Whiteside Martin A, Siegel Erin M, Unger Elizabeth R
Office of Cancer Surveillance, Tennessee Department of Health, Nashville, Tennessee 37243, USA.
Cancer. 2008 Nov 15;113(10 Suppl):2981-94. doi: 10.1002/cncr.23750.
Human papillomaviruses (HPVs) are a major cause of cancer globally, including cervical cancer. The HPV 'early' proteins, E6 and E7, are the chief oncoproteins involved in cancer progression. These oncoproteins are more highly expressed in high-grade dysplasias and invasive cancer coincident with reduced viral DNA replication and reduced production of infective progeny virions. The E6 and E7 oncoproteins interact with several cellular proteins-classically TP53 and RB1, respectively-leading to the degradation of several of these proteins, although all interactions do not necessarily result in the degradation of a cellular protein. HPV infection is also associated with viral and host DNA methylation changes, many of which also occur in cancer types not associated with HPV infection. The E6 and E7 interactions with cellular proteins and DNA methylation changes are associated with changes in the integrity of key cellular pathways that regulate genomic integrity, cell adhesion, the immune response, apoptosis, and cell cycle control. The alterations in key cellular pathways may provide useful biomarkers to improve the sensitivity of current cancer screening methods, such as the Papanicolaou test. This review provides a detailed summary of the interactions of E6 and E7 with cellular proteins and alterations in cellular DNA methylation associated with HPV infection. The importance of molecular biomarkers to the clinical setting, underserved populations, and general public health is discussed.
人乳头瘤病毒（HPV）是全球癌症的主要病因，包括宫颈癌。HPV“早期”蛋白E6和E7是参与癌症进展的主要癌蛋白。这些癌蛋白在高级别发育异常和浸润性癌中表达更高，同时病毒DNA复制减少，感染性子代病毒颗粒产生减少。E6和E7癌蛋白分别与几种细胞蛋白（经典的是TP53和RB1）相互作用，导致其中几种蛋白降解，尽管并非所有相互作用都必然导致细胞蛋白降解。HPV感染还与病毒和宿主DNA甲基化变化有关，其中许多变化也发生在与HPV感染无关的癌症类型中。E6和E7与细胞蛋白的相互作用以及DNA甲基化变化与调节基因组完整性、细胞黏附、免疫反应、细胞凋亡和细胞周期控制的关键细胞通路完整性变化有关。关键细胞通路的改变可能提供有用的生物标志物，以提高当前癌症筛查方法（如巴氏试验）的敏感性。本综述详细总结了E6和E7与细胞蛋白的相互作用以及与HPV感染相关的细胞DNA甲基化变化。讨论了分子生物标志物对临床环境、服务不足人群和公众健康的重要性。
