Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.
Almazov National Medical Research Center, St. Petersburg, 197341, Russia.
Biochemistry (Mosc). 2019 Jul;84(7):782-799. doi: 10.1134/S0006297919070095.
Human papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are eliminated by the immune system. Occasionally, elimination fails, and HPV infection becomes chronic. Replication of HPVs in dividing epithelial cells is accompanied by increased expression of the E6 and E7 oncoproteins. These oncoproteins are responsible for genomic instability, disruption of the cell cycle, cell proliferation, immortalization, and malignant transformation of HPV-infected cells. Besides, E6 and E7 oncoproteins induce immunosuppression, preventing the detection of HPV-infected and transformed cells by the immune system. HPV integration into the genome of the host cell leads to the upregulation of E6 and E7 expression and contributes to HPV-associated malignization. Prophylactic HPV vaccines can prevent over 80% of HPV-associated anogenital cancers. The vaccine elicits immune response that prevents initial infection with a given HPV type but does not eliminate persistent virus once infection has occurred and does not prevent development of the HPV-associated neoplasias, which necessitates the development of therapeutic vaccines to treat chronic HPV infections and HPV-associated malignancies.
人乳头瘤病毒（HPV）感染约占所有癌症的 5%，与所有病原体相关癌症的 30%有关。宫颈癌是全世界女性中第三大常见癌症；约 70%的宫颈癌病例由高危型 HPV（HR HPV）基因型 16 和 18 引起。HPV 感染主要通过性接触发生；然而，病毒也可以通过水平和垂直途径传播。HPV 感染基底角质形成细胞或外-内宫颈移行区细胞后，病毒 DNA 以游离体形式持续存在。在大多数情况下，受感染的细胞被免疫系统消除。偶尔，消除失败，HPV 感染成为慢性。HPV 在分裂上皮细胞中的复制伴随着 E6 和 E7 癌蛋白的表达增加。这些癌蛋白导致基因组不稳定、细胞周期中断、细胞增殖、HPV 感染细胞的永生化和恶性转化。此外，E6 和 E7 癌蛋白诱导免疫抑制，防止免疫系统检测 HPV 感染和转化的细胞。HPV 整合到宿主细胞的基因组中会导致 E6 和 E7 表达上调，并有助于 HPV 相关的恶性转化。预防性 HPV 疫苗可预防 80%以上的 HPV 相关肛门生殖器癌症。疫苗引发免疫反应，可预防特定 HPV 类型的初次感染，但不能消除持续感染的病毒，也不能预防 HPV 相关肿瘤的发展，这就需要开发治疗性疫苗来治疗慢性 HPV 感染和 HPV 相关恶性肿瘤。
