GynecologyGynecology2079-56962079-5831Consilium Medicum3012710.26442/20795696.2019.1.190284Research ArticleLocal cytokine therapy in a comprehensive treatment of HPV-associated cervical diseasesAbakarovaPatimat RMClSc, PhD, Researcher of the Scientific and Polyclinic Department-PrilepskayaVera NMD, PhD, Professor, Deputy director for Science, Head of the Scientific and Polyclinic DepartmentVPrilepskaya@mail.ruMezhevitinovaElena AMD, PhD, DSc, Leading Researcher of the Scientific and Polyclinic Department-DonnikovAndrei EMClSc, PhD, Head of the Laboratory of molecular and genetic methods-V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation15022019211283209042020Copyright © 2019, Consilium Medicum2019Aim. To analyze an efficacy of monotherapy and combined therapy (an immunomodulator + radio wave ablation) in patients with low-grade squamous intraepithelial lesion (L-SIL) caused by HPV infection. Materials and methods. The study included 210 women with human papillomavirus infection which was identified using real-time polymerase chain reaction (PCR). All women underwent a comprehensive examination which included history taking, general and gynecological examinations, extended colposcopy and a bacterioscopy of Gram-stained vaginal smears. A quantitative determination of vaginal microflora composition by PCR was carried out. Conclusion on either inflammatory response is present or absent was made on the basis of an inflammation index magnitude: with a value of more than 60% indicating a presence of local inflammation signs. Based on cervical cytology data a group consisting of 79 women who had L-SIL was formed. Patients were divided into 2 subgroups: the main one (n=45) who received combined treatment with radio wave ablation + an immunomodulator and a control one (n=34) who received only local monodestruction of L-SIL foci followed etiotropic treatment. Results and discussion. An efficacy of combined treatment which included radio wave ablation + an immunomodulator was higher compared to monodestruction only - 86.7% vs 64,7% respectively. It is important that by 6th month of follow-up a relapse of human papillomavirus infection occurred in 4.5 and 23.5% of patients of main and control groups respectively. Local inflammation was assessed as positive with an inflammation index of more than 60%. So after 6 months of follow-up this indicator decreased by 83.3 and 54.2% in the 1st and 2nd groups respectively. Clinical manifestations of an inflammatory process in the cervix was observed only with CIN recurrence. In addition, combined therapy provides a higher rate of human papillomavirus elimination at 6 months and faster cervix epithelization followed treatment by ablation.human papillomavirus infectionradio wave ablationcombined treatmentпапилломавирусная инфекциярадиоволновая деструкциякомбинированное лечение[Сухих Г.Т., Прилепская В.Н. Профилактика рака шейки матки: руководство для врачей. 3-е изд. М.: МЕДпресс-информ, 2012. [Sukhikh G.T., Prilepskaya V.N. Profilaktika raka sheiki matki: rukovodstvo dlia vrachei. 3-e izd. Moscow: MEDpress-inform, 2012 ]][Bruni L, Diaz M, Castellsagué X et al. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological i ndings. J Infect Dis 2010; 202 (12): 1789-99.][Munoz N, Bosch F, Sanjos S et al. International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348 (6): 518-27.][Tang Y, Zheng L, Yang S et al. Epidemiology and genotype distribution of human papillomavirus (HPV) in Southwest China: a cross-sectional five years study in non-vaccinated women. Virology J 2017; 14: 84.][Smith J.S, Lindsay L, Hoots B et al. Human papillomavirus type distribution in invasivе cancer and high-grade cervical lesions: A meta-analysis update. Int J Cancer 2007; 121: 621-32.][Бебнева Т.Н. Некоторые аспекты папилломавирусной инфекции. Гинекология. 2007; 9 (1): 19-22. [Bebneva T.N. Nekotorye aspekty papillomavirusnoi infektsii. Gynecology. 2007; 9 (1): 19-22.]][Долгушина В.Ф., Ахматова А.Н., Телешева Л.Ф., Абрамовских О.С. Персистенция папилломавирусной инфекции у женщин с хроническим цервицитом. Уральский мед. журн. 2010; 3 (68): 91-4. [Dolgushina V.F., Akhmatova A.N., Telesheva L.F., Abramovskikh O.S. Persistentsiia papillomavirusnoi infektsii u zhenshchin s khronicheskim tservitsitom. Ural'skii med. zhurn. 2010; 3 (68): 91-4 ]][Spitzer M. Screening and management of women and girls with human papillomavirus infection. Gynecol Oncol 2007; 107: 2 (Suppl. 1): 14-9. https://doi. org/10.1016/j.ygyno.2007.07.069][Weaver B, Shew M, Qadadri B et al. Low-level persistence of human papillomavirus 16 DNA in a cohort of closely followed adolescent women. J Med Virol 2011; 83 (8): 1362-9.][Манухин И.Б., Минкина Г.Н., Левченко Г.М., Гурин В.Е. Патогенетическое обоснование комплексного лечения папилломавирусной инфекции шейки матки. Журн. акушерства и женских болезней. Спец. выпуск. 1998. [Manukhin I.B., Minkina G.N., Levchenko G.M., Gurin V.E. Patogeneticheskoe obosnovanie kompleksnogo lecheniia papillomavirusnoi infektsii sheiki matki. Zhurn. akusherstva i zhenskikh boleznei. Spets. vypusk. 1998 ]][Сухих Г.Т., Матвеева Н.К., Аполихина И.А. и др. Показатели иммунитета у больных с папилломавирусной инфекцией гениталий. Акушерство и гинекология. 2002; 2: 20-5. [Sukhikh G.T., Matveeva N.K., Apolikhina I.A. et al. Pokazateli immuniteta u bol'nykh s papillomavirusnoi infektsiei genitalii. Akusherstvo i ginekologiia. 2002; 2: 20-5 ]][Роговская С.И., Жданов А.В., Логинова Л.С. и др. Состояние системы интерферонов у женщин с папилломавирусной инфекцией гениталий при использовании иммуномодулирующей терапии. Бюл. эксперим. биологии и медицины. 2002; 131 (11): 538-42. [Rogovskaia S.I., Zhdanov A.V., Loginova L.S. et al. Sostoianie sistemy interferonov u zhenshchin s papillomavirusnoi infektsiei genitalii pri ispol'zovanii immunomoduliruiushchei terapii. Biul. eksperim. biologii i meditsiny. 2002; 131 (11): 538-42 ]][Seresini S, Origoni M, Lillo F at al. IFN-gamma produced by human papilloma virus-18 E6-spesific CD4+ T-cells predicts the clinical outcome after surgery with high-grade cervical lesions. J Immunol 2007; 179: 7176-83.][Дубенский В.В., Кузнецов В.П., Беляев Д.Л., Слюсарь Н.Н. Эффективность иммунокоррекции цитокинами при лечении папилломавирусной инфекции. Журн. микробиологии, эпидемиологии и иммунобиологии. 2001; 5: 54-8. [Dubenskii V.V., Kuznetsov V.P., Beliaev D.L., Sliusar' N.N. Effektivnost' immunokorrektsii tsitokinami pri lechenii papillomavirusnoi infektsii. Zhurn. mikrobiologii, epidemiologii i immunobiologii. 2001; 5: 54-8 ]][Кореева В.Н., Доброхотова Ю.Э. Применение локальной цитокинотерапии в акушерско-гинекологической практике. Рос. вестн. акушера-гинеколога. 2013; 5: 99-104. [Koreeva V.N., Dobrokhotova Iu.E. Primenenie lokal'noi tsitokinoterapii v akushersko-ginekologicheskoi praktike. Ros. vestn. akushera-ginekologa. 2013; 5: 99-104 ]][Kanodia S, Da Silva D.M, Kast W.M. Recent advances in strategies for immunotherapy of human papillomavirus-induced lesions. Int J Cancer 2008; 122: 247-59.]