Human papillomavirus: genetic diversity, vaginal microbiota, and local immunity in cervical intraepithelial neoplasia

Objective. To assess the contribution of HPV and to examine the state of vaginal microecology in women with HPV-induced cervical intraepithelial neoplasia (using the Gomel region as an example).

Materials and methods. The study was carried out in the period from 2018 to 2023 and included 11,382 women from the Gomel region. A study of cervical canal scrapings was performed using the cytological method. The molecular genetic testing of these samples for the presence of DNA of the human papillomavirus (HPV) of high carcinogenic risk (hr) was carried out using the Abbott Real Time hrHPV reagent kit (USA). The genotyping of positive samples was performed using the AmpliSens hrHPV genotype-FL kit (RF). A microbiological study of vaginal discharge from HPV-negative women (n = 78) was conducted with an assessment of the state of the vaginal microbiocenosis and an assessment of the functions of lactobacilli. An immunological study of cervicovaginal secretion included the determination of interleukins: IL-1β, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha and secretory immunoglobulin A.

Results. The prevalence of hrHPV in women in the Gomel region was 9.0%. hrHPV was detected with the highest frequency in the 18–24 age group — 19% (95% CI 17–21.1). It was found that during the study period, 16, 18, 51, 56 and 31 were found with the highest frequency. Genotype 16 (73.8%) was detected significantly more often in high-grade squamous intraepithelial lesions, genotypes 45 (14.9%) and 58 (11.9%) in low-grade squamous intraepithelial lesions, and genotype 33 (14.8%) in atypical squamous cells of undetermined significance. Dysbiosis was detected significantly more often with HPV-negative cervical dysplasia (87.2%), and severe dysbiosis in this group was noted with a high frequency — 66.7%. The antagonistic activity of lactobacilli in the group with cervical dysplasia was 2 times lower in relation to all test strains compared to the group with normocytogram. In the group with dysplasia, the ability of lactobacilli to produce hydrogen peroxide was absent in 92.3% of cases and the ability to form biofilm was significantly reduced. According to the results of the analysis, the following may be considered unfavorable factors in HPV-negative dysplasia: vaginal dysbiosis, increased pH of vaginal discharge, increased IL-6, decreased levels of secretory immunoglobulin A.

Conclusion. Thus, both HPV and factors characterizing the vaginal microecology contribute to the development of cervical dysplasia. The presented results are not only of practical but also of fundamental importance, as they expand our understanding of the mechanisms of cervical cancer development by studying the role of the vaginal microecology. The identified biomarkers related to the microbiota and local immunity at various HPV infection statuses may help develop new approaches to the diagnosis and prevention of cervical dysplasia and cervical cancer.