【作者】 季明芳； 王得坤； 余元龙； 郭媛卿； 梁锦胜； 程伟民； 宗永生； 陈国雄； 吴子伯； 吴文翰； 岑信棠；

【Author】 Ji Ming-Fang Wang De-Kun Yu Yuan-Long Zong Yong-Sheng et al. Cancer Research Institute of Zhongshan City, Zhongshan City, PRC. Department of Microbiology, Departments of Surgery, and Department of Clinical Oncology, Li Ka Shing Faculty of Medine, The University of Hong Kong, Hong Kong S AR, PRC.

【机构】 中山市肿瘤研究所； 中山大学中山医学院病理系； 香港大学微生物系、肿瘤系；

【摘要】 目的:以往的研究显示个别鼻咽癌患者在确诊之前 EB病毒抗体水平升高,但很少系统性阐述鼻咽癌癌变潜伏期 EB病毒血清学的状况,本文将在此方面进行探讨。方法:在鼻咽癌高发区广东省中山市,对42,048成人进行了自1986年 12月至2002年12月共16年的EB病毒血清学和临床检查追踪研究。该研究队列人群包括42,048成人,其中男性19325 人,女性22723人,年龄在30—59岁之间(平均40．9岁)。首次筛查时间为1986年2月至1988年6月,随访至2002年 12月。在每次筛查中,全队列人群行EB病毒血清学检测、间接鼻咽镜或鼻咽纤维内窥镜检查,怀疑病例行组织活检。在首次筛查中检出EB病毒抗体阳性的人群为阳性组,EB病毒抗体阳性阴性的人群为阴性组。在首次筛查后的13年内,我们共对22,279人次进行了8次追踪检查,包括EB病毒血清学检测和间接鼻咽镜检查,其中阳性组13186人次,阴性组 9093人次。结果:在随访的16年中,我们观察到在首次进入研究队列后8个月至15年内不同时期内共有131例患者确诊为鼻咽癌。同时,动态监测了其中39例患者的EB病毒抗体水平变化,以及评估了另外68例患者在筛查期间的EB病毒抗体水平。潜伏期血清学的状态与诊断时间有关,通过血清学筛查可以提示鼻咽癌,并且的血清学阳性个体维持较高的患鼻咽癌风险。确认在鼻咽癌确诊前,机体有一个对EB病毒较强的抗体反应时期,出现了以EB病毒抗体水平的持续升高为标志的血清学窗口期,该时间可能早干诊断10年前,但平均为37+／-28月。本研究队列中约90％的病例或在首次筛查前或在之后进入血清学窗口期。筛查后早期阶段诊断的病例,在首次筛查时已进入血清学窗口期,这些病例处于鼻咽癌癌变过程中潜伏期的更早期,比那些在筛查后进入血清学窗口期的病例(平均90个月)得到更早的确诊(平均27个月)。随着时间的延续,阳性人群患癌的风险随筛查前已进入血清学窗口期的阳性病例的不断被检出而下降。结论:这一结果显示:EB病毒抗体水平的持续升高是发生在鼻咽癌癌变潜伏期的普遍事件,并且提示重复血清学筛查是监测肿瘤出现临床表现之前的重要指标。更多还原

【Abstract】 Objective: Previous studies have shown that EBV antibody levels of individual NPC patients are elevated before the cancer is diagnosed, but few systematically document the serologic status of the patients during the preclinical phase in the development of the cancer. Methods: In a follow-up study extending 16 years, we have clinically monitored 131 NPC cases for different periods of 8 months to 15 years between enrollment and the time when the cancer was diagnosed. We also concurrently monitored EBV antibody levels of 39 of these cases and assessed the serologic status of another 68 cases during these interim periods. The preclinical serologic profiles were related to times of diagnosis, prediction of NPC by serologic screening and risk of the cancer sustained by the seropositive subjects, respectively. Results: The results identified a period of vigorous antibody response to EBV immediately preceding diagnosis of the cancer by up to 10 years. Marked by a sustained elevation of VCA IgA antibody level, the mean duration of this window period was 37 +/-28 months. 90% of the study cases either had entered the serologic window before or would do so after enrollment The former cases are at more advanced stage of tumor progression in the predinical phase of NPC development, and are diagnosed earlier [median = 27 months], than those who entered the window after enrollment [median = 90 months]. Prediction of NPC by serologic screening and risk of the cancer sustained by seropositive subjects declined with time in proportion to the number of those cases remaining, which had entered the serologic window before screening. Conclusion: The results show that sustained elevation of antibody level is a common event taking place during the predinical phase of NPC development and suggest that repeated serologic screening could serve as a sentinel to monitor tumor progression before it becomes clinically manifested更多还原