Hoppe-Seyler Karin, Mändl Julia, Adrian Svenja, Kuhn Bianca J, Hoppe-Seyler Felix
Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Viral Transformation Mechanisms (F030), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Viruses. 2017 Jul 5;9(7):174. doi: 10.3390/v9070174.
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The expression of the viral / oncogenes plays a key role for HPV-linked oncogenesis. It recently has been found that low oxygen concentrations ("hypoxia"), as present in sub-regions of HPV-positive cancers, strongly affect the interplay between the HPV oncogenes and their transformed host cell. As a result, a state of dormancy is induced in hypoxic HPV-positive cancer cells, which is characterized by a shutdown of viral oncogene expression and a proliferative arrest that can be reversed by reoxygenation. In this review, these findings are put into the context of the current concepts of both HPV-linked carcinogenesis and of the effects of hypoxia on tumor biology. Moreover, we discuss the consequences for the phenotype of HPV-positive cancer cells as well as for their clinical behavior and response towards established and prospective therapeutic strategies.
致癌型人乳头瘤病毒（HPV）是主要的人类致癌物。病毒癌基因的表达在HPV相关的肿瘤发生过程中起关键作用。最近发现，HPV阳性癌症亚区域中存在的低氧浓度（“缺氧”）会强烈影响HPV癌基因与其转化的宿主细胞之间的相互作用。结果，在缺氧的HPV阳性癌细胞中诱导出一种休眠状态，其特征是病毒癌基因表达停止和增殖停滞，而复氧可逆转这种停滞。在本综述中，这些发现被置于HPV相关致癌作用以及缺氧对肿瘤生物学影响的当前概念背景下进行探讨。此外，我们还讨论了对HPV阳性癌细胞表型的影响，以及对其临床行为和对既定及前瞻性治疗策略反应的影响。
