Abstract：
BACKGROUND: Numerous clinical studies have validated plasma EBV DNA as a reliable biomarker for nasopharyngeal carcinoma (NPC) screening, tumor load monitoring, and prognosis prediction in endemic regions. However, the clinical relevance of plasma EBV DNA as a biomarker for NPC in non-endemic areas is still unclear.
METHODS: The pretreatment plasma EBV DNA of 1405 newly diagnosed NPC patients from three major regional hospitals in non-endemic areas were analyzed retrospectively. The medical records of 244 age- and gender-matched healthy individuals were reviewed. EBV DNA was detected using Polymerase Chain Reaction (PCR). Based on the baseline of 400 and 0 copies/mL, the distribution characteristics of the pretreatment EBV DNA load in different clinical stages and geographic regions were analyzed. The diagnostic value of pretreatment plasma EBV DNA for NPC with two baselines was evaluated using the ROC curve.
RESULTS: NPC patients had a significantly higher pretreatment EBV DNA level than healthy controls (P＜0.001). Pretreatment EBV DNA was closely associated with clinical and TNM stages in non-endemic areas, as it was in endemic areas. However, when 400 copies/mL set as the detection baseline, the sensitivity and specificity for NPC diagnosis were 40.8 % and 100 %, respectively (AUC = 0.704, cut off = 200.5 copies/mL). This sensitivity was lower than that reported in endemic regions (41.5 % - 97.1 %). Lower sensitivity may result in false negatives, missing diagnoses during NPC screening. Further investigation revealed that 39.7 % (558/1405) of NPC patients had detectable EBV DNA and S amplification curves. Optimizing the detection limit to 0 copies/mL, the sensitivity could be improved to 80.5 % (AUC = 0.901).
CONCLUSIONS: In non-endemic areas, the clinical significance of plasma EBV DNA as a biomarker for NPC was restricted due to the low detection limit of 400 copies/mL. More efficient nucleic acid extraction and detection methods are needed to optimize the detection limit and increase the clinical application of plasma EBV DNA for NPC.
METHODS: The pretreatment plasma EBV DNA of 1405 newly diagnosed NPC patients from three major regional hospitals in non-endemic areas were analyzed retrospectively. The medical records of 244 age- and gender-matched healthy individuals were reviewed. EBV DNA was detected using Polymerase Chain Reaction (PCR). Based on the baseline of 400 and 0 copies/mL, the distribution characteristics of the pretreatment EBV DNA load in different clinical stages and geographic regions were analyzed. The diagnostic value of pretreatment plasma EBV DNA for NPC with two baselines was evaluated using the ROC curve.
RESULTS: NPC patients had a significantly higher pretreatment EBV DNA level than healthy controls (P＜0.001). Pretreatment EBV DNA was closely associated with clinical and TNM stages in non-endemic areas, as it was in endemic areas. However, when 400 copies/mL set as the detection baseline, the sensitivity and specificity for NPC diagnosis were 40.8 % and 100 %, respectively (AUC = 0.704, cut off = 200.5 copies/mL). This sensitivity was lower than that reported in endemic regions (41.5 % - 97.1 %). Lower sensitivity may result in false negatives, missing diagnoses during NPC screening. Further investigation revealed that 39.7 % (558/1405) of NPC patients had detectable EBV DNA and S amplification curves. Optimizing the detection limit to 0 copies/mL, the sensitivity could be improved to 80.5 % (AUC = 0.901).
CONCLUSIONS: In non-endemic areas, the clinical significance of plasma EBV DNA as a biomarker for NPC was restricted due to the low detection limit of 400 copies/mL. More efficient nucleic acid extraction and detection methods are needed to optimize the detection limit and increase the clinical application of plasma EBV DNA for NPC.
摘要：
背景：许多临床研究已经验证了血浆EBVDNA作为鼻咽癌（NPC）筛查的可靠生物标志物，肿瘤负荷监测,流行地区的预后预测。然而,血浆EBVDNA作为非流行区NPC生物标志物的临床相关性尚不清楚.
方法：回顾性分析非地方病地区三大地区医院1405例新诊断鼻咽癌患者的血浆EBVDNA。回顾了244名年龄和性别匹配的健康个体的医疗记录。使用聚合酶链反应(PCR)检测EBVDNA。基于400和0拷贝/mL的基线，分析治疗前EBVDNA载量在不同临床分期和地理区域的分布特征。使用ROC曲线评估预处理血浆EBVDNA对具有两个基线的NPC的诊断价值。
结果：NPC患者治疗前EBVDNA水平明显高于健康对照组（P＜0.001）。治疗前EBVDNA与非流行地区的临床和TNM分期密切相关，就像在流行地区一样。然而,当400拷贝/mL设定为检测基线时，NPC诊断的敏感性和特异性分别为40.8%和100%,分别（AUC=0.704，cutoff=200.5拷贝/mL）。该敏感性低于流行地区的报告（41.5％-97.1％）。较低的灵敏度可能会导致假阴性，在NPC筛查期间漏诊。进一步调查显示，39.7％（558/1405）的NPC患者具有可检测的EBVDNA和S扩增曲线。将检测限优化为0拷贝/mL，灵敏度可提高到80.5%(AUC=0.901)。
结论：在非流行地区，血浆EBVDNA作为NPC生物标志物的临床意义由于检测限低至400拷贝/mL而受到限制.需要更有效的核酸提取和检测方法来优化检测限并增加NPC的血浆EBVDNA的临床应用。
方法：回顾性分析非地方病地区三大地区医院1405例新诊断鼻咽癌患者的血浆EBVDNA。回顾了244名年龄和性别匹配的健康个体的医疗记录。使用聚合酶链反应(PCR)检测EBVDNA。基于400和0拷贝/mL的基线，分析治疗前EBVDNA载量在不同临床分期和地理区域的分布特征。使用ROC曲线评估预处理血浆EBVDNA对具有两个基线的NPC的诊断价值。
结果：NPC患者治疗前EBVDNA水平明显高于健康对照组（P＜0.001）。治疗前EBVDNA与非流行地区的临床和TNM分期密切相关，就像在流行地区一样。然而,当400拷贝/mL设定为检测基线时，NPC诊断的敏感性和特异性分别为40.8%和100%,分别（AUC=0.704，cutoff=200.5拷贝/mL）。该敏感性低于流行地区的报告（41.5％-97.1％）。较低的灵敏度可能会导致假阴性，在NPC筛查期间漏诊。进一步调查显示，39.7％（558/1405）的NPC患者具有可检测的EBVDNA和S扩增曲线。将检测限优化为0拷贝/mL，灵敏度可提高到80.5%(AUC=0.901)。
结论：在非流行地区，血浆EBVDNA作为NPC生物标志物的临床意义由于检测限低至400拷贝/mL而受到限制.需要更有效的核酸提取和检测方法来优化检测限并增加NPC的血浆EBVDNA的临床应用。
