Porter Vanessa L, Marra Marco A
Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Cancers (Basel). 2022 Sep 23;14(19):4623. doi: 10.3390/cancers14194623.
Human papillomavirus (HPV) is the causative driver of cervical cancer and a contributing risk factor of head and neck cancer and several anogenital cancers. HPV's ability to induce genome instability contributes to its oncogenicity. HPV genes can induce genome instability in several ways, including modulating the cell cycle to favour proliferation, interacting with DNA damage repair pathways to bring high-fidelity repair pathways to viral episomes and away from the host genome, inducing DNA-damaging oxidative stress, and altering the length of telomeres. In addition, the presence of a chronic viral infection can lead to immune responses that also cause genome instability of the infected tissue. The HPV genome can become integrated into the host genome during HPV-induced tumorigenesis. Viral integration requires double-stranded breaks on the DNA; therefore, regions around the integration event are prone to structural alterations and themselves are targets of genome instability. In this review, we present the mechanisms by which HPV-dependent and -independent genome instability is initiated and maintained in HPV-driven cancers, both across the genome and at regions of HPV integration.
人乳头瘤病毒（HPV）是宫颈癌的致病驱动因素，也是头颈癌和几种肛门生殖器癌的促成风险因素。HPV诱导基因组不稳定的能力有助于其致癌性。HPV基因可通过多种方式诱导基因组不稳定，包括调节细胞周期以促进增殖、与DNA损伤修复途径相互作用，使高保真修复途径作用于病毒附加体而远离宿主基因组、诱导DNA损伤性氧化应激以及改变端粒长度。此外，慢性病毒感染的存在可导致免疫反应，这也会引起受感染组织的基因组不稳定。在HPV诱导的肿瘤发生过程中，HPV基因组可整合到宿主基因组中。病毒整合需要DNA上的双链断裂；因此，整合事件周围的区域容易发生结构改变，其本身就是基因组不稳定的靶点。在这篇综述中，我们阐述了在HPV驱动的癌症中，HPV依赖性和非依赖性基因组不稳定在全基因组以及HPV整合区域启动和维持的机制。
