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人乳头瘤病毒相关头颈部癌的病理学:特定肿瘤标志物开发的最新数据与前景

Pathology of HPV-Associated Head and Neck Carcinomas: Recent Data and Perspectives for the Development of Specific Tumor Markers.

作者信息

Sastre-Garau Xavier, Harlé Alexandre

机构信息

Service de Pathologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France.

Université de Lorraine, CNRS UMR7039 CRAN, service de Biopathologie, Institut de Cancérologie de Lorraine, Vandoeuvre-Lès-Nancy, France.

出版信息

Front Oncol. 2020 Nov 16;10:528957. doi: 10.3389/fonc.2020.528957. eCollection 2020.

Abstract

A significant subset of carcinomas developed in the head and neck (H&NCs) are associated with specific human papillomaviruses (HPV) genotypes. In particular, 40-60% of oropharyngeal carcinoma cases are linked to HPV. Epidemiological studies have demonstrated that HPV oral infections are predominantly sexually transmitted and are more frequent among men (10-18%) than women (3.6-8.8%). Although there is a large diversity of HPV genotypes associated with H&NCs, HPV16 lineage represents 83% of the reported cases. The prognostic value of HPV as a biological parameter is well recognized. However, the use of HPV DNA as a diagnostic and/or predictive marker is not fully developed. Recent data reporting the physical state of the HPV genome in tumors have shown that HPV DNA integration into the tumor cell genome could lead to the alteration of cellular genes implicated in oncogenesis. Most importantly, HPV DNA corresponds to a tumor marker that can be detected in the blood of patients. Profile of the HPV DNA molecular patterns in tumor cells using New Genome Sequencing-based technologies, allows the identification of highly specific tumor markers valuable for the development of innovative diagnostic and therapeutic approaches. This review will summarize recent epidemiological data concerning HPV-associated H&NCs, the genomic characterization of these tumors, including the presence of HPV DNA in tumor cells, and will propose perspectives for developing improved care of patients with HPV-associated H&NCs, based on the use of viral sequences as personalized tumor markers and, over the longer term, as a therapeutic target.

摘要

头颈部癌(H&NCs)中有很大一部分与特定的人乳头瘤病毒(HPV)基因型相关。特别是,40%-60%的口咽癌病例与HPV有关。流行病学研究表明,HPV口腔感染主要通过性传播,男性(10%-18%)的感染率高于女性(3.6%-8.8%)。尽管与H&NCs相关的HPV基因型种类繁多,但在报告的病例中,HPV16谱系占83%。HPV作为一种生物学参数的预后价值已得到充分认可。然而,将HPV DNA用作诊断和/或预测标志物的应用尚未得到充分发展。最近报告肿瘤中HPV基因组物理状态的数据表明,HPV DNA整合到肿瘤细胞基因组中可能导致参与肿瘤发生的细胞基因发生改变。最重要的是,HPV DNA相当于一种可在患者血液中检测到的肿瘤标志物。利用基于新基因组测序的技术分析肿瘤细胞中HPV DNA的分子模式,能够识别出高度特异性的肿瘤标志物,这些标志物对于开发创新的诊断和治疗方法具有重要价值。本综述将总结近期有关HPV相关H&NCs的流行病学数据、这些肿瘤的基因组特征,包括肿瘤细胞中HPV DNA的存在情况,并将基于将病毒序列用作个性化肿瘤标志物以及从长远来看用作治疗靶点,提出改善HPV相关H&NCs患者护理水平的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f607/7701329/d867cef295f9/fonc-10-528957-g001.jpg

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