Microbial diversity in the vaginal microbiota in women with high-grade squamous intraepithelial lesion

Aim. To study the types of vaginal microbial communities in women with high-grade squamous intraepithelial lesion (HSIL) and those negative for intraepithelial lesion or malig­nancy (NILM).

Materials and Methods. Between 2021 and 2023, we conducted an analysis of vaginal microbial com­munity types among 70 women of reproductive age infected with high-risk oncogenic HPV: those with HSIL verified by cytological examination (n = 40) and those without precancerous cervical lesions (i.e., NILM, n = 30). Identification of microorganisms in the cervical mucus was identified by mass spectrometry.

Results. The frequency of normal microbiota detected by the microscopic examination was 5.3-fold lower, whilst Streptococcus spp. was detected 3-fold times higher in women with HSIL compared to the NILM group (p = 0.023). Among patients with HSIL, community state type (CST) IV was the most frequent (75%), and CST IV-C1 subtype (with Streptococcus spp. as a prevailing genus) was found in 25% of cases (p = 0.132). In patients with NILM, CST IV was also the predominant type (60%) but CST IV-C2 (with En­terococcus spp. as a prevailing genus) was most frequent subtype (23.3%, p = 0.087). The prevalence of HPV type 16 and grade 2 abnormal colposcopy findings were 3.9-fold (p = 0.008) and 3.5-fold (p = 0.040) higher in women with HSIL than in NILM (p = 0.008).

Conclusion. The predominant type among vaginal microbial communities in women with HSIL and NILM was CST IV, with C1 and C2 subtypes pre­vailing respectively in HSIL and NILM.

1. Kaprin AD, Starinskii VV, Shakhzadov AO. Zlokachestvennye novoobrazovaniya v Rossii v 2021 godu (zabolevaemost' i smertnost'). Moscow : MNIOI im PA Gertsena – filial FGBU ≪NMITs radiologii≫ Minzdrava Rossii; 2022. (In Russian).

2. Fernandes A, Viveros-Carreño D, Hoegl J, Ávila M, Pareja R. Human papillomavirus-independent cervical cancer. Int J Gynecol Cancer. 2022;32(1):1-7. https://doi.org/10.1136/ijgc-2021-003014

3. Kira EF, Yatsyshina DV, D'yakonov SA. Mikrobnye tainy. StatusPraesens. Ginekologiya, akusherstvo, besplodnyi brak. 2020;4(69):70-75. (In Russian).

4. Sharifian K, Shoja Z, Jalilvand S. The interplay between human papillomavirus and vaginal microbiota in cervical cancer development. Virol J. 2023;20(1):73. 1 https://doi.org/0.1186/s12985-023-02037-8

5. Radzinskogo VE, Savichevoi AM, editors. Biotsenoz vlagalishcha. Norma. Narushenie. Vosstanovlenie. Moscow : StatusPraesens; 2023. (In Russian). https://doi.org/10.29039/978-5-907218-72-7

6. Audirac-Chalifour A, Torres-Poveda K, Bahena-Román M, TéllezSosa J, Martínez-Barnetche J, Cortina-Ceballos B, López-Estrada G, Delgado-Romero K, Burguete-García AI, Cantú D, García-Carrancá A, Madrid-Marina V. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study. PLoS One. 2016;11(4):e0153274. https://doi.org/10.1371/journal.pone.0153274

7. Brotman RM, Shardell MD, Gajer P, Tracy JK, Zenilman JM, Ravel J, Gravitt PE. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J Infect Dis. 2014;210(11):1723-1733. https://doi.org/10.1093/infdis/jiu330

8. Di Paola M, Sani C, Clemente AM, Iossa A, Perissi E, Castronovo G, Tanturli M, Rivero D, Cozzolino F, Cavalieri D, Carozzi F, De Filippo C, Torcia MG. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection. Sci Rep. 2017;7(1):10200. https://doi.org/10.1038/s41598-017-09842-

9. Budilovskaya OV, Shipitsyna E.V., Gerasimova E.N., Safronova M.M., Savicheva A.M. Species diversity of vaginal lactobacilli in norm and in dysbiotic states. Journal of obstetrics and womans diseases. 2017;66(2):24-32. (In Russian). https://doi.org/10.17816/JOWD66224-32

10. France MT, Ma B, Gajer P, Brown S, Humphrys MS, Holm JB, Waetjen LE, Brotman RM, Ravel J. VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition. Microbiome. 2020;8(1):166. https://doi.org/10.1186/s40168-020-00934-6

11. Chao X, Wang L, Wang S, Lang J, Tan X, Fan Q, Shi H. Research of the Potential Vaginal Microbiome Biomarkers for High-Grade Squamous Intraepithelial Lesion. Front Med (Lausanne). 2021;8:565001. https://doi.org/10.3389/fmed.2021.565001

12. Kang GU, Jung DR, Lee YH, Jeon SY, Han HS, Chong GO, Shin JH. Potential Association between Vaginal Microbiota and Cervical Carcinogenesis in Korean Women: A Cohort Study. Microorganisms. 2021;9(2):294. https://doi.org/10.3390/microorganisms9020294

13. Wu M, Gao J, Wu Y, Li Y, Chen Y, Zhao F, Li C, Ying C.Characterization of vaginal microbiota in Chinese women with cervical squamous intraepithelial neoplasia. Int J Gynecol Cancer. 2020;30(10):1500-1504. https://doi.org/10.1136/ijgc-2020-001341

14. Chen Y, Qiu X, Wang W, Li D, Wu A, Hong Z, Di W, Qiu L. Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort. BMC Infect Dis. 2020;20(1):629. https://doi.org/10.1186/s12879-020-05324-9

15. Williamson AL. Recent Developments in Human Papillomavirus (HPV) Vaccinology. Viruses. 2023;15(7):1440. https://doi.org/10.3390/v15071440

16. Brotherton JM, Tabrizi SN, Garland SM. Does HPV type 16 or 18 prevalence in cervical intraepithelial neoplasia grade 3 lesions vary by age? An important issue for postvaccination surveillance. Future Microbiol. 2012;7(2):193-199. https://doi.org/10.2217/fmb.11.161

17. Yu H, Ma L, Bian M, Li Q, Liang H. Association of abnormal vaginal microflora and HPV infection in cervical precancerous lesions: a retrospective study. J Infect Dev Ctries. 2022;16(6):1089-1095. https:// doi.org/10.3855/jidc.15961

18. Pretorius RG, Belinson JL. Colposcopy. Minerva Ginecol. 2012;64(2):173-180.