Luostarinen T, af Geijersstam V, Bjørge T, Eklund C, Hakama M, Hakulinen T, Jellum E, Koskela P, Paavonen J, Pukkala E, Schiller J T, Thoresen S, Youngman L D, Dillner J, Lehtinen M
Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki.
Int J Cancer. 1999 Mar 15;80(6):818-22. doi: 10.1002/(sici)1097-0215(19990315)80:6<818::aid-ijc4>3.0.co;2-t.
Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.
人乳头瘤病毒（HPV）16型和18型是宫颈癌的主要危险因素，而HPV 6型和11型会引发良性生殖器病变。我们想要研究致癌型和非致癌型HPV同时感染对后续宫颈癌发生风险的联合作用。对1973年至1994年间向北欧血清库捐献血样的53万名女性队列进行随访，通过与国家癌症登记处的关联来跟踪。我们确定了182例侵袭性宫颈癌的前瞻性病例，并随机选择了538例匹配对照。HPV 6、11、16、18和33血清阳性用作不同HPV感染的标志物，沙眼衣原体血清阳性和可替宁用作分别代表冒险性行为和吸烟的标志物。在HPV16血清阴性者中，HPV6/11导致宫颈鳞状细胞癌（SCC）的校正比值比（OR）为2.2，在HPV6/11血清阴性者中，HPV16导致SCC的校正比值比为5.5。假设存在相乘联合效应，HPV6/11和HPV16血清阳性的预期OR应为12，但观察到的OR为1.0。拮抗相互作用具有统计学意义（p = 0.001），并且在对可能的错误分类偏差进行确定性考量时也存在。HPV16与HPV18以及HPV16与HPV33的组合也检测到拮抗相互作用。这些结果符合HPV特异性免疫可预防SCC的概念，并支持通过接种HPV疫苗对SCC进行一级预防。
