Immunomodulatory therapy in the complex treatment of HPV-associated cervical lesions

DOI

https://dx.doi.org/10.18565/aig.2022.6.129-138

Radzinskiy V.Е., Gizinger O.А., Ordiyants I.М., Selikhova M.S., Mingaleva N.V., Lebedenko E.Yu., Katkova N.Yu., Elgina S.I., Dovletkhanov E.R., Meteleva T.A.
1) Рeoples’ Friendship University of Russia (RUDN University), Moscow, Russia; 2) Volgograd State Medical University, Ministry of Health of Russia, Volgograd, Russia; 3) Kuban State Medical University, Ministry of Health of Russia, Krasnodar, Russia; 4) Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don, Russia; 5) Privolzhsky Research Medical University, Ministry of Health of Russia, Nizhny Novgorod, Russia; 6) Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo, Russia; 7) Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 8) Academician E.A. Wagner Perm State Medical University, Ministry of Health of Russia, Perm, Russia

Relevance: Dysplasia is one of the results of the transformative effects of the human papillomavirus (HPV). Exposure to the virus more frequently leads to cervical dysplasia, and its progressive development leads to tumor progression. Monitoring and medical examination of HPV-carriers, timely selection of methods for their recovery is a reserve for reducing cervical neoplasia and cervical cancer. The probable benefit of immunomodulatory therapy as a way to reduce the risk of HPV-associated cervical lesions cannot be considered proven due to insufficient number and quality of evidence-based medicine studies.
Objective: To evaluate the effect of immunomodulating medications on changes in colposcopic and cytological characteristics in HPV-associated cervical lesions.
Materials and methods: This was an open multicenter randomized study conducted in 2020–2021. Five hundred women with HPV-associated cervical lesions registered electronically and monitored in women’s health clinics in 7 regions of the Russian Federation were included in the study. The research followed the multicenter comparative observational program “Evaluation of the efficacy and safety of Immunomax in the complex therapy of benign cervical dysplasia with confirmed HPV infection” which was developed in 2020–2021 in the Russian Federation (http://richt.ru/; http://greta.pro/). There were the following criteria for inclusion in the program: HPV-associated cervical diseases (ICD-10: N87.X + B97.7 CIN I–II), age from 18 to 55 years (median age 33 years). The main therapy was destructive or excisional exposure, which was prescribed to all participants of the study after signing an informed consent. Immunomax, Allokin-alfa, medications with INN inosine pranobex, which have immunotropic effects, were selected as immunomodulatory medications and were used in complex therapy. The participants of the study were randomized into groups depending on the administered immunomodulatory medications: 114 women received Immunomax, 95 women received Allokin-alfa, 154 women took INN inosine pranobex, 59 women underwent surgical treatment but they did not receive immunomodulatory therapy. Control studies confirming the effectiveness of the therapy were conducted 3 and 6 months after the completion of treatment.
Results: Statistical analysis of the results of the study confirmed the importance of immunomodulatory therapy in eliminating HPV and normalizing colposcopic picture. The effectiveness of combined treatment with the use of immunomodulatory medications was higher than one after destruction without administration of immunotropic medications. The study conducted 3 and 6 months after the treatment showed that frequency of elimination of highly oncogenic HPV was significantly higher in groups of patients who received surgical treatment in combination with Immunomax, Allokin-alpha, medications with INN inosine pranobex; normalization of colposcopic picture was observed in all comparison groups.
Conclusion: The data obtained from 7 regions of the Russian Federation were added to a specially developed electronic register of patients with HPV-associated cervical lesions. The findings showed that surgical treatment in combination with immunomodulatory therapy resulted in a higher frequency of HPV elimination and normalization of the colposcopic picture than surgery without the use of immunomodulatory therapy.

human papillomavirus

cervical dysplasia

immunomodulatory therapy

Full text (in Russian)

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Received 09.06.2022

Accepted 27.06.2022

Viktor Е. Radzinskiy, Corresponding Member of the Russian Academy of Sciences, Dr. Med. Sci., Head of the Department of Obstetrics and Gynecology with a Perinatology Course, Medical Institute of RUDN University (Moscow, Russia), radzinsky@mail.ru, https://orcid.org/0000-0003-4956-0466
Oksana А. Gizinger, Dr. Sci. (Bio), Professor, Department of Microbiology and Virology, Medical Institute of RUDN University (Moscow, Russia), +7(919)319-46-04, OGizinger@gmail.com, https://orcid.org/0000-0001-9302-0155, 117198, Russia, Moscow, Miklukho-Maklaya str., 8.
Irina M. Ordiyants, Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology with a Perinatology Course, Medical Institute of RUDN University (Moscow, Russia), ordiants_im@rudn.university, https://orcid.org/0000-0001-5882-9995
Marina S. Selikhova, Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology, Volgograd State Medical University, Ministry of Health of Russia (Volgograd, Russia), selichovamarina@yandex.ru, https://orcid.org/0000-0002-4393-6111
Natalya V. Mingaleva, Dr. Med. Sci., Chief Freelance Specialist in Outpatient Obstetric and Gynecological Care of the Ministry of Health of the Krasnodar Territory; Professor, Department of Obstetrics, Gynecology and Perinatology, Kuban State Medical University, Ministry of Health of Russia (Krasnodar, Russia),
mingalevaN008@yandex.ru, https://orcid.org/0000-0001-5440-3145
Elizaveta Yu. Lebedenko, Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology No. 3, Rostov State Medical University, Ministry of Health of Russia
(Rostov-on-Don, Russia), lebedenko08@mail.ru, https://orcid.org/0000-0003-2602-1486
Nadezhda Yu. Katkova, Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Additional Vocational Education, Privolzhsky Research Medical University, Ministry of Health of Russia (Nizhny Novgorod, Russia), katkova_nu@inbox.ru, SPIN-код: 7967-5759, Author ID: 340045.
Svetlana I. Elgina, Dr. Med. Sci., Professor, Department of Obstetrics and Gynecology named after G.A. Ushakova, Kemerovo State Medical University, Ministry of Health
of Russia (Kemerovo, Russia), elginas.i@mail.ru, https://orcid.org/0000-0003-2601-5678
Elmira R. Dovletkhanova, PhD, Senior Researcher, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry
of Health of Russia (Moscow, Russia), eldoc@mail.ru, https://orcid.org/0000-0003-2835-6685
Tatyana A. Meteleva, Assistant, Department of Obstetrics and Gynecology No. 1, Ye.A. Vagner Perm State Medical University, Ministry of Health of Russia (Perm, Russia), ta.meteleva@mail.ru, https://orcid.org/0000-0002-1448-1840
Corresponding author: Oksana A. Gizinger, OGizinger@gmail.com

Authors’ contributions: Radzinskiy V.E. – research and analytical work, article writing and design, editing, approval of the manuscript for publication; Gizinger O.A. – conducting a study, research and analytical work, analysis of the obtained results, article writing and design, editing; Ordiyants I.M., Selikhova M.S., Mingaleva N.V., Lebedenko E.Yu., Katkova N.Yu., Elgina S.I., Dovletkhanova E.R., Meteleva T.A. – conducting a study, study design, justification of research methods.
Conflicts of interest: The authors have confirmed that there is no conflicts of interest to disclose.
Funding: The article was performed in accordance with the multicenter comparative observational program "Evaluation of the efficacy and safety of Immunomax in the treatment of benign cervical dysplasia with confirmed HPV infection" with the participation of LLC "RICHT" and JSC "Avexima".
Acknowledgement: The authors of the article express their gratitude to the obstetricians and gynecologists who participated in the research and development of the electronic register GRETA (http://greta.pro/) in 7 regions of the Russian Federation.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Radzinskiy V.Е., Gizinger O.А., Ordiyants I.М., Selikhova M.S., Mingaleva N.V., Lebedenko E.Yu., Katkova N.Yu., Elgina S.I., Dovletkhanov E.R., Meteleva T.A. Immunomodulatory therapy in the complex treatment of HPV-associated cervical lesions.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 6: 129-138 (in Russian)
https://dx.doi.org/10.18565/aig.2022.6.129-138

Immunomodulatory therapy in the complex treatment of HPV-associated cervical lesions

Radzinskiy V.Е., Gizinger O.А., Ordiyants I.М., Selikhova M.S., Mingaleva N.V., Lebedenko E.Yu., Katkova N.Yu., Elgina S.I., Dovletkhanov E.R., Meteleva T.A.

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