Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions
Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions
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DOI：
10.1093/jnci/91.11.954
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发表时间：
1999-06-02
期刊：
影响因子：
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通讯作者：
Schiffman, M
中科院分区：
文献类型：
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作者：
Liaw, KL;Glass, AG;Schiffman, M
背景资料：人乳头瘤病毒（HPV）感染与宫颈癌及其细胞学前体鳞状上皮内病变（SIL）密切相关。我们在一组最初细胞学正常的妇女中，前瞻性地研究了在基于聚合酶链反应（PCR）的DNA检测的广泛的生殖器HPV类型后SIL的风险，以阐明HPV在SIL病因学中的作用。研究方法：从1989年4月开始，对在Kaiser Permanente（波特兰，OR）接受常规细胞学筛查的17654名妇女进行了SIL事件发展的随访。在随访期间，380例事件病例患者和1037例匹配的对照受试者有资格参加这项巢式病例对照研究。使用基于PCR的方法检测入组时和随后病例诊断时（或选择中心受试者的相应时间）收集的宫颈灌洗液的HPV DNA。数据以列联表形式进行分析，采用双侧P值，或对于多变量分析，采用比值比（OR）和95%置信区间（CL）。结果如下：与最初HPV阴性的女性相比，在入组时HPV DNA检测阳性的女性在随访期间首次诊断为低度SIL的可能性高3.8倍（95%CI = 2.6-5.5），发展为高度SIL的可能性高12.7倍（95%CI = 6.2-25.9）。在诊断时，HPV DNA与SIL的横断面相关性非常强（低度SIL的OR = 44.4和95%CI = 24.2-81.5，高度SIL的OR = 67.1和95%CI = 19.3-233.7）。HPV 16型是最能预测SIL，甚至是低度SIL的病毒类型。结论：这些发现与HPV感染是宫颈癌的主要原因的假设是一致的，此外，它们支持HPV疫苗研究以预防宫颈癌和开发HPV DNA诊断测试的努力。
Background: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. Methods: Starting in April 1989, 17 654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of central subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CLs). Results: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. Conclusions: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia, Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests.