人乳头瘤病毒16型DNA整合对宫颈癌变的影响*

Research of human papillomavirus type 16 DNA integration contributes to cervical carcinogenesis*

摘要:

研究人乳头瘤病毒（HPV）16型DNA在宫颈鳞状细胞癌（SCC）及其癌前病变中的整合状况，探讨其在宫颈癌变中的作用。方法 采用多重聚合酶链反应技术检测428例HPV-16阳性并经组织学证实具有不同程度宫颈病变及正常宫颈上皮女性的宫颈脱落细胞中HPV-16 DNA的整合状况；采用E2/E6的比值作为整合的替代标志物。研究对象分为病例组（354例）包括经组织病理学证实的103例SCC及251例宫颈高级别鳞状上皮内病变（HSIL），对照组（74例）包括34例宫颈低级别鳞状上皮内病变（LSIL）及40例正常宫颈上皮细胞女性。不同程度宫颈病变中HPV-16 DNA整合率的变化采用χ2趋势分析；病毒整合与现患HSIL及SCC风险的优势比（OlR）采用非条件Logistic回归分析。结果 HPV-16 DNA整合率随宫颈病变的加重逐渐升高，从对照组中的6.8%（5/74），升高至HSIL组的29.9%（75/251）及SCC组的68.0%（70/103），3组整合率比较差异有统计学意义（P?<0.05）。经多因素分析调整吸烟状况及合并感染其他高危型HPV后，HPV-16基因组整合与现患HSIL及SCC风险的优势比为OlR=2.30（95% CI：1.62，3.18）。结论 HPV-16 DNA整合发生在病毒感染自然史的早期，病毒整合在宫颈癌变过程中起促进作用。

Abstract:

Objective To explore the integration status of high-risk human papillomavirus (HR-HPV) type 16 DNA in cervical squamous cell cancer (SCC), its precursors (high-grade cervical squamous intraepithelial lesion, HSIL) and the role of virus integration in cervical carcinogenesis. Methods Viral integration was determined by a multiplex polymerase chain reaction (PCR) in 428 HPV type 16-positive cervical scrapings obtained from women with different grades of histologically confirmed cervical lesions or normal cervical epithelia, and the ratios of E2/E6 genes were used as a surrogate for integration. The case patients included 103 women with SCC and 251 HSIL, while the controls included 34 LSIL and 40 normal cervical epithelia. The prevalence of HPV 16 DNA integration in different grades of cervical lesions was analyzed by χ2 trend test. The association of viral integration and the risk of prevalent HSIL or SCC were assessed by unconditional logistic regression. Results The prevalence of HPV-16 DNA integration increased in parallel with the severity of cervical lesions , which increased from 6.8% (5/74) in controls to 29.9% (75/251) in HSIL and 68.0% (70/103) in SCC (P?