Hakama M, Luostarinen T, Hallmans G, Jellum E, Koskela P, Lehtinen M, Thoresen S, Youngman L, Hakulinen T
Finnish Cancer Registry, Helsinki.
Cancer Causes Control. 2000 Oct;11(9):783-90. doi: 10.1023/a:1008976703797.
To estimate the joint effects of infections with human papillomavirus type 16 (HPV16) and Chlamydia trachomatis and smoking on the risk of cervical cancer. To study whether the joint effects can be accounted for by misclassification in the HPV serology.
A nested case-control study with incidence density sampling was conducted in three cohorts of 530,000 women, who donated serum samples to three Nordic serum banks in 1973-1994. The main outcome measure is the odds ratio (OR) of incidence rates of invasive cervical squamous cell carcinoma (SCC) among those seropositive for HPV16 and/or C. trachomatis and/or with increased levels of cotinine in serum compared to those negative for all the three exposures.
Two hundred eight women with SCC and 624 matched controls were identified during a mean follow-up of 5 years through linkage to the national cancer registries. Exposure to past infections and smoking was defined by presence of specific IgG antibodies to HPV16 and C. trachomatis and increased levels of serum cotinine. Observed ORs were compared to OR = 20 for HPV16 and accounting the differences for by misclassification bias. OR = 20 was elected as a gold standard on the basis of other studies with PCR-based analyses and a follow-up design. Each of the three exposures was associated with an increased risk of SCC (OR = 5.4 for HPV16, 3.4 for C. trachomatis and 1.8 for cotinine). The interaction was antagonistic (observed OR = 2.5 among those positive for all three exposures as compared to OR = 33 expected on the basis of multiplicative single effects (p = 0.047)). The antagonism could not totally be accounted for by any credible combination of sensitivity and specificity of HPV16 serology.
HPV16, C. trachomatis, and smoking are likely to be risk factors of SCC with strong antagonistic joint effect. Non-differential misclassification in serology for HPV16 could be ruled out (but only some types of differential) as an alternative explanation for the observed antagonism.
评估16型人乳头瘤病毒（HPV16）感染、沙眼衣原体感染及吸烟对宫颈癌风险的联合影响。研究联合影响是否可由HPV血清学分类错误来解释。
在三个队列共530,000名女性中开展一项采用发病密度抽样的巢式病例对照研究，这些女性在1973年至1994年间向三个北欧血清库捐赠了血清样本。主要结局指标是HPV16和/或沙眼衣原体血清学阳性和/或血清中可替宁水平升高者与三种暴露均为阴性者相比，浸润性宫颈鳞状细胞癌（SCC）发病率的比值比（OR）。
通过与国家癌症登记处的关联，在平均5年的随访期间确定了208例SCC女性患者和624例匹配对照。既往感染和吸烟暴露通过HPV16和沙眼衣原体特异性IgG抗体的存在以及血清可替宁水平升高来定义。将观察到的OR与HPV16的OR = 20进行比较，并考虑分类错误偏倚的差异。基于其他基于PCR分析和随访设计的研究，将OR = 20选为金标准。三种暴露中的每一种都与SCC风险增加相关（HPV16的OR = 5.4，沙眼衣原体的OR = 3.4，可替宁的OR = 1.8）。相互作用是拮抗的（与基于单一效应相乘预期的OR = 33相比，三种暴露均为阳性者中观察到的OR = 2.5，p = 0.047）。HPV16血清学敏感性和特异性的任何可信组合都不能完全解释这种拮抗作用。
HPV16、沙眼衣原体和吸烟可能是SCC的危险因素，具有强烈的拮抗联合效应。可以排除HPV16血清学中的非差异性分类错误（但仅某些类型的差异性分类错误）作为观察到的拮抗作用的另一种解释。
