The Efficacy of Human Papillomavirus Elimination during Treatment of Cervical Disorders
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, Artemova O.I. ,   Penza State University (a Federal Government-funded Educational Institution of Higher Education); Penza, Russian Federation
Published: January 2021

Study Objective: To assess the efficacy of antiviral medications, using the apoptotic markers caspase-3 and caspase-9, in the treatment of cervical disorders accompanied by papillomavirus infection. Study Design: This was a prospective study. Materials and Methods: One hundred and seventy women with a positive human papillomavirus (HPV) test, aged 18 to 45, participated in the study. Group I consisted of 60 women with histologically confirmed cervical leukoplakia; Group II was made up of 55 patients with cervical intraepithelial neoplasia (CIN) I; and Group III comprised 55 women with CIN II. The control group consisted of 40 healthy women. All participants underwent a standard examination and had measurements taken for levels of caspase-1, caspase-3, and caspase-9, which were used to assess changes in their apoptotic programs. During the study, the patients with HPV were divided into subgroups. In the cervical leukoplakia group, 34 women (subgroup Ia) were only monitored and 26 women (subgroup Ib) received antiviral treatment. Similarly, in the CIN I group, 27 patients (subgroup IIa) were only monitored and 28 women (subgroup IIb) received antiviral drugs. In the CIN II group, all patients underwent excision of their lesions. According to the study design, 28 women who had undergone excision had monitoring alone (subgroup IIIa) and for 27 participants the surgical treatment was combined with an antiviral medication (subgroup IIIb). The efficacy of the treatment regimens was assessed three and six later by cytology and colposcopy data and levels of caspase-3 and caspase-9. Treatment efficacy was assessed chiefly by the presence or absence of HPV or reduction in viral load below significant levels. Study Results: After three and six months, viral load reduction in all subgroups of women who received antiviral treatment was greater and more of these women had a negative HPV test (after three and six months the overall efficacy was 11.7% vs. 30.7% and 20.5% vs. 42.3% in subgroups Ia and Ib, respectively; 7.4% vs. 21.4% and 22.2% vs. 35.7% in subgroups IIa and IIb, respectively; and 75% vs. 85.2% and 64.2% vs. 92.6% in subgroups IIIa and IIIb, respectively). Caspase-3 and caspase-9 levels decreased in both the subgroups that had monitoring alone and the subgroups that received combination treatment, but in the latter case they were closer to the control group’s levels. Correlation analysis revealed a strong direct relationship between clinically significant viral load and caspase-3 levels (rху = 0.79) and a moderate direct relationship between caspase-9 levels and high viral load (rху = 0.58). Conclusion: The proposed comprehensive approach, including antiviral therapy, to the treatment of HPV-associated cervical disorders such as leukoplakia, CIN I and CIN II, has higher clinical efficacy than monitoring over time alone or only the excision of lesions (in patients with CIN II). This is because of its effects on the system of natural killers and stimulation of the ability of cytotoxic lymphocytes to identify and destroy defective cells. Keywords: human papillomavirus, apoptosis, caspases, dysplasia, leukoplakia.