Utility of Serum EB Virus Zta Antibody in the Diagnostic of Nasopharyngeal Carcinoma: Evidences From 2,126 Cases and 15,644 Controls

Abstract

We collected previous published data and performed a systematical assessment for the diagnostic value of serum Zta antibody in NPC patients. Using bivariate-mixed effect model, we calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnosis odds ratio (DOR), and summary receiver operating characteristics curve (AUC) and their 95% confidence intervals (CIs). We also performed subgroup analysis to explore the heterogeneity. We included 23 studies including 24 pieces of data and 17,770 study subjects (2,126 cases and 15,644 controls). The overall combined sensitivity was 0.85 (95%CI: 0.80-0.89) and the combined specificity was 0.90 (95%CI: 0.87-0.93). The summarized AUC was 0.94 with 95%CI of 0.92-0.96. The PLR was 8.9 (95%CI: 6.4-12.2) and the NLR was 0.17(95%CI: 0.12-0.23). The diagnostic odds ratio was 53 (95%CI: 32-87). For publication year, the sensitivity was 0.88 (95%CI: 0.84-0.91) and the specificity was 0.90 (95%CI: 0.84-0.93) for ≤2006. The AUC, PLR, NLR and DOR were 0.94, 8.8, 0.13, and 64. The pooled results were similar for >2006 group. For different sample size, the pooled AUC was 0.94 for ≤Median and was 0.95 for >Median that were very close to the overall estimations. For different population setting, no overlap was found in the sensitivity (0.84 vs. 0.87), specificity (0.90 vs. 0.84), PLR (8.7 vs. 5.5), NLR (0.16 vs. 0.08-0.33), DOR (49 vs. 35), and AUC (0.94 vs. 0.92) between Asian and others. The serum EBV antibody examination has high diagnostic accuracy for early-stage NPC. The diagnostic accuracy seems not to be influenced by sample size, publication year, and ethnic. Considering the few numbers of study with non-Asian population, the present results need to be confirmed in other population setting.

Oncogenic Properties of the EBV ZEBRA Protein

“…High anti-ZEBRA IgG titers in sera correlate with poorer clinical outcome in patients [99,100]. The presence of anti-ZEBRA antibody has a high diagnostic accuracy for early-stage NPC [101]. More generally, EBV replication and expression of some early lytic cycle genes were detected in EBV-induced epithelial malignancies including NPC [102,103].…”

Serum EA-IgA and d-dimer, but not VCA-IgA, are associated with prognosis in patients with nasopharyngeal carcinoma: a meta-analysis

“…Recent studies in NPC patients have identified antibodies against EBV antigens, including early antigen (EA), viral capsid antigen (VCA) and Epstein–Barr virus nuclear antigen 1 (EBNA1) [ 25 ]. When EBV enters the lytic cycle, Rta and Zta are encoded and then EA is encoded [ 26 ]. At the end of the EBV proliferation cycle, VCA is expressed.…”

Performance of Plasma HSP90α, Serum EBV VCA IgA Antibody and Plasma EBV DNA for the Diagnosis and Prognosis Prediction of Nasopharyngeal Carcinoma

“…[16][17][18]28,29 In addition, a recent meta-analysis including 2,126 NPC patients and 15,644 controls showed that serum EBV Zta antibody exhibited a high diagnostic accuracy with a sensitivity of 0.85, a specificity of 0.9 and an AUC of 0.94 for NPC. 30 Nevertheless, serum EBV Zta antibody is not popular for the identification of NPC in clinical practices. 31 Heat shock protein (HSP), also termed stress protein, is a class of proteins that are highly expressed in cells in response to physicochemical stimuli.…”

“…Our data demonstrate that both EBV DNA and plasma HSP90α exhibit higher performance for the diagnosis of NPC than serum EBV VCA IgA antibody, which was in agreement with previous studies reporting a higher diagnostic efficacy of EBV DNA than serum EBV VCA IgA antibody for NPC. 54 In addition, serum EBV Zta antibody was also found to present a high diagnostic accuracy for NPC 30 ; however, there have been no comparisons of the performance between plasma HSP90α and serum EBV Zta antibody for the diagnosis of NPC until now. Previous studies have shown that the combination of multiple biomarkers may increase the detection of cancers.…”