非高发区人群中血浆EB病毒DNA对鼻咽癌的筛查及临床应用价值

Value of plasma Epstein-Barr virus DNA detection in the screening of nasopharyngeal carcinoma and its clinical application in non-high-risk areas

目的探讨非高发区人群血浆EB病毒(EBV)DNA检测对鼻咽癌筛查的价值及临床应用。方法回顾性分析2015年11月至2020年7月就诊于四川省肿瘤医院的1153例初治鼻咽癌和244例性别年龄相匹配的健康正常人血浆EBV DNA检测结果。用实时荧光定量PCR法检测EBV DNA。分别以400拷贝/ml为临界值判断(≥400拷贝/ml判定为阳性)和优化临界值方法(将有S型扩增者均判定为阳性)统计EBV DNA阳性率。比较不同临床分期、TNM分期的患者血浆中EBV DNA拷贝数分布特征,采用受试者工作特征(ROC)曲线分析2种临界值判定方法对鼻咽癌的诊断价值。结果初治鼻咽癌组血浆EBV DNA明显高于正常对照组(P<0.001);鼻咽癌不同TNM分期患者血浆EBV DNA水平比较,差异有统计学意义(P<0.001)。2种临界值判定方法均显示,TNM及临床分期越晚,EBV DNA阳性率有升高趋势(P均<0.001)。以400拷贝/ml作为临界值,血浆EBV DNA对鼻咽癌诊断的敏感度为40.9%,特异度为100%,曲线下面积为0.704(95%CI 0.676~0.733,P<0.001)。使用优化临界值方法,敏感度增加至82.0%,特异度为99.2%,曲线下面积为0.910(95%CI 0.894~0.924,P<0.001)。结论在鼻咽癌非高发区,血浆EBV DNA以400拷贝/ml为检出下限,鼻咽癌诊断的敏感度仅为40.9%,可考虑优化核酸提取方法,从检测技术上落实临界值的优化,在保证诊断特异度的基础上提高诊断的敏感度。

Objective To investigate the value of plasma Epstein-Barr virus(EBV)DNA detection in the screening of nasopharyngeal carcinoma(NPC)and its clinical application in non-high-risk areas.Methods Plasma EBV DNA results in 1153 newly diagnosed nasopharyngeal carcinoma patients who were treated in Sichuan Cancer Hospital from 2015 to 2020 and 244 healthy control cases with matched sex and age were retrospectively analyzed.EBV DNA were detected by quantitative real-time PCR.Positive rate of EBV DNA was determined by the cutoff value of 400(≥400 copies/ml as positive)and optimization threshold method(presence of S amplification curve as positive).Further analyses were conducted to compare EBV DNA load in different clinical stage,TNM stage and regions distribution characteristics.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of the cutoff value of 400 and optimization threshold method for NPC.Results Compared with healthy controls,EBV DNA increased significantly in newly diagnosed NPC patients(P<0.001).Both evaluation methods revealed that the EBV DNA positive percentage increased with TNM and clinical stage(P<0.001).With 400 copies/ml as cutoff value,the diagnostic sensitivity and specificity were 40.85%and 100%,respectively.The area under the curve was 0.704(95%CI 0.676-0.733,P<0.001).Evaluated by the optimization threshold method,the sensitivity and specificity could improve to 82.0%and 99.2%,respectively,and the area under the curve reached 0.910(95%CI 0.894-0.924,P<0.001).Conclusions In the low prevalence area of nasopharyngeal carcinoma,the sensitivity for diagnosis of nasopharyngeal carcinoma is only 40.9%by the 400 copies/ml cutoff value method.The optimization threshold method is a better choice to improve the diagnostic sensitivity without lowering the diagnostic specificity.