Human papillomaviruses (HPV) are the causative agents of cervical and other anogenital cancers as well as those of the oropharynx. HPV proteins activate host DNA damage repair factors to promote their viral life cycle in stratified epithelia. Activation of both the ATR pathway and the ATM pathway are essential for viral replication and differentiation-dependent genome amplification. These pathways are also important for maintaining host genomic integrity and their dysregulation or mutation is often seen in human cancers. The APOBEC3 family of cytidine deaminases are innate immune factors that are increased in HPV positive cells leading to the accumulation of TpC mutations in cellular DNAs that contribute to malignant progression. The activation of DNA damage repair factors may corelate with expression of APOBEC3 in HPV positive cells. These pathways may actively drive tumor development implicating/suggesting DNA damage repair factors and APOBEC3 as possible therapeutic targets.

中文翻译：

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人乳头瘤病毒诱导的基因组不稳定性和 DNA 损伤修复途径

人乳头瘤病毒 (HPV) 是宫颈癌和其他肛门生殖器癌以及口咽癌的病原体。HPV 蛋白激活宿主 DNA 损伤修复因子以促进其在分层上皮细胞中的病毒生命周期。ATR 通路和 ATM 通路的激活对于病毒复制和分化依赖性基因组扩增都是必不可少的。这些通路对于维持宿主基因组的完整性也很重要，它们的失调或突变在人类癌症中很常见。APOBEC3 胞苷脱氨酶家族是先天免疫因子，在 HPV 阳性细胞中增加，导致细胞 DNA 中 TpC 突变的积累，从而导致恶性进展。DNA损伤修复因子的激活可能与HPV阳性细胞中APOBEC3的表达相关。