Human papillomaviruses (HPVs), like many other viruses, are able to integrate their genomes into the host cellular genome. This integration can activate viral oncogenes or alter the function of cellular oncogenes and tumor suppressor genes, thereby increasing the likelihood of HPV-associated tumor development. In particular, HPV types 16 and 18 are responsible for over 70% of all cervical, anal, and oropharyngeal cancers worldwide, with rising incidence. Even more, high-resolution mapping of preferred integration sites using LR-Seq technologies offers deep insights into the molecular mechanisms of HPV integration. LR-Seq enables the detection of complex integration patterns, where the viral genome can be replicated and amplified into virus–host concatemers, including events within large structural variations or highly repetitive genomic regions. Furthermore, aligning LR-Seq data to the latest T2T reference genome (hs1) is necessary to provide new information about viral integration in genomic regions that were previously inaccessible, such as centromeres and other structurally complex repeat-rich loci. In this review, we provide insights into HPV genomic integration revealed by LR-Seq technologies, with a particular focus on how the use of the complete T2T reference genome enhances the detection of integration events in previously uncharacterized, repeat-rich regions of the human genome.
人乳头瘤病毒（HPV）与许多其他病毒一样，能够将其基因组整合到宿主细胞基因组中。这种整合可激活病毒癌基因或改变细胞癌基因及肿瘤抑制基因的功能，从而增加HPV相关肿瘤发生的可能性。特别是HPV 16型和18型，在全球范围内导致了超过70%的宫颈癌、肛门癌和口咽癌，且发病率呈上升趋势。更值得注意的是，利用LR-Seq技术对偏好整合位点进行高分辨率定位，为HPV整合的分子机制提供了深入见解。LR-Seq能够检测复杂的整合模式，其中病毒基因组可被复制并扩增为病毒-宿主串联体，包括发生在大型结构变异或高度重复基因组区域内的整合事件。此外，将LR-Seq数据与最新的T2T参考基因组（hs1）进行比对，对于获取病毒在以往难以研究的基因组区域（如着丝粒和其他结构复杂、富含重复序列的基因座）中的整合新信息至关重要。本综述深入探讨了LR-Seq技术揭示的HPV基因组整合机制，特别关注完整T2T参考基因组如何增强对人类基因组中先前未表征的富含重复序列区域内整合事件的检测能力。
肿瘤(癌症)患者之家