Liaw K L, Glass A G, Manos M M, Greer C E, Scott D R, Sherman M, Burk R D, Kurman R J, Wacholder S, Rush B B, Cadell D M, Lawler P, Tabor D, Schiffman M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
J Natl Cancer Inst. 1999 Jun 2;91(11):954-60. doi: 10.1093/jnci/91.11.954.
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.
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 control 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 (CIs).
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.
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.
人乳头瘤病毒（HPV）感染与宫颈癌及其细胞学前驱病变，即鳞状上皮内病变（SIL）密切相关。我们对一组最初细胞学检查正常的女性进行了前瞻性研究，通过基于聚合酶链反应（PCR）的DNA检测来检测多种生殖道HPV类型，以明确HPV在SIL病因学中的作用。
从1989年4月开始，对在凯撒医疗机构（俄勒冈州波特兰市）接受常规细胞学筛查的17654名女性进行随访，观察新发SIL的发生情况。在随访期间，380例新发病例患者和1037例匹配的对照受试者符合这项巢式病例对照研究的条件。使用基于PCR的方法对入组时以及之后病例诊断时（或对照受试者选择的相应时间）采集的宫颈灌洗液进行HPV DNA检测。数据以列联表形式进行分析，采用双侧P值，或在多变量分析中使用比值比（OR）及95%置信区间（CI）。
与最初HPV阴性的女性相比，入组时HPV DNA检测呈阳性的女性随后在随访期间首次被诊断为低级别SIL的可能性高3.8倍（95%CI = 2.6 - 5.5），发生高级别SIL的可能性高12.7倍（95%CI = 6.2 - 25.9）。在诊断时，HPV DNA与SIL的横断面关联极为显著（低级别SIL的OR = 44.4，95%CI = 24.2 - 81.5；高级别SIL的OR = 67.1，95%CI = 19.3 - 233.7）。HPV16是最能预测SIL的病毒类型，甚至对低级别SIL也是如此。
这些发现与HPV感染是宫颈肿瘤主要病因这一假设一致。此外，它们支持预防宫颈癌的HPV疫苗研究以及开发HPV DNA诊断检测的努力。
