rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/2410-1893-2023-10-4-9DDDGIUrpmj-960Research ArticleОбзорыReviewВирус папилломы человека высокого канцерогенного риска: распространенность, связь с клинико-морфологическими характеристиками инвазивного рака шейки маткиHigh-risk human papillomavirus: prevalence, association with clinical and morphological characteristics of invasive cervical cancerhttps://orcid.org/0000-0002-5027-5331МкртчянЛ. С.MkrtchianL. S.

 

Мкртчян Лиана Сирекановна – д.м.н., ведущий научный сотрудник Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0002-5027-5331, SPIN: 3352-0814, AuthorID: 147713, Scopus Author ID: 6601999343, ResearcherID: JBJ-0493-2023

 

Liana S. Mkrtchian – Dr. Sci. (Medicine), Senior Research Scientist of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-5027-5331, SPIN: 3352-0814, AuthorID: 147713, Scopus Author ID: 6601999343, ResearcherID: JBJ-0493-2023

liana6969@mail.ruhttps://orcid.org/0000-0003-3565-1981КиселеваВ. И.KiselevaV. I.

 

Киселева Валентина Ивановна – к.б.н., ведущий научный сотрудник Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0003-3565-1981, SPIN: 2865-4070, AuthorID: 81608, Scopus Author ID: 7004413804, ResearcherID: T-1073-2017

 

Valentina I. Kiseleva – Cand. Sci. (Biology), Senior Research Scientist of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0003-3565-1981, SPIN: 2865-4070, AuthorID: 81608, Scopus Author ID: 7004413804, ResearcherID: T-1073-2017

 

kivapim@mail.ruhttps://orcid.org/0009-0009-6821-5335БойкоБ. В.BoykoB. V.

 

Бойко Борис Викторович – аспирант Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0009-0009-6821-5335, ResearcherID: JDC-4676-2023

 

Boris V. Boyko – PhD Student of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0009-0009-6821-5335, ResearcherID: JDC-4676-2023

pappyb67@mail.ruhttps://orcid.org/0000-0003-1842-156XКрикуноваЛ. И.KrikunovaL. I.

 

Крикунова Людмила Ивановна – д.м.н., профессор, главный научный сотрудник Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0003-1842-156X, SPIN: 2845-6710, AuthorID: 93505, Scopus Author ID: 6506081959, ResearcherID: JCT-3165-2023

 

Liudmila I. Krikunova – Dr. Sci. (Medicine), Professor, Chief Scientist of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0003-1842-156X, SPIN: 2845-6710, AuthorID: 93505, Scopus Author ID: 6506081959, ResearcherID: JCT-3165-2023

krikunova_li@mail.ruhttps://orcid.org/0000-0002-8580-933XПетровВ. А.PetrovV. A.

 

Петров Владимир Александрович – д.м.н., профессор, заведующий Научно-образовательным отделом Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0002-8580-933X, SPIN: 1833-0060, AuthorID: 236272, Scopus Author ID: 57199919288, ResearcherID: HMV-0482-2023

 

Vladimir A. Petrov – Dr. Sci. (Medicine), Professor, Head of the Scientific and Educational Department of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-8580-933X, SPIN: 1833-0060, AuthorID: 236272, Scopus Author ID: 57199919288, ResearcherID: HMV-0482-2023

vapetrov1959@mail.ruhttps://orcid.org/0000-0002-7819-2730ГусароваВ. Р.GusarovaV. R.

 

Гусарова Виктория Романовна – аспирант Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0002-7819-2730, ResearcherID: HMD-3406-2023

 

Victoria R. Gusarova – PhD Student of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-7819-2730, ResearcherID: HMD-3406-2023

bingooo444@gmail.comhttps://orcid.org/0000-0001-7689-6032ИвановС. А.IvanovS. A.

 

Иванов Сергей Анатольевич – д.м.н., профессор, член-корреспондент РАН, директор Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация; профессор кафедры онкологии и рентгенорадиологии им. В. П. Харченко Медицинского института ФГАОУ ВО «Российский университет дружбы народов», г. Москва, Российская Федерация

ORCID: https://orcid.org/0000-0001-7689-6032, SPIN: 4264-5167, AuthorID: 710405, Scopus Author ID: 16070399200, ResearcherID: N-8221-2017

 

Sergei A. Ivanov – Dr. Sci. (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences (RAS), Director of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation; Professor of the Department of Oncology and Radiology named after V.P. Kharchenko at the Medical Institute. V.P. Kharchenko Medical Institute of Peoples' Friendship University of Russia, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0001-7689-6032, SPIN: 4264-5167, AuthorID: 710405, Scopus Author ID: 16070399200, ResearcherID: N-8221-2017

 

oncourolog@gmail.comhttps://orcid.org/0000-0001-8784-8415КапринА. Д.KaprinA. D.

 

Каприн Андрей Дмитриевич – д.м.н., профессор, академик РАН, академик РАО, директор Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Москва, Российская Федерация; генеральный директор ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация; заведующий кафедрой онкологии и рентгенорадиологии им. В. П. Харченко Медицинского института ФГАОУ ВО «Российский университет дружбы народов», г. Москва, Российская Федерация

ORCID: https://orcid.org/0000-0001-8784-8415, SPIN: 1759-8101, AuthorID: 96775, Scopus Author ID: 66002709853, ResearcherID: K-1425-2014

 

 

Andrey D. Kaprin – Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences, Academician of the Russian Academy of Education, Director of P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation; General Director of National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation; Head of the Department of Oncology and Radiology named after V.P. Kharchenko at the Medical Institute. V.P. Kharchenko Medical Institute of Peoples' Friendship University of Russia, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0001-8784-8415, SPIN: 1759-8101, AuthorID: 96775, Scopus Author ID: 66002709853, ResearcherID: K-1425-2014

kaprin@mail.ruhttps://orcid.org/0000-0002-6136-8445ЗамулаеваИ. А.ZamulaevaI. A.

 

Замулаева Ирина Александровна – д.б.н., профессор, заведующая отделом радиационной биохимии Медицинского радиологического научного центра им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация

ORCID: https://orcid.org/0000-0002-6136-8445, SPIN: 9542-6211, AuthorID: 87777, Scopus Author ID: 6603693422, ResearcherID: R-4906-2016

 

Irina A. Zamulaeva – Dr. Sci. (Medicine), Professor, Head of the Department of Radiation Biochemistry of A. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation

ORCID: https://orcid.org/0000-0002-6136-8445, SPIN: 9542-6211, AuthorID: 87777, Scopus Author ID: 6603693422, ResearcherID: R-4906-2016

zamulaeva@mail.ruМедицинский радиологический научный центр им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации<p> г. Обнинск, Российская ФедерацияA. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation<p> Obninsk, Russian FederationМедицинский радиологический научный центр им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации<p> г. Обнинск, Российская ФедерацияA. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation<p> Obninsk, Russian FederationМедицинский радиологический научный центр им. А. Ф. Цыба – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Обнинск, Российская Федерация; <p> Российский университет дружбы народов, г. Москва, Российская ФедерацияA. Tsyb Medical Radiological Research Centre – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Obninsk, Russian Federation; <p> Peoples’ Friendship University of Russia, Moscow, Russian FederationМосковский научно-исследовательский онкологический институт им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации, г. Москва, Российская Федерация; <p> Национальный медицинский исследовательский центр радиологии Министерства здравоохранения Российской Федерации, г. Москва, Российская Федерация; <p> Российский университет дружбы народов, г. Москва, Российская ФедерацияNational Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation; <p> P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation; <p> Peoples' Friendship University of Russia, Moscow, Russian Federation202328112023104104118Copyright &#x00A9; Мкртчян Л.С., Киселева В.И., Бойко Б.В., Крикунова Л.И., Петров В.А., Гусарова В.Р., Иванов С.А., Каприн А.Д., Замулаева И.А., 20232023Мкртчян Л.С., Киселева В.И., Бойко Б.В., Крикунова Л.И., Петров В.А., Гусарова В.Р., Иванов С.А., Каприн А.Д., Замулаева И.А.Mkrtchian L.S., Kiseleva V.I., Boyko B.V., Krikunova L.I., Petrov V.A., Gusarova V.R., Ivanov S.A., Kaprin A.D., Zamulaeva I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/960Цель исследования

Цель исследования. Анализ современных источников литературы, посвященных изучению особенностей вируса папилломы человека (ВПЧ) высокого канцерогенного риска (ВКР), ассоциативных связей молекулярно-генетических параметров вируса с клинико-морфологическими характеристиками инвазивного рака шейки матки (РШМ).

Материалы и методы

Материалы и методы. Проведен поиск литературы в электронных базах данных National Center for Biotechnology Information Search database (PubMed/Medline), ResearchGate, Scopus, Web of Science, Cancer Tomorrow, Global cancer observatory, Cochrane Library, eLIBRARY, DisserCat. В поиске, охватывающем период с 1990 по 2022 гг., использованы ключевые слова на русском языке и в их переводе на английский язык: рак шейки матки, ВПЧ ВКР, ВПЧ-статус, генотип ВПЧ, множественная инфекция, интеграция ДНК, вирусная нагрузка. Было изучено более 120 полнотекстовых источников, в которых проводился анализ возможных корреляционных связей параметров папилломавирусной инфекции с клинико-морфологическими характеристиками цервикального рака. В обзор вошли данные 57 публикаций.

Результаты

Результаты. ВПЧ-инфицированными являются более 88 % больных инвазивным РШМ по данным большинства авторов. В этиологической структуре преобладают ВПЧ 16 (70–72 %), 18 (13–15 %) и 45 (5–7 %) типов. Невыявление ВПЧ ВКР при РШМ связывают, в том числе с ложноотрицательным результатом исследования. Проведенный анализ литературы показал наличие взаимосвязи ВПЧстатуса с возрастом, морфологической формой опухоли, вирусной нагрузкой, генотипом ВПЧ ВКР, наличием глубокой стромальной инвазии и метастатическим поражением лимфатических узлов. В отношении таких молекулярно-генетических параметров ВПЧ ВКР, как вирусная нагрузка и интеграция ДНК ВПЧ, ассоциативная связь с прогностически важными клиническими показателями опухоли шейки матки – стадия заболевания, локо-регионарная распространенность опухолевого процесса, гистологический тип опухоли – остается предметом дискуссий.

Заключение

Заключение. Во многих публикациях констатируется наличие корреляционной связи ВПЧ-статуса и генотипа ВПЧ ВКР с таким важным фактором, влияющим на результаты лечения РШМ, как морфологическая форма опухоли. Неоднозначные выводы по наличию взаимосвязи ряда молекулярно-генетических параметров ВПЧ-инфекции с основным прогностическим фактором – стадией заболевания (обусловленные как гетерогенностью выборок, использованием различных тест-систем, так и недостаточно полным учетом основных параметров ВПЧ-инфекции, прежде всего данных об интеграции вирусной ДНК), делают целесообразным дальнейшие исследования на репрезентативной группе больных с однородными диагностическими протоколами определения максимально полного спектра параметров ВПЧ ВКР. Кроме того, проведенный анализ литературы показал перспективность поиска предикторов эффективности специализированного лечения больных РШМ среди таких параметров ВПЧ-инфекции, как ВПЧ-статус, генотип ВПЧ ВКР и значимо связанный с ним физический статус вирусной ДНК.

Purpose of the study

Purpose of the study. Analysis of contemporary literature sources dedicated to the study of characteristics of high oncogenic risk human papillomavirus (HPV), associative links of the virus’s molecular-genetic parameters with the clinical and morphological characteristics of invasive cervical cancer (ICC).

Materials and methods

Materials and methods. A literature search was conducted in electronic databases including the National Center for Biotechnology Information Search database (PubMed/Medline), ResearchGate, Scopus, Web of Science, Cancer Tomorrow, Global cancer observatory, Cochrane Library, eLIBRARY, DisserCat. The search covered the period from 1990 to 2022 and utilized keywords in Russian and their English translations: cervical cancer, high oncogenic risk HPV, HPV status, HPV genotype, multiple infections, DNA integration, viral load. More than 120 full-text sources were studied, in which the analysis of possible correlations between the parameters of human papillomavirus infection and the clinical and morphological characteristics of cervical cancer was carried out. In review included data from 57 publications.

Results

Results. According to most authors, more than 88 % of patients with invasive ICC are HPV-infected. The etiological structure is dominated by HPV 16 (70–72 %), 18 (13–15 %), and 45 (5–7 %) types. Non-detection of HPV HR in cervical cancer is associated, including with a false negative result of the study.

The literature analysis showed the presence of an association between HPV status and age, morphological form of the tumor, viral load, high oncogenic risk HPV genotype, presence of deep stromal invasion, and metastatic involvement of lymph nodes. With regard to such molecular genetic parameters of HPV HR as viral load and HPV DNA integration, associative relationship with prognostic important clinical indicators of cervical tumor – the stage of the disease, the loco-regional prevalence of the tumor process, the histological type of tumor – remains the subject of discussion.

Conclusion

Conclusion. Many publications report a correlative link between HPV status and high oncogenic risk HPV genotype with such an important factor affecting ICC treatment outcomes as the morphological form of the tumor. Ambiguous conclusions on the presence of an association between a number of molecular-genetic parameters of HPV infection with the main prognostic factor – stage of the disease (due to the heterogeneity of samples, the use of different test systems, and the insufficiently complete account of the main parameters of HPV infection, especially data on viral DNA integration), make it advisable to conduct further research on a representative group of patients with homogeneous diagnostic protocols to determine the most complete spectrum of parameters of high oncogenic risk HPV. In addition, the conducted literature analysis showed the promise of searching for predictors of the effectiveness of specialized treatment of patients with ICC among such HPV infection parameters as HPV status, high oncogenic risk HPV genotype, and the significantly associated physical status of viral DNA.

вирус папилломы человекавысокий канцерогенный рискрак шейки маткигенотип ВПЧмножественная инфекциявирусная нагрузкаВПЧ-статусинтеграция ДНК вируса в клеточный геномhuman papillomavirushigh carcinogenic riskcervical cancerHPV genotypemultiple infectionviral loadHPV statusvirus DNA integration into the cell genomeReferencesSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clin. 2021 May;71(3):209–249. https://doi.org/10.3322/caac.21660Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clin. 2021 May;71(3):209–249. https://doi.org/10.3322/caac.21660Злокачественные новообразования в России в 2021 году (заболеваемость и смертность). Под ред. А. Д. Каприна, В. В. Старинского, А. О. Шахзадовой. М.: МНИОИ им. П. А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2022, 252 с. Доступно по: https://oncology-association.ru/wp-content/uploads/2022/11/zlokachestvennye-novoobrazovani- ya-v-rossii-v-2021-g_zabolevaemost-i-smertnost.pdf. Дата обращения: 28.11.2023.Malignant neoplasms in Russia in 2021 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Мoscow: P. Hertsen Moscow Oncology Research Institute– Branchofthe National Medical Radiology Research Centreofthe Ministryof Health of the Russian Federation; 2022, 252 с. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2022/11/zlo- kachestvennye-novoobrazovaniya-v-rossii-v-2021-g_zabolevaemost-i-smertnost.pdf. Accessed: 28.11.2023.Okuma K, Yamashita H, Yokoyama T, Nakagawa K, Kawana K. Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence. Strahlenther Onkol. 2016 Jan;192(1):55–62. https://doi.org/10.1007/s00066-015-0909-0Okuma K, Yamashita H, Yokoyama T, Nakagawa K, Kawana K. Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence. Strahlenther Onkol. 2016 Jan;192(1):55–62. https://doi.org/10.1007/s00066-015-0909-0Bosch FX, Lorincz A, Munoz N, Meijer CJLM, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002 Apr 1;55(4):244–265. https://doi.org/10.1136/jcp.55.4.244Bosch FX, Lorincz A, Munoz N, Meijer CJLM, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002 Apr 1;55(4):244–265. https://doi.org/10.1136/jcp.55.4.244Mkrtchian L, Zamulaeva I, Krikunova L, Kiseleva V, Matchuk O, Liubina L, et al. HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer. J Pers Med. 2021 May 27;11(6):479. https://doi.org/10.3390/jpm11060479Mkrtchian L, Zamulaeva I, Krikunova L, Kiseleva V, Matchuk O, Liubina L, et al. HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer. J Pers Med. 2021 May 27;11(6):479. https://doi.org/10.3390/jpm11060479Rodríguez-Carunchio L, Soveral I, Steenbergen R, Torné A, Martinez S, Fusté P, et al. HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis. BJOG: Int J Obstet Gy. 2015 Jan;122(1):119–127. https://doi.org/10.1111/1471-0528.13071Rodríguez-Carunchio L, Soveral I, Steenbergen R, Torné A, Martinez S, Fusté P, et al. HPV-negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis. BJOG: Int J Obstet Gy. 2015 Jan;122(1):119–127. https://doi.org/10.1111/1471-0528.13071Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 2006 May 1;110(5):525–541. htt ://doi.org/10.1042/cs20050369Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 2006 May 1;110(5):525–541. htt ://doi.org/10.1042/cs20050369Raybould R, Fiander A, Hibbitts S. Human Papillomavirus Integration and its Role in Cervical Malignant Progression. Open Clin Cancer J. 2011 Jan 25;5:1–7. https://doi.org/10.2174/1874189401105010001Raybould R, Fiander A, Hibbitts S. Human Papillomavirus Integration and its Role in Cervical Malignant Progression. Open Clin Cancer J. 2011 Jan 25;5:1–7. https://doi.org/10.2174/1874189401105010001Каприн А. Д., Киселева В. И., Мкртчян Л. С., Замулаева И. А., Шипулина О. Ю., Крикунова Л. И. Способ прогнозирования клинического исхода местно-распространенных форм рака шейки матки. Патент РФ № 2674675. Заявл 07.02.2018; Опубл. 12.12.2018.Kaprin AD, Kiseleva VI, Mkrtchyan LS, Zamulaeva IA, Shipulina OYu, Krikunova LI. A method for predicting the clinical outcome of locally advanced forms of cervical cancer. The patent of the Russian Federation № 2674675. 12.12.2018. (In Russ.).Igidbashian S, Schettino MT, Boveri S, Barberis M, Sandri MT, Carinelli S, et al. Tissue Genotyping of 37 In Situ and Invasive Cervical Cancer With a Concomitant Negative HC2 HPV DNA Test. J Low Genit Tract Dis. 2014 Jan;18(1):87–91. https://doi.org/10.1097/lgt.0b013e3182909f86Igidbashian S, Schettino MT, Boveri S, Barberis M, Sandri MT, Carinelli S, et al. Tissue Genotyping of 37 In Situ and Invasive Cervical Cancer With a Concomitant Negative HC2 HPV DNA Test. J Low Genit Tract Dis. 2014 Jan;18(1):87–91. https://doi.org/10.1097/lgt.0b013e3182909f86Tao X, Zheng B, Yin F, Zeng Z, Li Z, Griffith CC, et al. Polymerase Chain Reaction Human Papillomavirus (HPV) Detection and HPV Genotyping in Invasive Cervical Cancers With Prior Negative HC2 Test Results. Am J Clin Pathol. 2017 May;147(5):477–483. https://doi.org/10.1093/ajcp/aqx027Tao X, Zheng B, Yin F, Zeng Z, Li Z, Griffith CC, et al. Polymerase Chain Reaction Human Papillomavirus (HPV) Detection and HPV Genotyping in Invasive Cervical Cancers With Prior Negative HC2 Test Results. Am J Clin Pathol. 2017 May;147(5):477–483. https://doi.org/10.1093/ajcp/aqx027Chong GO, Lee YH, Han HS, Lee HJ, Park JY, Hong DG, et al. Prognostic value of pretreatment human papilloma virus DNA status in cervical cancer. Gynecol Oncol. 2018 Jan;148(1):97–102. https://doi.org/10.1016/j.ygyno.2017.11.003Chong GO, Lee YH, Han HS, Lee HJ, Park JY, Hong DG, et al. Prognostic value of pretreatment human papilloma virus DNA status in cervical cancer. Gynecol Oncol. 2018 Jan;148(1):97–102. https://doi.org/10.1016/j.ygyno.2017.11.003Datta NR, Kumar P, Singh S, Gupta D, Srivastava A, Dhole TN. Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix? A pilot study. Gynecol Oncol. 2006 Oct;103(1):100–105. https://doi.org/10.1016/j.ygyno.2006.01.058Datta NR, Kumar P, Singh S, Gupta D, Srivastava A, Dhole TN. Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix? A pilot study. Gynecol Oncol. 2006 Oct;103(1):100–105. https://doi.org/10.1016/j.ygyno.2006.01.058WHO/ICO Information Centre on HPV and Cancer. Russian Federation: Human Papillomavirus and Related Cancers, Fact Sheet. 2017, 334 р.WHO/ICO Information Centre on HPV and Cancer. Russian Federation: Human Papillomavirus and Related Cancers, Fact Sheet. 2017, 334 р.Li N, Franceschi S, Howell-Jones R, Snijders PJF, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011 Feb 15;128(4):927–935. https://doi.org/10.1002/ijc.25396Li N, Franceschi S, Howell-Jones R, Snijders PJF, Clifford GM. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011 Feb 15;128(4):927–935. https://doi.org/10.1002/ijc.25396Чуруксаева О. Н. Повышение эффективности лечения больных местнораспространенным раком шейки матки. Дисс. Томск, 2013, 280 с.Churuksaeva ON. Improving the effectiveness of treatment of patients with locally advanced cervical cancer. Diss. Tomsk, 2013, 280 p. (In Russ.).Шипулина О. Ю. Эпидемиологические особенности и меры профилактики онкогинекологической патологии папилломавирусной этиологии. Дисс. М., 2013, 24 с.Shipulina OYu. Epidemiologic features and measures of prevention of oncogynecologic oncogynecologic pathology of papillomavirus etiology. Diss. Мoscow, 2013, 24 p. (In Russ.).Чуруксаева О. Н., Шпилева О. В., Коломиец Л. А., Ибрагимова М. К. Особенности папилломавирусной инфекции у больных с цервикальными неоплазиями и раком шейки матки. Сибирский онкологический журнал. 2015;(S2):57–59.Churuksaeva ON, Shpileva OV, Kolomiets LA, Ibragimova MK. Features of papillomavirus infection in patients with cervical neoplasia and cervical cancer. Siberian Journal of Oncology. 2015;(S2):57–59. (In Russ.).Pirog EC, Lloveras B, Molijn A, Tous S, Guimerà N, Alejo M, et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Mod Pathol. 2014 Dec;27(12):1559–1567. https://doi.org/10.1038/modpathol.2014.55Pirog EC, Lloveras B, Molijn A, Tous S, Guimerà N, Alejo M, et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Mod Pathol. 2014 Dec;27(12):1559–1567. https://doi.org/10.1038/modpathol.2014.55Xing B, Guo J, Sheng Y, Wu G, Zhao Y. Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review. Front Oncol. 2021 Feb 17;10:606335. https://doi.org/10.3389/fonc.2020.606335Xing B, Guo J, Sheng Y, Wu G, Zhao Y. Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review. Front Oncol. 2021 Feb 17;10:606335. https://doi.org/10.3389/fonc.2020.606335Xu X, Feng T, Li D, Lou H, Lan H. Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China. BMC Infect Dis. 2022 Dec 15;22(1):941. https://doi.org/10.1186/s12879-022-07888-0Xu X, Feng T, Li D, Lou H, Lan H. Prevalent distribution and survival outcome of HPV infection in patients with early-stage cervical cancer in Hangzhou, China. BMC Infect Dis. 2022 Dec 15;22(1):941. https://doi.org/10.1186/s12879-022-07888-0Holl K, Nowakowski AM, Powell N, McCluggage WG, Pirog EC, Collas De Souza S, et al. Human papillomavirus prevalence and type distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study. Int J Cancer. 2015 Dec 15;137(12):2858–2868. https://doi.org/10.1002/ijc.29651Holl K, Nowakowski AM, Powell N, McCluggage WG, Pirog EC, Collas De Souza S, et al. Human papillomavirus prevalence and type distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study. Int J Cancer. 2015 Dec 15;137(12):2858–2868. https://doi.org/10.1002/ijc.29651Okonogi N, Kobayashi D, Suga T, Imai T, Wakatsuki M, Ohno T, et al. Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer. Oncol Lett. 2018;15(1):459–466. https://doi.org/10.3892/ol.2017.7327Okonogi N, Kobayashi D, Suga T, Imai T, Wakatsuki M, Ohno T, et al. Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer. Oncol Lett. 2018;15(1):459–466. https://doi.org/10.3892/ol.2017.7327Lan Z, Zhang J, Li H, He R, Zhao Q, Yang F. Prevalence of human papillomavirus genotypes and related cervical morphological results in southern Hunan Province of China, 2018–2020: Baseline measures at a tertiary institution prior to mass human papillomavirus vaccination. Front Microbiol. 2023 Jan 4;13:1094560. https://doi.org/10.3389/fmicb.2022.1094560Lan Z, Zhang J, Li H, He R, Zhao Q, Yang F. Prevalence of human papillomavirus genotypes and related cervical morphological results in southern Hunan Province of China, 2018–2020: Baseline measures at a tertiary institution prior to mass human papillomavirus vaccination. Front Microbiol. 2023 Jan 4;13:1094560. https://doi.org/10.3389/fmicb.2022.1094560Mastutik G, Rahniayu A, Kurniasari N, Rahaju AS, Harjanto B. Distribution of Human Papilloma Virus (HPV) in Cervical Adenocarcinoma and Adenosquamous Carcinoma. Fol Med Indones. 2021 Jun 1;57(2):170. https://doi.org/10.20473/fmi.v57i2.26473Mastutik G, Rahniayu A, Kurniasari N, Rahaju AS, Harjanto B. Distribution of Human Papilloma Virus (HPV) in Cervical Adenocarcinoma and Adenosquamous Carcinoma. Fol Med Indones. 2021 Jun 1;57(2):170. https://doi.org/10.20473/fmi.v57i2.26473Chen Z, Zhou J, Chen Y, Zhu J. Distribution of human papillomavirus genotypes and its relationship to clinicopathology in invasive cervical carcinoma in Zhejiang Province, China. J Cancer Res Ther. 2018;14(4):780–784. https://doi.org/10.4103/0973-1482.231428Chen Z, Zhou J, Chen Y, Zhu J. Distribution of human papillomavirus genotypes and its relationship to clinicopathology in invasive cervical carcinoma in Zhejiang Province, China. J Cancer Res Ther. 2018;14(4):780–784. https://doi.org/10.4103/0973-1482.231428Zhang L, Bi Q, Deng H, Xu J, Chen J, Zhang M, Mu X. Human papillomavirus infections among women with cervical lesions and cervical cancer in Eastern China: genotype-specific prevalence and attribution. BMC Infect Dis. 2017 Dec;17(1):107. https://doi.org/10.1186/s12879-017-2223-1Zhang L, Bi Q, Deng H, Xu J, Chen J, Zhang M, Mu X. Human papillomavirus infections among women with cervical lesions and cervical cancer in Eastern China: genotype-specific prevalence and attribution. BMC Infect Dis. 2017 Dec;17(1):107. https://doi.org/10.1186/s12879-017-2223-1Мкртчян Л. С., Замулаева И. А., Киселева В. И. и др. Рак шейки матки: химиолучевая терапия и прогностическая роль вируса папилломы человека. Под ред. Иванова С. А., Каприна А. Д. М.: ГЕОС; 2022, 188 с.Mkrtchyan LS, Zamulaeva IA, Kiseleva VI, et al. Cervical cancer: chemoradiotherapy and the prognostic role of human papillomavirus. Edited by Ivanov SA, Kaprin AD. Мoscow: “GEOS” Publ.; 2022, 188 p. (In Russ.).Kaliff M, Sorbe B, Mordhorst LB, Helenius G, Karlsson MG, Lillsunde-Larsson G. Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy. Oncotarget. 2018 Apr 10;9(27):18786–18796. https://doi.org/10.18632/oncotarget.2466Kaliff M, Sorbe B, Mordhorst LB, Helenius G, Karlsson MG, Lillsunde-Larsson G. Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy. Oncotarget. 2018 Apr 10;9(27):18786–18796. https://doi.org/10.18632/oncotarget.2466Евстигнеева Л. А., Бахидзе Е. В., Семиглазов В. В. и др. Роль вирусологических факторов в развитии рака шейки матки у молодых женщин. Журнал акушерства и женских болезней. 2007;57:153–154.Evstigneeva LA, Bakhidze EV, Semiglazov VV, et al. The role of virologic factors in the development of cervical cancer in young women. Journal of Obstetrics and Women’s Diseases. 2007;57:153–154. (In Russ.).Carvalho NDO, Del Castillo DM, Perone C, Januário JN, Melo VHD, Brasileiro Filho G. Comparison of HPV genotyping by type-specific PCR and sequencing. Mem Inst Oswaldo Cruz. 2010 Feb;105(1):73–78. https://doi.org/10.1590/s0074-02762010000100011Carvalho NDO, Del Castillo DM, Perone C, Januário JN, Melo VHD, Brasileiro Filho G. Comparison of HPV genotyping by type-specific PCR and sequencing. Mem Inst Oswaldo Cruz. 2010 Feb;105(1):73–78. https://doi.org/10.1590/s0074-02762010000100011Евстигнеева Л. А. Вирусологические и клинико-иммунологические особенности плоскоклеточного рака шейки матки. Дисс. СПб., 2008, 22 с.Evstigneeva LA. Virologic and clinical and immunologic features of squamous cell carcinoma of the cervix. Diss. St. Petersburg, 2008, 22 p. (In Russ.).Шипицина Е. В., Оржесковская Е. А., Бабкина К. А., Савичева А. М., Орлова О. О., Юркова И. К., и др. Определение вирусной нагрузки и статуса ДНК вируса папилломы человека 16 типа методом ПЦР в реальном времени. Журнал акушерства и женских болезней. 2004;53(4):26–32.Shipitsyna EV, Orzheskovskaya EA, Babkina KA, Savicheva AM, Mikaya NA, Orlova OO, Yurkova IK. Determination of viral load and state of human papillomavirus type 16 using real-time PCR. Journal of Obstetrics and Women’s Diseases. 2004;53(4):26–32. (In Russ.).Oyervides-Muñoz MA, Pérez-Maya AA, Sánchez-Domínguez CN, Berlanga-Garza A, Antonio-Macedo M, Valdéz-Chapa LD, et al. Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women. Viruses. 2020 Mar 31;12(4):380. htt ://doi.org/10.3390/v12040380Oyervides-Muñoz MA, Pérez-Maya AA, Sánchez-Domínguez CN, Berlanga-Garza A, Antonio-Macedo M, Valdéz-Chapa LD, et al. Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women. Viruses. 2020 Mar 31;12(4):380. htt ://doi.org/10.3390/v12040380Senapati R, Nayak B, Kar SK, Dwibedi B. HPV Genotypes distribution in Indian women with and without cervical carcinoma: Implication for HPV vaccination program in Odisha, Eastern India. BMC Infect Dis. 2017 Jan 5;17(1):30. https://doi.org/10.1186/s12879-016-2136-4Senapati R, Nayak B, Kar SK, Dwibedi B. HPV Genotypes distribution in Indian women with and without cervical carcinoma: Implication for HPV vaccination program in Odisha, Eastern India. BMC Infect Dis. 2017 Jan 5;17(1):30. https://doi.org/10.1186/s12879-016-2136-4Shukla S, Mahata S, Shishodia G, Pande S, Verma G, Hedau S, et al. Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer. Indian J Med Res. 2014 Apr;139(4):531-43.Shukla S, Mahata S, Shishodia G, Pande S, Verma G, Hedau S, et al. Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer. Indian J Med Res. 2014 Apr;139(4):531-43.Li Y, Wang H, Zhang Y, Jing X, Wu N, Hou Y, Hao C. Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade. Int J Gynaecol Obstet. 2021 Jan;152(1):96–102. https://doi.org/10.1002/ijgo.13406Li Y, Wang H, Zhang Y, Jing X, Wu N, Hou Y, Hao C. Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade. Int J Gynaecol Obstet. 2021 Jan;152(1):96–102. https://doi.org/10.1002/ijgo.13406De Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol. 2018 Feb;47:2–13. https://doi.org/10.1016/j.bpobgyn.2017.08.015De Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol. 2018 Feb;47:2–13. https://doi.org/10.1016/j.bpobgyn.2017.08.015Del Río-Ospina L, Soto-De León SC, Camargo M, Moreno-Pérez DA, Sánchez R, Pérez-Prados A, et al. The DNA load of six high-risk human papillomavirus types and its association with cervical lesions. BMC Cancer. 2015 Dec;15(1):100. https://doi.org/10.1186/s12885-015-1126-zDel Río-Ospina L, Soto-De León SC, Camargo M, Moreno-Pérez DA, Sánchez R, Pérez-Prados A, et al. The DNA load of six high-risk human papillomavirus types and its association with cervical lesions. BMC Cancer. 2015 Dec;15(1):100. https://doi.org/10.1186/s12885-015-1126-zWang W, Zhang XH, Li M, Hao CH, Zhao ZM, Liang HP. Association between viral loads of different oncogenic human papillomavirus types and the degree of cervical lesions in the progression of cervical Cancer. Clin Chim Acta. 2018 Aug;483:249-255. https://doi.org/10.1016/j.cca.2018.05.016Wang W, Zhang XH, Li M, Hao CH, Zhao ZM, Liang HP. Association between viral loads of different oncogenic human papillomavirus types and the degree of cervical lesions in the progression of cervical Cancer. Clin Chim Acta. 2018 Aug;483:249-255. https://doi.org/10.1016/j.cca.2018.05.016Ибрагимова М. К., Цыганов М. М., Карабут И. В., Чуруксаева О. Н., Шпилева О. Н., Бычков В. А., и др. Интегративная и эписомальная формы генотипа 16 вируса папилломы человека при цервикальных интраэпителиальных неоплазиях и раке шейки матки. Вопросы вирусологии. 2016;61(6):270–274. https://doi.org/10.18821/0507-4088-2016-61-6-270-274Ibragimova MK, Tsyganov MM, Karabut IV, Churuksaeva ON, Shpileva ON, Bychkov VA, et al. Integrative and episomal forms of genotype 16 of human papillomavirus in patients with cervical intraepithelial neoplasia and cervical cancer. Problems of Virology, Russian Journal. 2016;61(6):270–274. (In Russ.). https://doi.org/10.18821/0507-4088-2016-61-6-270-274Deng T, Feng Y, Zheng J, Huang Q, Liu J. Low initial human papillomavirus viral load may indicate worse prognosis in patients with cervical carcinoma treated with surgery. J Gynecol Oncol. 2015;26(2):111. https://doi.org/10.3802/jgo.2015.26.2.111Deng T, Feng Y, Zheng J, Huang Q, Liu J. Low initial human papillomavirus viral load may indicate worse prognosis in patients with cervical carcinoma treated with surgery. J Gynecol Oncol. 2015;26(2):111. https://doi.org/10.3802/jgo.2015.26.2.111Zuo J, Huang Y, An J, Yang X, Li N, Huang M, Wu L. Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a long-term follow-up. Chin J Cancer Res. 2019;31(2):389–399. http://doi.org/10.21147/j.issn.1000-9604.2019.02.13Zuo J, Huang Y, An J, Yang X, Li N, Huang M, Wu L. Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a long-term follow-up. Chin J Cancer Res. 2019;31(2):389–399. http://doi.org/10.21147/j.issn.1000-9604.2019.02.13Raybould R., Fiander A., Hibbitts S. Human Papillomavirus Integration and its Role in Cervical Malignant Progression. Open Clin Cancer J. 2011;5:1–7. https://doi.org/10.2174/1874189401105010001Raybould R., Fiander A., Hibbitts S. Human Papillomavirus Integration and its Role in Cervical Malignant Progression. Open Clin Cancer J. 2011;5:1–7. https://doi.org/10.2174/1874189401105010001Li W, Wang W, Si M, Han L, Gao Q, Luo A, et al. The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma. J Cancer Res Clin Oncol. 2008 Dec;134(12):1355–1361. https://doi.org/10.1007/s00432-008-0413-3Li W, Wang W, Si M, Han L, Gao Q, Luo A, et al. The physical state of HPV16 infection and its clinical significance in cancer precursor lesion and cervical carcinoma. J Cancer Res Clin Oncol. 2008 Dec;134(12):1355–1361. https://doi.org/10.1007/s00432-008-0413-3Manawapat-Klopfer A, Wang L, Haedicke-Jarboui J, Stubenrauch F, Munk C, Thomsen LT, et al. HPV16 viral load and physical state measurement as a potential immediate triage strategy for HR-HPV-infected women: a study in 644 women with single HPV16 infections. Am J Cancer Res. 2018 Apr 1;8(4):715–722.Manawapat-Klopfer A, Wang L, Haedicke-Jarboui J, Stubenrauch F, Munk C, Thomsen LT, et al. HPV16 viral load and physical state measurement as a potential immediate triage strategy for HR-HPV-infected women: a study in 644 women with single HPV16 infections. Am J Cancer Res. 2018 Apr 1;8(4):715–722.Chang L, He X, Yu G, Wu Y. Effectiveness of HPV 16 viral load and the E2/E6 ratio for the prediction of cervical cancer risk among Chinese women J Med Virol. 2013.85(4):646–654. https://doi.org/10.1002/jmv.23490Chang L, He X, Yu G, Wu Y. Effectiveness of HPV 16 viral load and the E2/E6 ratio for the prediction of cervical cancer risk among Chinese women J Med Virol. 2013.85(4):646–654. https://doi.org/10.1002/jmv.23490Kahla S, Kochbati L, Badis Chanoufi M, Maalej M, Oueslati R. HPV-16 E2 Physical Status and Molecular Evolution in Vivo in Cervical Carcinomas. Int J Biol Markers. 2014 Jan;29(1):e78–e85. https://doi.org/10.5301/jbm.5000051Kahla S, Kochbati L, Badis Chanoufi M, Maalej M, Oueslati R. HPV-16 E2 Physical Status and Molecular Evolution in Vivo in Cervical Carcinomas. Int J Biol Markers. 2014 Jan;29(1):e78–e85. https://doi.org/10.5301/jbm.5000051Золотоверхая Е. А. Молекулярные маркеры онкогенной активности вируса папилломы человека. Дисс. СПб., 2009, 25 с.Zolotoverkhaya EA. Molecular markers of human papillomavirus oncogenic activity. Diss. St. Petersburg, 2009, 25 p. (In Russ.).Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T. Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev. 2009;10(3):355–360.Nambaru L, Meenakumari B, Swaminathan R, Rajkumar T. Prognostic significance of HPV physical status and integration sites in cervical cancer. Asian Pac J Cancer Prev. 2009;10(3):355–360.De Boer MA, Jordanova ES, Kenter GG, Peters AA, Corver WE, Trimbos JB, Fleuren GJ. High Human Papillomavirus Oncogene mRNA Expression and Not Viral DNA Load Is Associated with Poor Prognosis in Cervical Cancer Patients. Clinical Cancer Research. 2007 Jan 1;13(1):132–138. https://doi.org/10.1158/1078-0432.ccr-06-1568De Boer MA, Jordanova ES, Kenter GG, Peters AA, Corver WE, Trimbos JB, Fleuren GJ. High Human Papillomavirus Oncogene mRNA Expression and Not Viral DNA Load Is Associated with Poor Prognosis in Cervical Cancer Patients. Clinical Cancer Research. 2007 Jan 1;13(1):132–138. https://doi.org/10.1158/1078-0432.ccr-06-1568Joo J, Omae Y, Hitomi Y, Park B, Shin HJ, Yoon KA, et al. The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immuneor DNA repair-related genes in cervical cancer patients. Sci Rep. 2019 Sep 11;9(1):13132. htt ://doi.org/10.1038/s41598-019-49523-0Joo J, Omae Y, Hitomi Y, Park B, Shin HJ, Yoon KA, et al. The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immuneor DNA repair-related genes in cervical cancer patients. Sci Rep. 2019 Sep 11;9(1):13132. htt ://doi.org/10.1038/s41598-019-49523-0Huang SS, Hao DZ, Zhang Y, Liu HM, Shan WS. Progress in studies of the mechanisms and clinical diagnosis of cervical carcinoma associated with genomic integration of high-risk human papillomavirus DNA. Yi Chuan. 2017 Sep 20;39(9):775–783.Huang SS, Hao DZ, Zhang Y, Liu HM, Shan WS. Progress in studies of the mechanisms and clinical diagnosis of cervical carcinoma associated with genomic integration of high-risk human papillomavirus DNA. Yi Chuan. 2017 Sep 20;39(9):775–783.Li H, Yang Y, Zhang R, Cai Y, Yang X, Wang Z, et al. Preferential sites for the integration and disruption of human papillomavirus 16 in cervical lesions. J Clin Virol. 2013 Apr;56(4):342–347. https://doi.org/10.1016/j.jcv.2012.12.014Li H, Yang Y, Zhang R, Cai Y, Yang X, Wang Z, et al. Preferential sites for the integration and disruption of human papillomavirus 16 in cervical lesions. J Clin Virol. 2013 Apr;56(4):342–347. https://doi.org/10.1016/j.jcv.2012.12.014Kiseleva VI, Mkrtchyan LS, Ivanov SA, Lyubina LV, Bezyaeva GP, Panarina LV, et al. The Presence of Human Papillomavirus DNA Integration is Associated with Poor Clinical Results in Patients with Third-Stage Cervical Cancer. Bull Exp Biol Med. 2019 Nov;168(1):87–91. https://doi.org/10.1007/s10517-019-04654-2Kiseleva VI, Mkrtchyan LS, Ivanov SA, Lyubina LV, Bezyaeva GP, Panarina LV, et al. The Presence of Human Papillomavirus DNA Integration is Associated with Poor Clinical Results in Patients with Third-Stage Cervical Cancer. Bull Exp Biol Med. 2019 Nov;168(1):87–91. https://doi.org/10.1007/s10517-019-04654-2Moberg M, Gustavsson I, Wilander E, Gyllensten U. High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer. 2005 Mar;92(5):891–894. https://doi.org/10.1038/sj.bjc.6602436Moberg M, Gustavsson I, Wilander E, Gyllensten U. High viral loads of human papillomavirus predict risk of invasive cervical carcinoma. Br J Cancer. 2005 Mar;92(5):891–894. https://doi.org/10.1038/sj.bjc.6602436Киселева В. И., Крикунова Л. И., Любина Л. В., Мкртчян Л. С., Безяева Г. П., Панарина Л. В., и др. Количественная нагрузка вируса папилломы человека 16 типа и прогнозирование эффективности лечения рака шейки матки. Радиация и риск. 2011;20(2):58–63.Kiseleva VI, Krikunova LI, Lyubina LV, Mkrtchyan LS, Bezyaeva GP, Panarina LV, et al. Quantitative human papillomavirus type 16 viral load and prognosis of cervical cancer treatment efficiency. Radiation and Risk. 2011;20(2):58–63. (In Russ.).

The authors declare that there are no conflicts of interest present.