<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">actabiomedica</journal-id><journal-title-group><journal-title xml:lang="ru">Acta Biomedica Scientifica</journal-title><trans-title-group xml:lang="en"><trans-title>Acta Biomedica Scientifica</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2541-9420</issn><issn pub-type="epub">2587-9596</issn><publisher><publisher-name>Scientific Centre for Family Health and Human Reproduction Problems</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29413/ABS.2022-7.2.4</article-id><article-id custom-type="elpub" pub-id-type="custom">actabiomedica-3410</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АКУШЕРСТВО И ГИНЕКОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>OBSTETRICS AND GYNAECOLOGY</subject></subj-group></article-categories><title-group><article-title>Рецидивы рака шейки матки: возможности молекулярной предикции</article-title><trans-title-group xml:lang="en"><trans-title>The recurrences of cervical cancer: Possibilities of molecular prediction</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6396-4948</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ашрафян</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ashrafyan</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, академик РАН, заместитель директора</p><p>117997, г. Москва, ул. Академика Опарина, 4</p></bio><bio xml:lang="en"><p>Dr. Sc. (Med.), Professor, Academician of the Russian Academy of Sciences, Deputy Director</p><p>Oparina str. 4, Moscow 117997</p></bio><email xlink:type="simple">info@oparina4.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5447-4223</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Белокриницкая</surname><given-names>Т. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Belokrinitskaya</surname><given-names>T. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, заведующая кафедрой акушерства и гинекологии педиатрического факультета</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Dr. Sc. (Med.), Professor, Head of the Department of Obstetrics and Gynecology of the Pediatrics Faculty, Faculty of Advanced Training and Professional Retraining</p><p>Gorkogo str. 39А, Chita 672000</p></bio><email xlink:type="simple">tanbell24@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3588-6545</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шолохов</surname><given-names>Л. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Sholokhov</surname><given-names>L. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, заведующий лабораторией физиологии и патологии эндокринной системы</p><p>664003, г. Иркутск, ул. Тимирязева, 16</p></bio><bio xml:lang="en"><p>Dr. Sc. (Med.), Professor, Head of the Laboratory of Physiology and Pathology of the Endocrine System</p><p>Timiryazeva str. 16, Irkutsk 664003</p></bio><email xlink:type="simple">lfshol@mail.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3588-6545</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каюкова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kayukova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук, доцент, заведующая кафедрой онкологии</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Cand. Sc. (Med.), Docent, Head of the Department of Oncology</p><p>Gorkogo str. 39А, Chita 672000</p></bio><email xlink:type="simple">elena_pochta22@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5961-5400</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мудров</surname><given-names>В. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Mudrov</surname><given-names>V. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук, доцент кафедры акушерства и гинекологии лечебного и стоматологического факультетов</p><p>672000, г. Чита, ул. Горького, 39а</p></bio><bio xml:lang="en"><p>Cand. Sc. (Med.), Associate Professor at the Department of Obstetrics and Gynecology of the Faculty of Medicine and Dentistry</p><p>Gorkogo str. 39А, Chita 672000</p></bio><email xlink:type="simple">mudrov_viktor@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Минздрава России</institution></aff><aff xml:lang="en"><institution>National Medical Research Center for Obstetrics, Gynecology&#13;
And Perinatology named after Academician V.I. Kulakov</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Читинская государственная медицинская академия» Минздрава России</institution></aff><aff xml:lang="en"><institution>Chita State Medical Academy</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБНУ «Научный центр проблем здоровья семьи и репродукции человека»</institution></aff><aff xml:lang="en"><institution>Scientific Centre for Family Health and Human Reproduction Problems</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>21</day><month>05</month><year>2022</year></pub-date><volume>7</volume><issue>2</issue><fpage>34</fpage><lpage>41</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ашрафян Л.А., Белокриницкая Т.Е., Шолохов Л.Ф., Каюкова Е.В., Мудров В.А., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Ашрафян Л.А., Белокриницкая Т.Е., Шолохов Л.Ф., Каюкова Е.В., Мудров В.А.</copyright-holder><copyright-holder xml:lang="en">Ashrafyan L.A., Belokrinitskaya T.E., Sholokhov L.F., Kayukova E.V., Mudrov V.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.actabiomedica.ru/jour/article/view/3410">https://www.actabiomedica.ru/jour/article/view/3410</self-uri><abstract><p>Частота возникновения рецидивов рака шейки матки (РШМ) колеблется от 10 до 40 %. Показатель 5-летней выживаемости для больных с рецидивами РШМ составляет около 5–15 % на фоне проводимой современной лекарственной терапии. Известны клинические и морфологические характеристики опухолевого процесса, используемые в качестве маркеров неблагоприятного прогноза развития рецидива РШМ. Поиск молекулярных прогностических маркеров течения РШМ продолжается.</p><sec><title>Цель исследования</title><p>Цель исследования. Определить уровень белков иммунного цикла у больных РШМ 0–IV стадий в зависимости от возникновения рецидива заболевания.</p><p>Материалы и методы исследования. Выполнен ретроспективный анализ ранее полученных результатов исследования по изучению локального уровня белков иммунного цикла у больных РШМ. Спустя 3 года после динамического</p><p>наблюдения были сформированы 2 группы: 1-я группа – больные, леченные от РШМ, без признаков прогрессирования заболевания (n = 83); 2-я группа – больные РШМ с локальным или системным рецидивом (n = 18). Используемые статистические методы: непараметрические методы статистики с применением критерия Краскела – Уоллиса; ROC-анализ для значимых величин с целью расчёта пороговых значений; определение качества выявленных предиктивных маркеров путём расчёта чувствительность, специфичности, точности.</p></sec><sec><title>Результаты исследования</title><p>Результаты исследования. Предиктивным значением для прогнозирования возникновения рецидива РШМ обладают локальные инициальные пороговые величины В7.2 &lt; 10,7 пг/мл (Se = 0,87; Sp = 0,73; Ac = 0,76; AUC = 0,78), PD-L1 ≤ 5,1 пг/мл (Se = 0,87; Sp = 0,68; Ac = 0,71; AUC = 0,76), sCD27 ≥ 32,0 пг/мл (Se = 0,75; Sp = 0,78; Ac = 0,78; AUC = 0,75).</p></sec><sec><title>Заключение</title><p>Заключение. Определение локальных уровней B7.2, PD-L1, sCD27 у больных РШМ до начала лечения можно использовать для прогнозирования развития рецидива заболевания в течение 3 лет наблюдения.</p></sec></abstract><trans-abstract xml:lang="en"><p>The incidence of recurrence of cervical cancer ranges from 10 to 40 %. The 5-year survival rate for patients with recurrent cervical cancer is about 5–15 % against the background of current drug therapy. Clinical and morphological characteristics of the tumor process are known, which are used as markers of an unfavorable prognosis for the development of cervical cancer recurrence. The search for molecular prognostic markers of the course of cervical cancer continues.</p><sec><title>The aim</title><p>The aim. To determine the level of immune cycle proteins in patients with cervical cancer 0–IV stages, depending on the occurrence of a relapse of the disease.</p><p>Materials and research methods. A retrospective analysis of previously obtained results of a study on the local level of immune cycle proteins in patients with cervical cancer was performed. Three years after follow-up, 2 groups were formed: group 1 – patients treated for cervical cancer without signs of disease progression (n = 83); group 2 – patients with cervical cancer with local or systemic recurrence (n = 18). Used statistical methods: non-parametric methods of statistics using the Kruskal – Wallis test; ROC-analysis for significant values in order to calculate threshold values; determination of the quality of the identified predictive markers by calculating the sensitivity, specificity, accuracy.</p></sec><sec><title>Results</title><p>Results. Local initial threshold values have a predictive value for predicting the occurrence of cervical cancer recurrence: B7.2 &lt; 10.7 pg/ml (Se = 0.87; Sp = 0.73; Ac = 0.76; AUC = 0.78), PD-L1 ≤ 5.1 pg/ml (Se = 0.87; Sp = 0.68; Ac = 0.71; AUC = 0.76), sCD27 ≥ 32.0 pg/ml (Se = 0.75; Sp = 0.78; Ac = 0.78; AUC = 0.75).</p></sec><sec><title>Conclusion</title><p>Conclusion. Determination of local levels of B7.2, PD-L1, sCD27 in patients with cervical cancer before treatment can be used to predict the development of disease recurrence during 3 years of follow-up.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>рак шейки матки</kwd><kwd>белки иммунного цикла</kwd><kwd>прогнозирование</kwd><kwd>рецидив</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cervical cancer</kwd><kwd>immune cycle proteins</kwd><kwd>recurrence prediction</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена при финансовой поддержке гранта Президента Российской Федерации для государственной поддержки молодых российских учёных МК-6143.2018.7 (соглашение № 075-02-2018-547). Проведение исследования одобрено Локальным этическим комитетом ФГБОУ ВО «Читинская государственная медицинская академия» Минздрава России (протокол № 44 от 9.11.2012).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Каприн А.Д., Старинский В.В., Шахзадова А.О. Состояние онкологической помощи населению России в 2020 году. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2021.</mixed-citation><mixed-citation xml:lang="en">Kaprin AD, Starinsky VV, Shakhzadova AO. The state of oncological care for the population of Russia in 2020. Moscow; 2021. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Nie H, Bu F, Xu J, Li T, Huang J. 29 immune-related genes pairs signature predict the prognosis of cervical cancer patients. Sci Rep. 2020; 10: 14152. doi: 10.1038/s41598-020-70500-5</mixed-citation><mixed-citation xml:lang="en">Nie H, Bu F, Xu J, Li T, Huang J. 29 immune-related genes pairs signature predict the prognosis of cervical cancer patients. Sci Rep. 2020; 10: 14152. doi: 10.1038/s41598-020-70500-5</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Paik E, Lim MC, Kim MH, Kim YuH, Song ES, Seong JS, et al. Prognostic model for survival and recurrence in patients with early-stage cervical cancer: A Korean Gynecologic Oncology Group study (KGOG 1028). Cancer Res Treat. 2020; 52(1): 320-333. doi: 10.4143/crt.2019.124</mixed-citation><mixed-citation xml:lang="en">Paik E, Lim MC, Kim MH, Kim YuH, Song ES, Seong JS, et al. Prognostic model for survival and recurrence in patients with early-stage cervical cancer: A Korean Gynecologic Oncology Group study (KGOG 1028). Cancer Res Treat. 2020; 52(1): 320-333. doi: 10.4143/crt.2019.124</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Максимов А.Ю., Тимошкова М.Ю., Вереникина Е.В., Лукбанова Е.А., Кечерюкова М.М. Оценка профиля микроРНК в цервикальном эпителии для прогнозирования развития рецидивов рака шейки матки. Альманах клинической медицины. 2020; 48(5): 333-340. doi: 10.18786/2072-0505-2020-48-054</mixed-citation><mixed-citation xml:lang="en">Maksimov AY, Timoshkova MY, Verenikina EV, Lukbanova EA, Kecheryukova MM. Evaluation of microRNA profile in cervical epithelium for predicting cervical cancer recurrence. Almanac of Clinical Medicine. 2020; 48(5): 333-340. (In Russ.). doi: 10.18786/2072-0505-2020-48-054</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Weng Sh, Wu W, Hsiao Y, Yang Sh, Hsu Ch, Wang P. Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer. Int J Med Sci. 2018; 15(12): 1312-1319. doi: 10.7150/ijms.27505</mixed-citation><mixed-citation xml:lang="en">Weng Sh, Wu W, Hsiao Y, Yang Sh, Hsu Ch, Wang P. Significant association of long non-coding RNAs HOTAIR genetic polymorphisms with cancer recurrence and patient survival in patients with uterine cervical cancer. Int J Med Sci. 2018; 15(12): 1312-1319. doi: 10.7150/ijms.27505</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Fu HC, Yang YC, Chen YJ, Lin H, Ou YC, Chien CC, et al. Increased expression of SKP2 is an independent predictor of locoregional recurrence in cervical cancer via promoting DNA-damage response after irradiation. Oncotarget. 2016; 7(28): 44047-44061. doi: 10.18632/oncotarget.10057</mixed-citation><mixed-citation xml:lang="en">Fu HC, Yang YC, Chen YJ, Lin H, Ou YC, Chien CC, et al. Increased expression of SKP2 is an independent predictor of locoregional recurrence in cervical cancer via promoting DNA-damage response after irradiation. Oncotarget. 2016; 7(28): 44047-44061. doi: 10.18632/oncotarget.10057</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Нишанов Д.А., Мамадалиева Я.С., Захирова Н.Н., Каримова Н.С. Прогностическая роль экспрессии молекулярно-генетических маркеров в определении выживаемости больных местнораспространенным раком шейки матки. Онкологический журнал. 2020; 14(4): 79-85.</mixed-citation><mixed-citation xml:lang="en">Nishanov DA, Mamadaliyeva YS, Zakirova NN, Karimova NS. Prognostic role of expression of molecular genetic markers in determining survival in locally advanced cervical cancer. Onkologicheskiy zhurnal. 2020; 14(4): 79-85. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Hu YuX, Zheng MJ, Zhang WCh, Li X, Gou R, Nie X, et al. Systematic profiling of alternative splicing signature reveals prognostic predictor for cervical cancer. J Transl Med. 2019; 17: 379. doi: 10.1186/s12967-019-02140-x</mixed-citation><mixed-citation xml:lang="en">Hu YuX, Zheng MJ, Zhang WCh, Li X, Gou R, Nie X, et al. Systematic profiling of alternative splicing signature reveals prognostic predictor for cervical cancer. J Transl Med. 2019; 17: 379. doi: 10.1186/s12967-019-02140-x</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Yang HJ, Xue JM, Li J, Wan LH, Zhu YuX. Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis. Mol Genet Genomic Med. 2020; 8(6): e1200. doi: 10.1002/mgg3.1200</mixed-citation><mixed-citation xml:lang="en">Yang HJ, Xue JM, Li J, Wan LH, Zhu YuX. Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis. Mol Genet Genomic Med. 2020; 8(6): e1200. doi: 10.1002/mgg3.1200</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Ашрафян Л.А., Белокриницкая Т.Е. Каюкова Е.В., Шолохов Л.Ф., Мудров В.А., Терешков П.П. Локальный уровень белков контрольных точек иммунного цикла у больных раком шейки матки. Забайкальский медицинский вестник. 2021; 4: 11-20. URL: http://zabmedvestnik.ru/arhiv-nomerov/nomer-4-za-2021-god/lokalnyj-uroven-belkov-kontrolnyh-tochek-immunnogocikla-u-bolnyh-rakom-shejki-matki [дата доступа: 01.06.2021].</mixed-citation><mixed-citation xml:lang="en">Ashrafyan LA, Belokrinitskaya TE, Kayukova EV, Sholokhov LF, Mudrov VA, Tereshkov PP. The local level checkpoint proteins of immune cycle in patients with cervical cancer. Transbaikalian Medical Bulletin. 2021; 4: 11-20. (In Russ.). URL: http://zabmedvestnik.ru/arhiv-nomerov/nomer-4-za-2021-god/lokalnyjuroven-belkov-kontrolnyh-tochek-immunnogo-cikla-u-bolnyhrakom-shejki-matki [date of access: 01.06.2021].</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication. Haematologica. 2004; 89(3): 264.</mixed-citation><mixed-citation xml:lang="en">International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication. Haematologica. 2004; 89(3): 264.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Мудров В.А. Алгоритм применения ROC-анализа в биомедицинских исследованиях с помощью пакета программ SPSS. Забайкальский медицинский вестник. 2021; 1: 148-153. URL: http://zabmedvestnik.ru/arhiv-nomerov/nomer-1-za-2021/algoritm-primenenija-roc-analiza-v-biomedicinskihissledovanijah-s-pomoshhju-paketa-programm-spss/975/18.pdf [дата доступа: 01.06.2021].</mixed-citation><mixed-citation xml:lang="en">Mudrov VA. ROC curve analysis algorithm in biomedical research using SPSS software package. Transbaikalian Medical Bulletin. 2021; 1: 148-153. (In Russ.). URL: http://zabmedvestnik.ru/arhiv-nomerov/nomer-1-za-2021/algoritm-primenenija-rocanaliza-v-biomedicinskih-issledovanijah-s-pomoshhju-paketaprogramm-spss/975/18.pdf [date of access: 01.06.2021].</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Nandi D, Pathak S, Verma T, Singh M, Chattopadhyay S, Thakur A, et al. T cell costimulation, checkpoint inhibitors and antitumor therapy. J Biosci. 2020; 45:50.</mixed-citation><mixed-citation xml:lang="en">Nandi D, Pathak S, Verma T, Singh M, Chattopadhyay S, Thakur A, et al. T cell costimulation, checkpoint inhibitors and antitumor therapy. J Biosci. 2020; 45:50.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Heeren A, Punt S, Bleeker M, Gaarenstroom K, van der Velden J, Kenter G, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Modern Pathology. 2016; 29: 753-763. doi: 10.1038/modpathol.2016.64</mixed-citation><mixed-citation xml:lang="en">Heeren A, Punt S, Bleeker M, Gaarenstroom K, van der Velden J, Kenter G, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Modern Pathology. 2016; 29: 753-763. doi: 10.1038/modpathol.2016.64</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Y, Wu L, Tong R, Yang F, Yin L, Li M, et al. PD-1/PD-L1 inhibitors in cervical cancer. Front Pharmacol. 2019; 10: 65. doi: 10.3389/fphar.2019.00065</mixed-citation><mixed-citation xml:lang="en">Liu Y, Wu L, Tong R, Yang F, Yin L, Li M, et al. PD-1/PD-L1 inhibitors in cervical cancer. Front Pharmacol. 2019; 10: 65. doi: 10.3389/fphar.2019.00065</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Minion L, Tewari K. Cervical cancer – State of the science: From angiogenesis blockade to checkpoint inhibition. Gynecol Oncol. 2018: 148(3): 609-621. doi: 10.1016/j.ygyno.2018.01.009</mixed-citation><mixed-citation xml:lang="en">Minion L, Tewari K. Cervical cancer – State of the science: From angiogenesis blockade to checkpoint inhibition. Gynecol Oncol. 2018: 148(3): 609-621. doi: 10.1016/j.ygyno.2018.01.009</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Rotman J, den Otter L, Bleeker M, Samuels S, Heeren A, Roemer M, et al. PD-L1 and PD-L2 expression in cervical cancer: Regulation and biomarker. Front Immunol. 2020; 11: 596825. doi: 10.3389/fimmu.2020.596825</mixed-citation><mixed-citation xml:lang="en">Rotman J, den Otter L, Bleeker M, Samuels S, Heeren A, Roemer M, et al. PD-L1 and PD-L2 expression in cervical cancer: Regulation and biomarker. Front Immunol. 2020; 11: 596825. doi: 10.3389/fimmu.2020.596825</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">O’Neill R, Cao X. Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Adv Cancer Res. 2019; 143: 145-194. doi: 10.1016/bs.acr.2019.03.003</mixed-citation><mixed-citation xml:lang="en">O’Neill R, Cao X. Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Adv Cancer Res. 2019; 143: 145-194. doi: 10.1016/bs.acr.2019.03.003</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
