tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2021-11-4-39-47tumors-913Research ArticleОБЗОРЫ И АНАЛИТИКАREVIEWS AND ANALYSISОСНОВНЫЕ МОЛЕКУЛЯРНЫЕ МЕХАНИЗМЫ КАНЦЕРОГЕНЕЗА, ИНДУЦИРОВАННОГО ВИРУСОМ ПАПИЛЛОМЫ ЧЕЛОВЕКАMAIN MOLECULAR MECHANISMS OF CARCINOGENESIS INDUCED BY HUMAN PAPILLOMAVIRUSПолатоваД. Ш.PolatovaD.  S.

Джамила Ш. Полатова, д. м. н., научный руководитель отдела опухолей опорно-двигательной системы Республиканского специализированного научно-практического медицинского центра онкологии и радиологии Минздрава Узбекистана; генеральный секретарь Ассоциации онкологов Узбекистана; заведующая кафедры онкологии и медицинской радиологии Ташкентского государственного стоматологического института

Ташкент

Dzhamila Sh. Polatova, MD, PhD, DSc, Scientific Director of the Department of Tumors of the Musculoskeletal System, Republican specialized Scientific and practical Medical Center of Oncology and Radiology; General Secretary of the Association of Oncologists of Uzbekistan; Head of the Department of Oncology and Medical Radiology, Tashkent state dental institute

Tashkent

МадаминовА. Ю.MadaminovA.  Y.

Ахмад Ю. Мадаминов, врач-ординатор отдела опухолей головы и шеи Республиканского специализированного научно-практического медицинского центра онкологии и радиологии Минздрава Узбекистана; научный соискатель кафедры онкологии и медицинской радиологии Ташкентского государственного стоматологического института

Ташкент 

Akhmad Yu. Madaminov, Resident of the Department of Head and Neck Tumors, Republican specialized Scientific and practical Medical Center of Oncology and Radiology; Scientific Applicant of the Department of Oncology and Medical Radiology, Tashkent state dental institute

Tashkent

akhmad.madaminov@inbox.ruРеспубликанский специализированный научно-практический медицинский центр онкологии и радиологии Минздрава Узбекистана; Ташкентский государственный стоматологический институтУзбекистанRepublican specialized Scientific and practical Medical Center of Oncology and Radiology; Tashkent state dental instituteUzbekistan2021291220211143947Copyright © Полатова Д.Ш., Мадаминов А.Ю., 20222022Полатова Д.Ш., Мадаминов А.Ю.Polatova D.S., Madaminov A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/913

Наиболее широко распространенным инфекционным фактором, вызывающим злокачественные новообразования, является вирус папилломы человека (ВПЧ). 16 генотип ВПЧ часто участвует в канцерогенезе плоскоклеточной карциномы ротоглотки, встречаясь в 80% случаев. Вирусные белки E5, E6 и E7 являются основными драйверами, ответственными за инициирование и прогрессирование опухоли за счет стимуляции пролиферации клеток, выживания клеток, ингибирование клеточного апоптоза и модуляции дифференцировки кератиноцитов. Ранний промотор инициируется выше E6 независимо от дифференцировки клетки и синтезирует транскрипты, которые транслируются на ранних этапах жизненного цикла вируса. Поздний промотор запускается в зависимости от дифференцировки клетки и служит сугубо для производства набора транскриптов, которые побуждают трансляцию белков L1 и L2. Во время входа вируса в клетку белок L1 прикрепляется гепарансульфатными протеогликанами (ГСПГ) на внеклеточном матриксе, после чего вирус проникает в клетку путем микропиноцитоза. Взаимодействие с ГСПГ считается начальным контактом, который способствует конформационным изменениям капсида, позволяя облегчить перенос вириона на вторичные рецепторы. Деление клеток играет важную роль в доставке вирусного генома в ядро. ВПЧ перемещается по цитоплазме в просвете транспортных пузырьков, которые зарождаются из комплекса Гольджи, выстраиваются вдоль микротрубочек и передаются в конденсированные хромосомы. Считается, что интеграция генома ВПЧ вносит вклад в онкогенез за счет увеличения экспрессии онкогенов ВПЧ в клетке с помощью различных механизмов, которые способствуют неуправляемой пролиферации клетки, приводящей к значительному повреждению ДНК. Интегрированные транскрипты могут быть более стабильными и онкогенными, чем транскрипты ВПЧ, происходящие из эписомальной ДНК.

The most widespread infectious factors causing malignant neoplasms are human papillomaviruses (HPV). HPV geno‑ type 16 is often involved in the carcinogenesis of oropharyngeal squamous cell carcinoma, which occurs in 80 % of cases. The viral proteins E5, E6, and E7 are the main drivers responsible for the initiation and progression of cancer through the stimulation of cell proliferation, cell survival, inhibition of cell apoptosis and modulation of keratinocyte differentiation. The early promoter is initiated upstream of E6 independently of cell differentiation and synthesizes transcripts that are translated early in the viral life cycle. The launch of the late promoter depends on cell differentiation and activated for production transcripts that induce translation of the L1 and L2 proteins. During the entry of the virus into the cell, the L1 protein attaches to heparan sulfate proteoglycans (HSPG) on the extracellular matrix, after which the virus enters the cell by micropinocytosis. The interaction with HSPG is considered the initial contact that promotes conformational changes in the capsid, allowing the transfer of the virion to the secondary entry receptor. Cell division plays an important role in the delivery of the viral genome to the nucleus. HPV moves through the cytoplasm in the lumen of transport vesicles, which originate from the Golgi complex, line up along microtubules and are transmitted to condensed chromosomes. It is believed that the integration of the HPV genome increases the expression of HPV oncogenes in the cell, which contributes to uncontrolled cell proliferation and significant DNA damage. Integrated transcripts may be more stable and oncogenic than episomal-derived HPV transcripts.

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