Hildesheim A, Mann V, Brinton L A, Szklo M, Reeves W C, Rawls W E
Environmental Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Int J Cancer. 1991 Sep 30;49(3):335-40. doi: 10.1002/ijc.2910490304.
A case-control study of 766 histologically confirmed incident cases of invasive cervical cancer and 1,532 hospital and community controls was conducted in Latin America to evaluate the etiologic role of herpes simplex virus type 2 (HSV-2) and to examine whether HSV-2 interacts with other risk factors. In addition to a personal interview, all subjects were asked to donate blood samples and cervical swabs for assessment of exposure to HSV-2 and human papillomaviruses (HPVs) respectively. Ninety-eight percent of cases and 91% of controls agreed to the interview and blood collection. Women testing positive for HSV-2 antibodies were found to have a 60% increased risk of cervical cancer compared with seronegative women (95% CI = 1.3, 1.9). Control for education, sexual and reproductive behavior, prior Pap-smear screening, smoking, oral contraceptive use, HPV-6/11 DNA, or HPV-16/18 DNA detection did not materially affect this estimate. No effect modification of HSV-2 by age, HPV-6/11 DNA, pregnancies, oral contraceptive use or cigarette smoking was observed. However, a significant interaction was detected between HSV-2 and HPV-16/18. Compared with women testing negative to both virus types, those positive for HSV-2 alone had a RR of 1.2 (95% CI = 0.9, 1.6), those positive for HPV-16/18 DNA alone had a RR of 4.3 (95% CI = 3.0, 6.0), and those positive for both viruses had a RR of 8.8 (95% CI = 5.9, 13.0). These findings corroborate recent laboratory evidence of a possible biological interaction between HSV-2 and HPV-16/18 in the development of cervical cancer. Further confirmatory studies are needed, given concerns with potential misclassification of exposure by the laboratory assays utilized.
在拉丁美洲开展了一项病例对照研究，纳入766例经组织学确诊的浸润性宫颈癌新发病例以及1532例医院和社区对照，以评估2型单纯疱疹病毒（HSV-2）的病因学作用，并研究HSV-2是否与其他危险因素相互作用。除了进行个人访谈外，所有受试者均被要求捐献血液样本和宫颈拭子，分别用于评估HSV-2和人乳头瘤病毒（HPV）的暴露情况。98%的病例和91%的对照同意接受访谈和采血。与血清阴性的女性相比，HSV-2抗体检测呈阳性的女性患宫颈癌的风险增加了60%（95%可信区间=1.3，1.9）。对教育程度、性和生殖行为、既往巴氏涂片筛查、吸烟、口服避孕药使用、HPV-6/11 DNA或HPV-16/18 DNA检测进行控制，并未实质性影响这一估计值。未观察到年龄、HPV-6/11 DNA、妊娠、口服避孕药使用或吸烟对HSV-2有效应修饰作用。然而，检测到HSV-2与HPV-16/18之间存在显著的相互作用。与两种病毒检测均为阴性的女性相比，仅HSV-2呈阳性的女性相对危险度为1.2（95%可信区间=0.9，1.6），仅HPV-16/18 DNA呈阳性的女性相对危险度为4.3（95%可信区间=3.0，6.0），两种病毒均呈阳性的女性相对危险度为8.8（95%可信区间=5.9，13.0）。这些发现证实了近期实验室证据，即HSV-2与HPV-16/18在宫颈癌发生过程中可能存在生物学相互作用。鉴于对所使用的实验室检测方法可能导致暴露误分类的担忧，需要进一步的验证性研究。
