russian)]. https://dx.doi.org/10.18565/aig.2025.264
- Рахматулина М.Р. Эффективность комплексной терапии бактериального вагиноза, ассоциированного с папилломавирусной инфекцией, с применением активированной глицирризиновой кислоты. Акушерство и гинекология. 2025; 10: 149-56. [Rakhmatulina M.R. The effectiveness of complex therapy with activated glycyrrhizic acid in patients with bacterial vaginosis associated with papillomavirus infection. Obstetrics and Gynecology. 2025; (10): 149-56 (in Russian)]. https://dx.doi.org/10.18565/aig.2025.294
Received 27.03.2026
Accepted 23.04.2026
About the Authors
Tamara N. Bebneva, Dr. Med. Sci., Associate Professor at the Department of Obstetrics, Gynecology and Reproductive Medicine, Faculty of Continuing Medical Education, Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, bebn@mail.ru,https://orcid.org/0000-0003-1095-2008
Anastasia V. Minaeva, Teaching Assistant at the Department of Obstetrics and Gynecology with Course of Perinatology, Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, +7(915)101-86-39, minaeva-av@rudn.ru, https://orcid.org/0000-0002-8066-0839
Anastasiya N. Akhmatova, PhD, Associate Professor at the Department of Obstetrics and Gynecology with Course of Perinatology, Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, +7(922)733-23-33, achmatova02@mail.ru,
https://orcid.org/0000-0001-8653-9389
Fatima U. Ramazanova, PhD, Teaching Assistant at the Department of Obstetrics and Gynecology with the Course of Perinatology, Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba, 117198, Russia, Moscow, Miklukho-Maklaya str., 6, +7(925)417-98-23, fatimasiren@yandex.ru,
https://orcid.org/0000-0002-4574-3874
Corresponding author: Fatima U. Ramazanova, fatimasiren@yandex.ru



