The influence of human papillomaviruses on the cytokine profile of blood serum and cervical mucus in cervical intraepithelial neoplasia

Objective. To investigate the influence of different types of human papillomavirus (HPV) and the level of viral load on the profiles of cytokine factors in cervical mucus and blood serum in cervical intraepithelial neoplasia. Material and methods. The study included 30 healthy women (control group) and 60 patients infected with HPV and diagnosed with cervical intraepithelial neoplasia of mild (LSIL, n=30) and severe (HSIL, n=30) grade. The levels of immunoregulatory factors were determined in cervical mucus and blood serum using the Pro Human Cytokine 27-plex Assay (Bio-Rad Laboratories, Inc., USA) on a Luminex 200 analyzer (USA). To assess differences between groups categorized by the presence of the virus, HPV type, and viral load level, one-way analysis of variance (ANOVA) and a two-sample t-test with unequal variances were used. Results. In LSIL, compared to the control group, opposite and significant differences were found in the levels of IL-4, IL-8, FGF, IL-1b, IL1-ra, IL-2, IL-5, IP-10, MCP-1, and PDGF-BB in both blood and cervical mucus. In HSIL, changes were observed in the levels of FGF, IL-10, IL-8, IL-17A, TNF-a, and VEGF. In the blood serum of all HPV-positive patients, regardless of the virus strain, a decrease in the levels of IL-17A, IL-2, IL-5, IL-9, and PDGF-BB, and an increase in the levels of IL-4, IL-7, IL-10, and the IL-10/IL-17A ratio were found compared to healthy women. In the cervical mucus of all virus-positive patients, compared to the HPV-negative group, elevated levels of IL-1b, VEGF, FGF, and a significant decrease in the levels of IL-8 and IP-10 were observed. Conclusion. The main influence on the local and systemic cytokine profile in cervical intraepithelial neoplasia is exerted by the presence of HPV infection in the body, regardless of the virus type and the level of viral load.