Cervical Stage II Intraepithelial Neoplasia: Antivirals Efficacy
Authors:   Penza Institute of Advanced Physician Training, a branch of the Russian Medical Academy of Continuing Professional Education (a Federal Government-funded Educational Institution of Advanced Professional Education), Russian Federation Ministry of Health, Vinogradova O.P. ,   Penza, Russian Federation, Andreeva N.A. ,   N. P. Ogarev Mordovian National Research State University; Saransk, Russian Federation, Artemova O.I. ,   Penza State University (a Federal Government-funded Educational Institution of Higher Education); Penza, Russian Federation, Epifanova O.V. ,   Penza Institute of Advanced Physician Training, a branch of the Russian Medical Academy of Continuing Professional Education (a Federal Government-funded Educational Institution of Advanced Professional Education), Russian Federation Ministry of Health; Penza, Russian Federation
Published: April 2022

Study Objective: To assess the efficacy of an antiviral in the management of HPV-associated cervical stage II intraepithelial neoplasia (CIN II), using the analysis of the apoptotic marker levels and cytokine profile — caspase 3 and 9, interferon (INF) γ, interleukin (IL) 18. Study Design: Perspective study. Materials and Methods. We examined 126 women of reproductive age. The study included two groups: controls (40 relatively healthy fertile women without any cervical pathologies and HPV) and a group of 86 women with HPV-associated CIN II. All subjects underwent an examination; and their cytokine response and apoptotic marker level were assessed. All patients in CIN II group had the affect area excised. 43 post-excision women were followed up (sub-group A); other 43 subjects had surgery and an antiviral (sub-group B). The antiviral was administered subcutaneously once daily, 3 injections before and 3 injections after the excision. The primary efficacy criteria were absence of HPV or reduction in the viral load below significant values, and absence of pathology relapses after 6 and 12 months of the study. Study Results. In subjects with CIN II, pre-therapy caspase 3 and 9 levels were significantly higher vs controls; INF-γ was 1.8 times higher than in controls, and mean IL-18 concentration was considerably lower (p < 0.05 in both cases). In sub-groups A and B, caspase 3 and 9 concentration in 3 and 6 months after therapy also differed significantly from controls, and in 6 months, caspase 3 and 9 concentration in sub-group В was considerably lower than in sub-group А. Women in sub-groups А and В demonstrated statistically significant difference in cytokine profile: in both sub-groups, INF-γ concentration in 10 days increased, while in 12 months it almost reached its baseline value. IL-18 in sub-group B in 10 days and 12 months was significantly higher than in sub-group А. Conclusion. The results of the study demonstrate high HPV elimination and reduction in relapse probability after excision in patients with CIN II with the use of antivirals. Keywords: human papilloma virus, cervical intraepithelial neoplasia, caspase 3, caspase 9, apoptosis, cytokines, interleukin18, tumour necrosis factor α, interferon γ, cervical cancer, genetic typing, high risk of cancer.