人乳头瘤病毒 (HPV) 整合与 HPV 感染转化为癌症有关，但使用短读长技术很难研究其基因组后果。为了解决与 HPV 整合相关的失调问题，我们对 63 个宫颈癌基因组进行了长读长测序。我们根据 HPV-人类基因组结构确定了六类整合事件。在所有 HPV 整合体（定义为由 HPV 序列桥接的两个 HPV-人类断点）中，24% 在断点之间包含 HPV 的可变拷贝，我们将这种现象称为异源整合。在个体整合事件中，对 HPV 基因组内部和附近的 DNA 甲基化进行分析，揭示了整合体的甲基化状态与其方向和结构之间的关系。在基因组的兆碱基范围内观察到人类表观基因组和邻近基因表达与 HPV 整合等位基因的顺式失调。通过阐明 HPV 整合的结构、表观遗传和等位基因特异性影响，我们深入了解整合 HPV 在宫颈癌中的作用。

Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer, but its genomic consequences have been difficult to study using short-read technologies. To resolve the dysregulation associated with HPV integration, we performed long-read sequencing on 63 cervical cancer genomes. We identified six categories of integration events based on HPV-human genomic structures. Of all HPV integrants, defined as two HPV-human breakpoints bridged by an HPV sequence, 24% contained variable copies of HPV between the breakpoints, a phenomenon we termed heterologous integration. Analysis of DNA methylation within and in proximity to the HPV genome at individual integration events revealed relationships between methylation status of the integrant and its orientation and structure. Dysregulation of the human epigenome and neighboring gene expression in cis with the HPV-integrated allele was observed over megabase-ranges of the genome. By elucidating the structural, epigenetic, and allele-specific impacts of HPV integration, we provide insight into the role of integrated HPV in cervical cancer.