Epstein-Barr 病毒血清学抗体的波动与鼻咽癌风险：一项前瞻性筛查研究，随访 20 年。

Fluctuations of epstein-barr virus serological antibodies and risk for nasopharyngeal carcinoma: a prospective screening study with a 20-year follow-up.

机构信息

State Key Laboratory of Oncology in Southern China, Department of Epidemiology, Clinical Trial Study Center, Cancer Center, Sun Yat-sen University, Guangzhou, China.

出版信息

PLoS One. 2011 Apr 22;6(4):e19100. doi: 10.1371/journal.pone.0019100.

BACKGROUND

The impact of variation of Epstein-Barr virus (EBV) antibody titers before the development of nasopharyngeal carcinoma (NPC) is still unclear. We analyzed the fluctuations of antibodies against EBV before histopathological diagnosis to assess the risk of NPC and aimed to provide a reliable basis for screening in high risk populations.

METHODS

This study was based on a population-based screening program in Sihui County in Guangdong Province of China. A total of 18,986 subjects were recruited in 1987 and 1992, respectively. Baseline and repeated serological tests were performed for IgA antibodies against EBV capsid antigen (VCA/IgA) and early antigen (EA/IgA). Follow-up until the end of 2007 was accomplished through linkage with population and health registers. Cox proportional hazards regression model was used to estimate the relative risk of NPC in association with EBV antibodies. Time-dependent receiver operating characteristic curve (ROC) analysis was used to further evaluate the predictive ability.

RESULTS

A total of 125 NPCs occurred during an average of 16.9 years of follow-up. Using baseline information alone or together with repeated measurements, serological levels of VCA/IgA and EA/IgA were significantly associated with increased risks for NPC, with a striking dose-response relationship and most prominent during the first 5 years of follow-up. Considering the fluctuant types of serological titers observed during the first three tests, relative risk was highest among participants with ascending titers of EBV VCA/IgA antibodies with an adjusted hazard ratio (HR) of 21.3 (95% confidence interval [CI] 7.1 to 64.1), and lowest for those with decreasing titers (HR = 1.5, 95% CI 0.2 to 11.4), during the first 5 years of follow-up. Time-dependent ROC analysis showed that VCA/IgA had better predictive performance for NPC incidence than EA/IgA.

CONCLUSION

Our study documents that elevated EBV antibodies, particularly with ascending titers, are strongly associated with an increased risk for NPC.

背景

EBV 抗体滴度在鼻咽癌（NPC）发生前的变化仍不清楚。我们分析了 NPC 组织病理学诊断前 EBV 抗体的波动情况，以评估 NPC 的风险，并旨在为高危人群的筛查提供可靠的依据。

方法

本研究基于中国广东省四会县的一项人群筛查计划。分别于 1987 年和 1992 年招募了 18986 名受试者。进行了 EBV 衣壳抗原（VCA/IgA）和早期抗原（EA/IgA）的 IgA 抗体的基线和重复血清学检测。通过与人口和健康登记处的联系，完成了截至 2007 年底的随访。Cox 比例风险回归模型用于评估 NPC 与 EBV 抗体之间的相对风险。时间依赖性接收者操作特征曲线（ROC）分析用于进一步评估预测能力。

结果

在平均 16.9 年的随访中，共发生了 125 例 NPC。仅使用基线信息或与重复测量一起使用时，VCA/IgA 和 EA/IgA 的血清学水平与 NPC 的风险增加显著相关，具有明显的剂量反应关系，并且在随访的前 5 年最为明显。考虑到前三次检测中观察到的血清学滴度波动类型，在 EBV VCA/IgA 抗体滴度升高的参与者中，相对风险最高，调整后的危险比（HR）为 21.3（95%置信区间 [CI] 7.1 至 64.1），而在滴度下降的参与者中最低（HR=1.5，95%CI 0.2 至 11.4），在前 5 年的随访中。时间依赖性 ROC 分析表明，VCA/IgA 对 NPC 发生率的预测性能优于 EA/IgA。