Cancer Council NSW, Cancer Epidemiology Research Unit, Sydney, NSW, Australia.
J Natl Cancer Inst. 2012 Jan 18;104(2):147-58. doi: 10.1093/jnci/djr499. Epub 2012 Jan 6.
The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing background risks of esophageal cancer.
We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided.
We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036).
We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers.
人乳头瘤病毒（HPV）在食管鳞状细胞癌发病机制中的作用尚不清楚。我们在六个具有不同食管癌背景风险的地区进行的现有病例对照研究中，检测了食管鳞状细胞癌与血清中 28 种集中测量的 HPV 血清学标志物之间的关联。
我们使用集中的多重血清学方法检测了来自六个病例对照研究的 1561 例病例和 2502 例对照的血清样本，以检测针对主要 HPV 衣壳蛋白（L1）和/或八种高危型、两种低危型和四种皮肤型 HPV 的早期蛋白 E6 和/或 E7 的抗体。使用条件逻辑回归估计了研究特异性比值比（OR）及其相应的 95%置信区间（CI），并进行了吸烟、饮酒和其他潜在混杂因素的调整。使用线性混合效应方法或联合固定效应方法计算了汇总比值比和 95%置信区间。所有统计检验均为双侧。
我们发现食管鳞状细胞癌与 HPV16 的 E6 抗体（OR = 1.89，95%CI = 1.09 至 3.29，P =.023）和 HPV6（OR = 2.53，95%CI = 1.51 至 4.25，P <.001）之间存在统计学显著关联，但与其他测试的 HPV 类型无关。对于任何测试的 HPV 类型，食管鳞状细胞癌与 E7 抗体之间均无统计学显著关联。同时检测到 HPV16 E6 和 E7 的血清阳性率很低（4 例病例，2 例对照；OR = 5.57，95%CI = 0.90 至 34.35；P =.064）。我们还发现食管鳞状细胞癌与高危黏膜型 HPV33 L1 的衣壳抗体之间存在统计学显著关联（OR = 1.30，95%CI = 1.00 至 1.69，P =.047）和低危黏膜型 HPV6（OR = 1.22，95%CI = 1.05 至 1.42，P =.010）和 HPV11（OR = 1.30，95%CI = 1.09 至 1.56，P =.0036）。
我们在研究人群中发现了食管鳞状细胞癌与 HPV 之间有限的血清学关联证据。尽管 HPV 似乎不是食管鳞状细胞癌的重要危险因素，但我们不能排除某些 HPV 类型可能与一小部分癌症有关。
