Daling J R, Madeleine M M, McKnight B, Carter J J, Wipf G C, Ashley R, Schwartz S M, Beckmann A M, Hagensee M E, Mandelson M T, Galloway D A
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Cancer Epidemiol Biomarkers Prev. 1996 Jul;5(7):541-8.
It has now been established that infection with human papillomavirus (HPV) is necessary for the development of most cervical cancers. HPV is not sufficient for the development of cancer. Other exposures or host factors are necessary for cancer to occur. As part of an ongoing, population-based case-control study of invasive cervical cancer, we investigated the role of cigarette smoking, oral contraceptive (OC) use, and herpes simplex virus type 2 (HSV-2) as potential cofactors with HPV in the development of cervical cancer. Residents of three counties in western Washington State who were diagnosed with invasive squamous cell cervical cancer (n = 314) from January 1986 through December 1992 were interviewed about their sexual, reproductive, contraceptive, and cigarette smoking histories. Similar information was obtained from control women identified through random digit dialing (n = 672). The sera from 206 cases and 522 controls were tested for both HPV 16 capsid antibodies and HSV-2 antibodies. PCR was used to test paraffin-embedded tumor tissues for the presence of HPV DNA types 6, 16, 18, 31, 33, 35, and 39. Women with cervical cancer were more likely to be current smokers at diagnosis than population controls [relative risk (RR), 2.5; 95% confidence interval (CI), 1.8-3.4]. The risk associated with smoking was present to a similar extent among women positive and negative for HPV as measured by HPV 16 capsid antibodies and HPV DNA in the tumor tissue (cases). OC use was only important if first use was at an early age, particularly ages < or = 17 years (RR, 2.3; 95% CI, 1.4-3.8). There was only a slight risk for cervical cancer associated with antibodies to HSV-2 (RR, 1.2; 95% CI, 0.9-1.7). However, when we stratified by markers of HPV exposure, we found a significant increase in risk associated with HSV-2 among women negative for HPV 16 antibodies (RR, 2.0; 95% CI, 1.3-3.0), which was strengthened when we confined our analysis to cases whose tumors were HPV DNA negative (RR, 3.6; 95% CI, 1.6-8.0). There was no indication that cigarette smoking, OC use, or HSV-2 infection influence the ability of HPV infection to cause invasive cervical cancer. OC use may only be important in the etiology of invasive squamous cell cervical tumors if the use occurs at a critical time in the development of a woman's reproductive tract, at ages < or = 17 years. The majority of risk associated with HSV-2 was confined to HPV-negative tumors, indicating a possible separate pathway to disease that may account for 5-10% of invasive cervical cancers.
现已确定，人乳头瘤病毒（HPV）感染是大多数宫颈癌发生的必要条件。HPV感染并不足以引发癌症。癌症的发生还需要其他暴露因素或宿主因素。作为一项正在进行的、基于人群的浸润性宫颈癌病例对照研究的一部分，我们调查了吸烟、口服避孕药（OC）使用以及2型单纯疱疹病毒（HSV-2）作为HPV在宫颈癌发生中的潜在辅助因素所起的作用。对1986年1月至1992年12月期间在华盛顿州西部三个县被诊断为浸润性鳞状细胞宫颈癌的居民（n = 314）进行了访谈，询问他们的性史、生育史、避孕史和吸烟史。通过随机数字拨号确定的对照女性（n = 672）也获得了类似信息。对206例病例和522例对照的血清进行了HPV 16衣壳抗体和HSV-2抗体检测。采用聚合酶链反应（PCR）检测石蜡包埋的肿瘤组织中是否存在HPV 6、16、18、31、33、35和39型DNA。与总体对照相比，宫颈癌女性在诊断时更有可能是当前吸烟者[相对危险度（RR），2.5；95%可信区间（CI），1.8 - 3.4]。通过HPV 16衣壳抗体和肿瘤组织中的HPV DNA检测，吸烟相关风险在HPV阳性和阴性女性中程度相似（病例组）。仅在初次使用OC年龄较小，特别是年龄≤17岁时，OC使用才具有重要意义（RR，2.3；95% CI，1.4 - 3.8）。与HSV-2抗体相关的宫颈癌风险仅略有增加（RR，1.2；95% CI，0.9 - 1.7）。然而，当我们按HPV暴露标志物进行分层时，发现HPV 16抗体阴性的女性中，HSV-2相关风险显著增加（RR，2.0；95% CI，1.3 - 3.0），当我们将分析局限于肿瘤HPV DNA阴性的病例时，这种关联得到加强（RR，3.6；95% CI，1.6 - 8.0）。没有迹象表明吸烟、OC使用或HSV-2感染会影响HPV感染导致浸润性宫颈癌的能力。仅在女性生殖道发育的关键时期，即年龄≤17岁时使用OC，才可能在浸润性鳞状细胞宫颈癌的病因学中具有重要意义。与HSV-2相关的大多数风险局限于HPV阴性肿瘤，这表明可能存在一条独立的疾病途径，可能占浸润性宫颈癌的5% - 10%。
