Kashtalian N. Optimization of management of reproductive age women with cervical intraepithelial neoplasia associated with papillomaviral infection

Thesis for the degree of candidate of medical sciences (PhD) in the specialty 14.01.01 – Obstetrics and Gynecology. – The Odesa National Medical University of the Ministry of Health of Ukraine, Odesa, 2019. The thesis is devoted to the efficacy improvement in diagnostics and treatment of cervical intraepithelial neoplasia (CIN) in women of reproductive age with HPV infection by the usage of modern surgical energies and introduction of differentiated approaches to the management of those patients. It is established that the most important risk factors of CIN development in women of reproductive age are high and low viral load of high risk HPV, high amount of sexual partners, smoking, age from 30 to 35 years and early sexual debut. It is revealed that diagnostic value of traditional cytomorphological tests and colposcopic examination with using international nomenclature in diagnostics of CIN II–III is non-optimal. Diagnostic value of RCI colposcopy in diagnostics of CIN II–III is better despite still being suboptimal. These data prove that it is necessary to use a combination of different methods of diagnostics to create management algorithm of reproductive age women with cervical intraepithelial neoplasia associated with HPV infection. It is established that methylation of WIF1 and DKK4 genes is aberrant in CIN and increases in accordance to the stage of pathological changes and can be used in differential diagnostics of CIN II–III and cervical cancer. Immunecytochemical biomarker р16 has high sensitivity and specificity of CIN II–III diagnostics and can be used for diagnostics of medium and high dysplasia on preexcisional stage. Immunecytochemical biomarker Кі-67 has high sensitivity and specificity of CIN III diagnostics and can be used in differential diagnostics of CIN III on preoperative stage. It is determined that usage of cold plasma destruction in treatment of CIN I–II in reproductive age women allows to considerably lessen discharge duration after treatment, term of epithelization, increases the chances of viral elimination and has less complications as compared to cryotherapy. Usage of radioexcision leads to lessening of discharge duration and terms of epithelization after surgery, increases the chances of viral elimination and has less complications as compared to traditional electrosurgery. These results allowed to justify management algorithm of reproductive age women with cervical intraepithelial neoplasia associated with HPV infection by taking into consideration results of RCI colposcopy, state of immunecytochemical biomarkers p16 and Ki-67 and by using cold plasma therapy and radio surgery of cervical precancerous lesions.