血浆 Epstein-Barr 病毒 DNA 分析用于筛查鼻咽癌。

Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

机构信息

From the Li Ka Shing Institute of Health Sciences (K.C.A.C., W.K.J.L., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., R.W.K.C., Y.M.D.L.), the Department of Chemical Pathology (K.C.A.C., W.K.J.L., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., R.W.K.C., Y.M.D.L.), State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer (K.C.A.C., W.K.J.L., S.L.C., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., E.P.H., B.B.Y.M., R.W.K.C., S.-F.L., A.T.C.C., Y.M.D.L.), Department of Otorhinolaryngology, Head and Neck Surgery (J.K.S.W., W.K.J.L., A.C.H.), Department of Imaging and Interventional Radiology (A.K.), Jockey Club School of Public Health and Primary Care (B.C.Y.Z.), and Department of Clinical Oncology (S.L.C., E.P.H., B.B.Y.M., S.-F.L., A.T.C.C.), Chinese University of Hong Kong, Prince of Wales Hospital - all in Hong Kong.

出版信息

N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717.

DOI:10.1056/NEJMoa1701717

PMID:28792880

Abstract

BACKGROUND

Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons.

METHODS

We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI).

RESULTS

A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.

CONCLUSIONS

Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399 .).

摘要

背景

循环游离 EBV 病毒（EBV）DNA 是鼻咽癌的生物标志物。我们进行了一项前瞻性研究，以探究血浆样本中的 EBV DNA 是否可用于无症状人群的鼻咽癌早期筛查。

方法

我们分析了无症状人群的血浆样本中的 EBV DNA。最初结果阳性的参与者在大约 4 周后进行重复检测，而血浆中 EBV DNA 持续阳性的参与者则接受鼻内镜检查和磁共振成像（MRI）。

结果

共有 20174 名参与者接受了筛查。1112 名参与者（5.5%）的血浆样本中可检测到 EBV DNA，其中 309 名（所有参与者的 1.5%，最初阳性检测者的 27.8%）的重复样本 EBV DNA 持续阳性。在这 309 名参与者中，300 名接受了内镜检查，275 名接受了内镜检查和 MRI；其中 34 名患有鼻咽癌。通过筛查确定的鼻咽癌患者中，Ⅰ期或Ⅱ期疾病的比例显著高于历史队列（卡方检验，71%比 20%；P<0.001），且无进展生存 3 年率更高（97%比 70%；风险比，0.10；95%置信区间，0.05 至 0.18）。9 名参与者拒绝进一步检测，其中 1 名在入组后 32 个月时出现晚期鼻咽癌。在检测后 1 年内，血浆 EBV DNA 阴性的鼻咽癌患者仅 1 例。血浆 EBV DNA 筛查鼻咽癌的敏感性和特异性分别为 97.1%和 98.6%。