HPV-16 感染和病毒-宿主整合是宫颈癌 (CC) 最重要的危险因素。本研究的目的是开发一种新的分子策略，整合病毒和宿主基因组变异来识别和监测 CC。从公共数据库收集了总共 312 个甲基化和 538 个 RNA-seq 数据集，以识别差异甲基化和表达的基因。使用 ViMIC 数据库分析 HPV 相关病毒整合位点 (VIS)。 2020年9月至2021年8月，对多中心队列回顾性收集的70例HPV-16阳性病例进行HPV-16 E6深度测序和基于PCR的宿主基因（ASTN1、DLX1、ITGA4、RXFP3、SOX17、ZNF671）甲基化检测。在携带 HPV D32E 的 C-33A 细胞系中进行 RNAseq 和表达验证 (NNF671)。采用Lasso和Logistic回归算法构建CC诊断模型。CC患者的平均甲基化水平与肿瘤分期（p = 0.0077）和HPV亚型（p < 0.001）等病理特征呈正相关。 ZNF671 被鉴定为 CC 特异性甲基化标记，具有令人印象深刻的 93% 灵敏度。 HPV-16 D32E 突变和 HPV-16 整合均下调 ZNF671 表达。最后，通过整合 ZNF671 甲基化水平和 HPV E6 突变特征，开发了 CC 诊断列线图，得出了 0.997 的异常 AUC（95% CI：0.934-1.000）。我们的研究表明，HPV 病毒突变与宿主基因表观遗传改变密切相关。抄送。病毒和宿主遗传信息的整合可能是 CC 筛查的一种新的有前景的策略。

HPV-16 infection and viral-host integration are the most important risk factors for cervical cancer (CC). The aim of this study is to develop a new molecular strategy integrated both the viral and host genome variations identifying and monitoring CC.A total of 312 methylation and 538 RNA-seq datasets were collected from public databases to identify differentially methylated and expressed genes. HPV associated virus integration sites (VISs) were analysed using the ViMIC database. From September 2020 to August 2021, the 70 HPV-16 positive cases retrospectively collected from multi-centre cohorts were subjected to HPV-16 E6 deep sequencing and PCR-based host gene (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671) methylation detection. RNAseq and expression validation (NNF671) were performed in C-33A cell line harbouring HPV D32E. Lasso and logistic regression algorithm were used to construct the CC diagnostic model.A positive correlation was observed between the average methylation level of CC patients and their pathological features including tumour stage (p = 0.0077) and HPV subtype (p < 0.001). ZNF671 was identified as a CC-specific methylation marker, with an impressive 93% sensitivity. Both HPV-16 D32E mutation and integration of HPV-16 down-regulated the ZNF671 expression. Finally, a CC diagnostic nomogram was developed by integrating ZNF671 methylation level and HPV E6 mutation feature, yielding an exceptional AUC of 0.997 (95% CI: 0.934-1.000).Our study demonstrated HPV viral mutations are closely related to host gene epigenetic alterations in CC. Integration of the viral and host genetic information might be a new promising strategy for CC screening.