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在台湾多成员家庭的高危个体中,爱泼斯坦-巴尔病毒血清学作为鼻咽癌潜在筛查标志物的研究

Epstein-Barr virus serology as a potential screening marker for nasopharyngeal carcinoma among high-risk individuals from multiplex families in Taiwan.

作者信息

Coghill Anna E, Hsu Wan-Lun, Pfeiffer Ruth M, Juwana Hedy, Yu Kelly J, Lou Pei-Jen, Wang Cheng-Ping, Chen Jen-Yang, Chen Chien-Jen, Middeldorp Jaap M, Hildesheim Allan

机构信息

Authors' Affiliations: Division of Cancer Epidemiology and Genetics;

Graduate Institute of Epidemiology, College of Public Health, National Taiwan University; Genomics Research Center, Academia Sinica;

出版信息

Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1213-9. doi: 10.1158/1055-9965.EPI-13-1262. Epub 2014 Apr 27.

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of approximately 90%. However, NPC is typically diagnosed at advanced stages, in which disease-free survival is <50%. There is, therefore, a need for clinical tools to assist in early NPC detection, particularly among high-risk individuals.

METHODS

We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N = 21) and age- and sex-matched controls (N = 84) were selected. Serum collected before NPC diagnosis was tested for ELISA-based IgA antibodies against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated.

RESULTS

EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected.

CONCLUSIONS

EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives.

IMPACT

Results from this study could inform decisions about screening biomarkers and referral thresholds for future NPC early-detection program evaluations.

摘要

背景

鼻咽癌(NPC)是一种与爱泼斯坦-巴尔病毒(EBV)相关的癌症,早期诊断时具有很高的可治愈性,5年无病生存率约为90%。然而,鼻咽癌通常在晚期才被诊断出来,此时无病生存率<50%。因此,需要临床工具来协助早期鼻咽癌检测,尤其是在高危人群中。

方法

我们评估了抗EBV IgA抗体在高危台湾人群中检测新发鼻咽癌的能力。选取了鼻咽癌病例(N = 21)以及年龄和性别匹配的对照(N = 84)。检测在鼻咽癌诊断前采集的血清中针对以下EBV肽段的基于ELISA的IgA抗体:EBNA1、VCAp18、EAp138、Ead_p47以及VCAp18 + EBNA1肽段混合物。计算敏感性、特异性和筛查项目参数。

结果

EBNA1 IgA具有最佳的性能特征。在优化的阈值下,基线时检测的EBNA1 IgA可识别出80%在随访期间发生鼻咽癌的高危个体(敏感性为80%)。然而,约40%未发生鼻咽癌的高危个体检测结果也呈阳性(假阳性)。将EBNA1 IgA作为生物标志物应用于此前未筛查的高危人群中检测新发鼻咽癌,结果显示需要筛查164人才能检测出1例鼻咽癌,且每检测出1例病例就有69人检测呈阳性。

结论

EBNA1 IgA被证明是识别新发鼻咽癌的敏感生物标志物,但未来有必要开展更多工作以开发更具特异性的筛查工具,减少假阳性数量。

影响

本研究结果可为未来鼻咽癌早期检测项目评估中筛查生物标志物和转诊阈值的决策提供参考。

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