以EBV DNA 或抗体对无症状EB病毒感染者进行人群筛查，提高了鼻咽癌的诊断和患者的生存率。然而，当前筛查策略的阳性预测值即使在鼻咽癌地区流行的地方也不尽人意。我们设计了一个代表EBV编码序列高排序B细胞表位的肽库，以挖掘鼻咽癌的新的血清学生物标志物。在一项回顾性病例对照研究后，通过大规模前瞻性筛查计划验证了新的生物标志物抗BNLF2b总抗体(P85-Ab)的性能，并与标准的两抗体筛查方法(EBV核抗原1[EBNA1]-IgA和EBV特异性病毒衣壳抗原[VCA]-IgA)进行比较。在回顾性病例对照研究中，P85-Ab是鼻咽癌筛查最有前景的生物标志物，具有较高的敏感性(94.4%; 95% CI, 86.4 to 97.8)和特异性(99.6%; 95% CI, 97.8 to 99.9)。在前瞻性队列中的24,852名符合条件的参与者中，确定了47例鼻咽癌病例(早期38例)。P85-Ab显示出比两抗体方法更高的敏感性(97.9% vs. 72.3%; ratio, 1.4 [95% CI, 1.1 to 1.6])，更高的特异性(98.3% vs. 97.0%; ratio, 1.01 [95% CI, 1.01 to 1.02])和更高的阳性预测值(10.0% vs. 4.3%; ratio, 2.3 [95% CI, 1.8 to 2.8])。P85-Ab与两抗体方法的联合显著提高了阳性预测值，达到44.6% (95% CI, 33.8 to 55.9)，敏感性为70.2% (95% CI, 56.0 to 81.4)。我们的结果表明，P85-Ab是鼻咽癌筛查的一种有前景的新生物标志物，具有比标准的两抗体方法更高的敏感性、特异性和阳性预测值。(中国国家重点研发计划等资助；ClinicalTrials.gov编号NCT04085900)。Copyright © 2023 Massachusetts Medical Society.

Population screening of asymptomatic persons with Epstein-Barr virus (EBV) DNA or antibodies has improved the diagnosis of nasopharyngeal carcinoma and survival among affected persons. However, the positive predictive value of current screening strategies is unsatisfactory even in areas where nasopharyngeal carcinoma is endemic.We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biomarkers for nasopharyngeal carcinoma. After a retrospective case-control study, the performance of the novel biomarker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody-based screening method (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA).P85-Ab was the most promising biomarker for nasopharyngeal carcinoma screening, with high sensitivity (94.4%; 95% confidence interval [CI], 86.4 to 97.8) and specificity (99.6%; 95% CI, 97.8 to 99.9) in the retrospective case-control study. Among the 24,852 eligible participants in the prospective cohort, 47 cases of nasopharyngeal carcinoma (38 at an early stage) were identified. P85-Ab showed higher sensitivity than the two-antibody method (97.9% vs. 72.3%; ratio, 1.4 [95% CI, 1.1 to 1.6]), higher specificity (98.3% vs. 97.0%; ratio, 1.01 [95% CI, 1.01 to 1.02]), and a higher positive predictive value (10.0% vs. 4.3%; ratio, 2.3 [95% CI, 1.8 to 2.8]). The combination of P85-Ab and the two-antibody method markedly increased the positive predictive value to 44.6% (95% CI, 33.8 to 55.9), with sensitivity of 70.2% (95% CI, 56.0 to 81.4).Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT04085900.).Copyright © 2023 Massachusetts Medical Society.