Application of a Cytokine Complex in the Treatment of Squamous Intraepithelial Lesion of the Cervix

The dissertation is devoted to the study of the efficacy of the application of a local cytokine complex — the drug «Superlymph» — in the comprehensive treatment of squamous intraepithelial lesions of the cervix caused by human papillomavirus. The research encompasses the epidemiology of papillomavirus infection, the features of cellular and humoral immunity in intraepithelial dysplasias, and clinical approaches to the treatment of this disease. A clinico-immunological examination of patients with low-grade and high-grade squamous intraepithelial lesion was conducted, and the influence of immunomodulatory therapy on the clinical course of the disease was evaluated. On the basis of the obtained data, a differentiated treatment methodology has been developed, including monotherapy with the drug «Superlymph», combined treatment involving laser vaporization, and the use of the drug in conjunction with etiotropic therapy of concomitant infections. The results of the research have been implemented in clinical practice and in the educational process of the medical university, which confirms their practical significance for gynecological care.

Relevance of the Research. Sexually transmitted diseases are a serious medico-social problem worldwide, and among other sexually transmitted infections, genital tract papillomavirus infection (HPV) occupies one of the leading positions and is considered the principal factor of cervical carcinogenesis. The causative agent — a DNA-containing human papillomavirus (HPV) — is an oncogenic virus possessing more than 40 distinct antigenic types and is an obligate epitheliotrope. According to numerous sources, there is currently no trend toward a decline in the incidence of papillomavirus infection, which is associated with insufficient clinical-diagnostic examination of patients, the combination of HPV with other sexually transmitted infections, and the presence of latent HPV carriage. The prolonged persistence of the virus in the intermediate layer of the multi-layered epithelium of the cervix, which frequently leads to recurrence of the process in patients with disrupted immune equilibrium, determines the principal difficulties in combating this disease. The absence of a clear understanding among practitioners of the necessity of a pathogenetic approach to comprehensive therapy and the conduct of specialized diagnostics aimed at identifying viral pathology leads to an increase in the incidence of papillomavirus infection. It should be noted that in the United States, the National Cancer Institute, with the aim of establishing a unified understanding of precancerous conditions of the cervix among cytologists and pathomorphologists, recommended a cytological classification — the Bethesda system (1989). In accordance with this classification, cervical changes associated with dysplasia are proposed to be designated as low-grade and high-grade squamous intraepithelial lesions. The basis for distinguishing low-grade and high-grade squamous intraepithelial lesions was the results of clinico-morphological and virological investigation of cervical pathology. Squamous intraepithelial lesion of the cervix caused by HPV is most frequently encountered in women of reproductive age, and given that certain HPV serotypes are considered an etiological factor in the genesis of squamous cell carcinoma of the cervix, the development of the most effective diagnostic and treatment methods is necessary in order to restore the reproductive health of women. Attempts are being made to treat HPV using various agents; however, limited success and a high recurrence rate compel the search for new remedies that could be more effective, would not disrupt the microecology, and would, on the contrary, restore it, thereby helping the immune system to cope with the viral infection without the use of specific antiviral agents. Goal of the Research. To increase the efficacy of the treatment of squamous intraepithelial lesion of the cervix caused by human papillomavirus through the use, in comprehensive therapy, of the local application of a cytokine complex — the drug «Superlymph». Tasks of the Research. 1. To identify concomitant diseases of the lower genital tract in patients with squamous intraepithelial lesion of the cervix. 2. To determine the features of the clinical course depending on various degrees and the extent of ectocervical involvement in squamous intraepithelial lesion of the cervix. 3. To evaluate the cellular and humoral components of immunity, the interferon status, and the local cytokine spectrum in patients with intraepithelial papillomatosis. 4. To determine the influence of local immunomodulatory therapy on the clinical course of squamous intraepithelial lesion of the cervix in monotherapy, combined treatment (laser vaporization + Superlymph), and in conventional treatment (with lipofilcon). 5. To develop a scientifically grounded approach to differentiated treatment of patients with various forms of squamous intraepithelial lesion of the cervix, including etiotropic therapy, correction of dysbiotic disturbances (for example, for chlamydia — vilprafen and zlemik, for candidiasis — orungal and zlemik), and the use of the drug Superlymph. Scientific Novelty. For the first time, the influence of a local cytokine complex on the clinical course of squamous intraepithelial lesion of the cervix has been determined. The features of the clinical course depending on various degrees and the extent of ectocervical involvement in squamous intraepithelial lesion of the cervix have been established. An investigation of the state of the immune system in this category of patients has been conducted, with the determination of the influence of local immunomodulatory therapy. On the basis of the obtained data, a methodology for local therapy with the drug Superlymph has been developed in order to increase the efficacy of pathogenetically grounded treatment of squamous intraepithelial lesion of the cervix, both as monotherapy and as combined treatment (laser vaporization + Superlymph). Practical Significance. The results obtained have contributed to the development of the most optimal tactics for managing patients with squamous intraepithelial lesion of the cervix, early diagnosis of the disease, monitoring the efficacy of the conducted therapy, and pathogenetically grounded treatment. Implementation of the Research Results in Practice. The results of the research have been implemented in clinical practice and in the educational process of the Department of Obstetrics and Gynecology of the Clinical Faculty of the Moscow Medical Academy of Postgraduate Education, and are used in the work of gynecological departments of City Clinical Hospital No. 36. Main Propositions for Defense. 1. The immunosuppressive state of the organism is a provoking factor in the development of intraepithelial papillomatosis of the cervix caused by HPV. 2. Patients with intraepithelial papillomatosis of the cervix must be included in comprehensive treatment with the local immunomodulator Superlymph, regardless of the degree of cervical involvement. 3. In order to improve treatment efficacy and achieve sustained results, repeated courses of the drug Superlymph must be conducted 12 months after treatment. 4. The use of the drug Superlymph is pathogenetically grounded due to the presence of a natural combination of cytokines and allows achieving complete recovery in 85% of patients with low-grade intraepithelial lesion without the application of destructive treatment methods, and in 94.2% of patients with high-grade intraepithelial lesion when combined with laser vaporization or conization of the cervix. Publications. Based on the materials of the dissertation, 6 works have been published, including a work in the journal «Voprosy ginekologii, akusherstva i perinatalogii» recommended by the VAK of Russia.