利用 Epstein-Barr 病毒 DNA 对鼻咽拭子进行检测，作为鼻咽癌筛查项目中对血清阳性个体进行分流的一种反射性试验。

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs.

机构信息

Department of Cancer Prevention, Sun Yat-sen University Cancer Center, Guangzhou, China.

Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Clin Chem. 2022 Jul 3;68(7):953-962. doi: 10.1093/clinchem/hvac032.

DOI:10.1093/clinchem/hvac032

PMID:35325087

Abstract

BACKGROUND

Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China.

METHODS

The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals.

RESULTS

By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%).

CONCLUSIONS

Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

摘要

背景

Epstein-Barr 病毒 (EBV) DNA 在鼻咽部的检测被认为是鼻咽癌 (NPC) 的生物标志物。我们评估了其作为 NPC 筛查计划中 EBV 血清阳性者分流的反射测试的性能。

方法

研究人群嵌入在一项正在进行的 NPC 筛查试验中，包括 1111 名 EBV VCA（针对 EBV 衣壳抗原）/EBNA1（EBV 核抗原 1）-IgA 抗体（在筛查的 18237 人中）筛查阳性的参与者。采集鼻咽拭子并检测 EBVNA1 基因 EBV DNA 载量。我们评估了鼻咽拭子 EBV DNA 作为血清学高危（转介行内镜检查/MRI）和中危（转介行加速筛查）个体的反射测试的性能。

结果

截至 2019 年底，我们从 317 名血清学高危个体中检测到 20 例 NPC 病例，从 794 名中危个体中检测到 4 例 NPC 病例。当用于分流血清学高危个体时，在 20 例病例中均检测到鼻咽拭子 EBV DNA（病例阳性率：95.0%；95%CI，75.1%-99.9%），转诊率为 63.4%（201/317，95%CI，57.8%-68.7%），阳性者中的 NPC 检出率为 9.5%（19/201，95%CI，5.8%-14.4%）。结合血清学和 EBV DNA 检测对高危个体进行分流的算法的性能，其灵敏度为 72.4%（95%CI，3.0%-81.4%），特异性为 97.6%（95%CI，97.2%-97.9%）。当用于分流 EBV 血清学中危个体时，病例的阳性率为 75.0%（95%CI，19.4%-99.4%），转诊率为 61.8%（95%CI，58.4%-65.2%），阳性者中的 NPC 检出率为 0.6%（95%CI，0.1%-1.8%）。