遗传 ›› 2017, Vol. 39 ›› Issue (9): 775-783.doi: 10.16288/j.yczz.17-151

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高危型HPV DNA整合导致宫颈癌的作用机制和临床检测进展

黄莎莎1,2,郝登再2,张岩2,刘厚明3,单万水3   

  1. 1 广东医科大学，湛江 524023
    2 博奥生物集团有限公司转化医学研究院，北京102206
    3 深圳市第三人民医院检验科，深圳 518112
  • 收稿日期:2017-04-24 修回日期:2017-07-17 出版日期:2017-09-20 发布日期:2017-10-21
  • 作者简介:黄莎莎, 硕士研究生,专业方向：临床检验诊断学(病原微生物)。E-mail: 570214476@qq.com
  • 基金资助:
    深圳市科技研发资金项目、深圳市生物芯片研究重点实验室项目资助(ZDSYS201504301534057);深圳市三名工程专项基金项目资助

Progress in studies of the mechanisms and clinical diagnosis of cervical carcinoma associated with genomic integration of high-risk human papillomavirus DNA

Shasha Huang1,2,Dengzai Hao2,Yan Zhang2,Houming Liu3,Wanshui Shan3   

  1. 1 Guangdong Medical University, Zhanjiang 524023, China
    2 Capital Corporation Clinical & Translational Science Institute, Beijing 102206, China
    3 Laboratory of Shenzhen Third People’s Hospital, Shenzhen 518112, China
  • Received:2017-04-24 Revised:2017-07-17 Online:2017-09-20 Published:2017-10-21
  • Supported by:
    Supported by Shenzhen Key Laboratory of Biochip(ZDSYS201504301534057);Funds of Shenzhen for Introduced High-Level Medical Team

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摘要：

高危型人乳头瘤病毒(human papillomavirus, HPV)感染是宫颈癌发生发展的必要因素之一。病毒DNA整合到宿主基因组中被认为是导致宫颈癌最重要的病因。高危型HPV DNA整合往往导致其E1和E2区大部分缺失或中断,E6和E7致癌基因过表达,宿主致癌基因激活和抑癌基因失活。目前研究表明高危型HPV整合可作为优质宫颈病变筛查的预测生物标志物,且其检测的有效方法大都基于荧光原位杂交、实时荧光定量PCR和杂交捕获技术结合Sanger测序法等。本文重点阐述了高危型HPV整合导致宫颈癌的主要机制,描述了宫颈病变筛查标志物以及预防性HPV疫苗研发和推广的研究进展,并综述了高危型HPV DNA整合状态的检测方法。

关键词: 宫颈癌, 人乳头瘤病毒, 基因整合, HPV疫苗

Abstract:

High-risk human papillomavirus (hrHPV) has been identified as a key factor in the development of cervical cancer. Integration of viral DNA into the host genome has been postulated as an important etiological event during cervical carcinogenesis. High-risk HPV DNA integration frequently results in either the deletion or interruption of the large fragment of E1 and E2 region and the overexpression of oncogenes E6 and E7 in the viral genome, and the activation of oncogenes and the inactivation of tumor suppressors in host genome. Recent studies have showed that hrHPV integration can be used as a predictive biomarker in high-quality cervical lesion screening. Most effective diagnostic approaches are based on fluorescence in situ hybridization, real-time quantitative PCR and Sanger sequencing of hybrid captured viral DNA. This review highlights the primary mechanisms of hrHPV DNA integration associated with cervical carcinogenesis, illustrates recent advances in predictive biomarkers in cervical lesion screening and the development and popularization of prophylactic HPV vaccines, and summarizes the various methods of detecting hrHPV DNA integration.

Key words: cervical carcinomas, human papillomavirus, virus integration, HPV vaccines