Biological and clinical aspects of HPV-related cancers.
Biological and clinical aspects of HPV-related cancers.
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HPV相关癌症的生物学和临床方面。
DOI：
10.20892/j.issn.2095-3941.2020.0370
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发表时间：
2020-11-15
影响因子：
5.5
通讯作者：
Chen J
中科院分区：
文献类型：
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作者：
Szymonowicz KA;Chen J
癌症相关疾病是全球第二大死亡原因。人乳头状瘤病毒（HPV）是一种主要通过性传播的传染性病原体，可导致男性和女性的HPV相关癌症。几乎所有的宫颈癌都与HPV相关，然而，越来越多的头颈癌（HNC），特别是口咽癌，可能与HPV感染有关。此外，肛门生殖器癌，包括阴道癌、外阴癌、阴茎癌和肛门癌，代表HPV相关癌症的一个子集。虽然宫颈癌的检测和预防在过去几十年中有了显着改善，但肛门生殖器癌仍然难以确认。目前的临床试验包括HPV相关癌症患者，重点是为所有HPV相关癌症找到适当的检测方法，并改进目前应用的治疗方法。HPV病毒癌蛋白E6和E7分别导致p53和pRb的降解，导致进入S期而没有G1停滞。这些高危HPV病毒致癌基因改变许多细胞过程，包括DNA修复、血管生成和/或凋亡，最终导致致癌。此外，对HPV阴性和HPV阳性HNC癌症中一组DNA双链断裂（DSB）修复基因的基因表达和改变的综合分析揭示了这些癌症中DNA修复过程的HPV依赖性修饰的差异。在这篇综述中，我们讨论了HPV相关癌症的现有知识，目前的筛查和治疗方案，以及HPV感染和临床试验的DNA损伤反应相关的生物学方面。
Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.