宫颈癌是严重威胁我国妇女生命健康的重大疾病之一。已证实高危型人乳头瘤病毒（Human Papillomavirus，HPV）是宫颈癌的致病因素。宿主核心遗传易感位点变异是关键内在因素，而高危型HPV持续性感染是发病的关键因素和必然条件。我们前期研究证实宫颈癌宿主存在遗传易感变异位点，在宫颈癌演变过程中高危型HPV致癌基因整合到易感宿主DNA，引导宫颈细胞产生基因组不稳定性等分子事件是宫颈癌发生发展的基础。本项目在前期笃实的研究基础上，分析HPV四维空间和超微构象改变，探索高危型HPV特有分子结构性状；另一方面，通过对遗传易感致病基因的精细定位及功能分析，阐明高危型HPV非同源整合模式介导的融合基因特异性结构变异，筛选验证特异表达的融合基因谱，进一步解析宿主癌基因/抑癌基因失衡机制，为深入系统地明确宫颈癌发病机制、建立针对高危型HPV持续性感染及转归的精准靶向干预及早期防治的新策略奠定基础。

Cervical cancer is one of the serious diseases threatening the life and health of Chinese women. High-risk human papillomavirus (HPV) has been demonstrated to be a risk factor of cervical cancer. The mutation of host core genetic susceptibility loci is a critical internal cause, and high-risk HPV persistent infection is the key factor and necessary condition of the disease. Our preliminary studies showed that there are mutated genetic susceptibility loci in cervical cancer patients, in cervical carcinogenesis high-risk HPV oncogene homologous integrate into the genome of susceptible hosts, inducing molecular events such as genomic instability in cervical cells, which is the basis of cervical cancer carcinogenesis and development. On the basis of reliable preliminary studies, the change of HPV four-dimensional space and superfine conformation will be analyzed in this project, and the specific molecular structure characteristics of high-risk HPV will be explored. On the other hand, high-risk HPV nonhomologous integration mode-mediated fusion gene specific structural variation will be illuminated through fine mapping and functional analysis of genetic susceptibility gene, the specific expressed fusion gene profiles will be filtrated and verified for the further analysis the mechanism of host oncogene/anti-oncogene imbalance. The foundation will be laid at illuminating cervical cancer pathogenesis deeply and systematically and establishing precise targeted intervention and early prevention and treatment strategy focusing on high-risk HPV persistent infection and prognosis.