Abstract

Oral cavity squamous cell carcinoma (OC-SCC) is the most common and aggressive malignancy of the oral cavity. Recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for oral squamous cell carcinoma development, while distinguished role of Epstein-Barr virus (EBV) remains still uncertain. However, the evidence for association between virus infection and risk of oral squamous cell carcinoma is controversially and varies significantly by geographic regions and race. The aim of the present study was to elucidate the prevalence of HPV and EBV in OC-SCC samples of Russian patients from Moscow region. We investigated fresh-frozen tumor tissue fragments obtained from 11 patients with OC-SCC. DNA was extracted and the viral genome was examined by quantitative PCR assays with highrisk type-specific HPV and EBV specific markers followed by sequencing-based analysis. No HPV infection in analyzed OC-SCC samples was observed, while EBV was identified in 70.0% (7/10) of patients. Further based on Q-PCR amplification of the EBV targets including BamHI-W, EBNA1 and C-terminal fragment of LMP1 gene, EBV infection and measurement of virus load in the tumor samples was assessed. Sequencing LMP1-positive products revealed that the most samples (5/6) contained variants LMP1 with Cao deletion characterized by an increased transforming potential. These data suggest that prevalence of EBV infections is common and may influence cancer development, although detected LMP1 variants of EBV are not necessarily associated with the pathogenesis of OC-SCC. Further studies are necessary to determine the potential role of EBV and its possible importance as an infection factor in OC-SCC.

Highlights

  • The aim of the present study was to elucidate the prevalence of human papilloma virus (HPV) and Epstein-Barr virus (EBV) in Oral cavity squamous cell carcinoma (OC-SCC) samples of Russian patients from Moscow region

  • We investigated fresh-frozen tumor tissue fragments obtained from 11 patients with OC-SCC

  • DNA was extracted and the viral genome was examined by quantitative PCR assays with highrisk type-specific HPV and EBV specific markers followed by sequencing-based analysis

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Summary

СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА РОССИЙСКИХ ПАЦИЕНТОВ

Инфицирование вирусом папилломы человека (ВПЧ) является дополнительным фактором риска развития плоскоклеточного рака полости рта, тогда как роль вируса Эпштейна–Барр (ВЭБ) остается невыясненной. Цель: выяснение распространённости ВПЧ и ВЭБ в образцах рака слизистой оболочки ротовой полости пациентов Московского региона России. Экстрагированную ДНК проверяли на наличие вирусных геномов количественной ПЦР-амплификацией с использованием маркёров, специфичных для ВЭБ и высококанцерогенных типов ВПЧ, с последующим секвенированием. Высокая частота вируса в проанализированных образцах позволяет предположить ВЭБ-ассоциированную патологию, хотя обнаруженные LMP1-варианты ВЭБ не обязательно связаны с развитием рака полости рта. Для определения потенциальной роли ВЭБ как инфицирующего агента в патогенезе рака слизистой оболочки полости рта необходимы дальнейшие исследования. Ключевые слова: рак слизистой оболочки полости рта; вирус Эпштейна–Барр; вирус папилломы человека; BamHI-W; EBNA1; LMP1. Выявление геномной ДНК вируса Эпштейна–Барр в тканях рака слизистой оболочки полости рта российских пациентов. Hertzen Moscow Oncology Research Center, Moscow, 125284, Russian Federation; 3Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, 117997, Russian Federation

Introduction
Оригинальные исследования
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Материал и методы
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