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Systematic comparison of plasma EBV DNA, anti‐EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma
Author(s) -
Tan Lu Ping,
Tan Geok Wee,
Sivanesan Vijaya Mohan,
Goh Siang Ling,
Ng Xun Jin,
Lim Chun Shen,
Kim Wee Ric,
Mohidin Taznim Begam Binti Mohd,
Mohd Dali Nor Soleha,
Ong Siew Hoon,
Wong Chun Ying,
Sawali Halimuddin,
Yap Yoke Yeow,
Hassan Faridah,
Pua Kin Choo,
Koay Cheng Eng,
Ng Ching Ching,
Khoo Alan SooBeng
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32656
Subject(s) - nasopharyngeal carcinoma , biomarker , stage (stratigraphy) , population , epstein–barr virus , oncology , medicine , virus , carcinoma , incidence (geometry) , immunology , biology , genetics , paleontology , physics , environmental health , optics , radiation therapy
Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)‐associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost‐effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI‐W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI‐W 121 bp and ebv‐miR‐BART7‐3p were validated. Hsa‐miR‐29a‐3p and hsa‐miR‐103a‐3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI‐W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.