The DDR is a complex signaling network responsible for the preservation of genomic integrity. Beta human papillomaviruses (β-HPVs) are able to destabilize the host genome by attenuating the DDR machinery at the molecular scale following expression of the oncogenes E6 and E7. In the event of β-HPV infection, the E6- and E7-mediated inhibition of the DDR enhances the oncogenicity of UV-induced mutations to enable carcinogenesis in an otherwise immunocompetent host, marking an important mechanistic divergence from the alpha genus of HPVs. In this review, we summarize recent updates to build upon the ‘hit-and-run’ hypothesis of β-HPV pathomechanism and highlight strain-dependent variations. Simultaneously, we illuminate points within the β-HPV–DDR interface that may unravel new insights for HPV viral genetics, genus-specific mechanistic models, and developments in targeted molecular therapy of β-HPV-related cancers.

DDR 是一个复杂的信号网络，负责保持基因组的完整性。Beta 人乳头瘤病毒 (β-HPV) 能够通过在致癌基因 E6 和 E7 表达后在分子尺度上减弱 DDR 机制来破坏宿主基因组的稳定性。在 β-HPV 感染的情况下，E6 和 E7 介导的 DDR 抑制增强了紫外线诱导突变的致癌性，从而使具有免疫能力的宿主发生癌变，这标志着与 HPV α 属的重要机制差异。在这篇综述中，我们总结了最近的更新，以建立在 β-HPV 病理机制的“肇事逃逸”假设的基础上，并强调依赖于菌株的变异。同时，我们阐明了 β-HPV-DDR 界面内的点，这些点可能会揭示 HPV 病毒遗传学、属特异性机制模型、