Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China

Abstract

In this study, we aimed to use the combined detection of multiple antibodies against Epstein-Barr virus (EBV) antigens to develop a model for screening and diagnosis of nasopharyngeal carcinoma (NPC). Samples of 300 nasopharyngeal carcinoma patients and 494 controls, including 294 healthy subjects (HC), 99 non-nasopharyngeal carcinoma cancer patients (NNPC), and 101 patients with benign nasopharyngeal lesions (BNL), were incubated with the EUROLINE Anti-EBV Profile 2, and band intensities were used to establish a risk prediction model. The nasopharyngeal carcinoma risk probability analysis based on the panel of VCAgp125 IgA, EBNA-1 IgA, EA-D IgA, EBNA-1 IgG, EAD IgG, and VCAp19 IgG displayed the best performance. When using 26.1% as the cutoff point in ROC analysis, the AUC value and sensitivity/specificity were 0.951 and 90.7%/86.2%, respectively, in nasopharyngeal carcinoma and all controls. In nasopharyngeal carcinoma and controls without the non-nasopharyngeal carcinoma and BNL groups, the AUC value and sensitivity/specificity were 0.957 and 90.7%/88.1%, respectively. The diagnostic specificity and sensitivity of the EUROLINE Anti-EBV Profile 2 assay for both nasopharyngeal carcinoma and early-stage nasopharyngeal carcinoma were higher than that of mono-antibody detection by immune-enzymatic assay and real-time PCR (EBV DNA). In the VCA-IgA-negative group, 82.6% of nasopharyngeal carcinoma patients showed high probability for nasopharyngeal carcinoma, and the negative predictive value was 97.1%. In the VCA-IgA-positive group, 73.3% of healthy subjects showed low probability. The positive predictive value reached 98.2% in this group. The nasopharyngeal carcinoma risk probability value determined by the EUROLINE Anti-EBV Profile 2 might be a suitable tool for nasopharyngeal carcinoma screening. Cancer Prev Res; 10(9); 542-50. Ó2017 AACR.

Recent advances in the management of nasopharyngeal carcinoma

“…Researchers have also explored the viral messenger RNAs and methylation status of the C-promoter region of EBV in cytology specimens as NPC biomarkers 20 . In addition, there are explorations of microRNAs in plasma as potential biomarkers 21 , 22 . Further study is required to understand the clinical values of these additional analyses.…”

Preliminary evaluation of a candidate international reference for Epstein–Barr virus capsid antigen immunoglobulin A in China

“…[1,2]Epstein-Barr virus (EBV) infection is one of the most important factors causing NPC onset. [3]EBV associated antibodies, such as virus capsid antigen (VCA-IgA) and Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), are used in the screening and diagnosis of NPC [4]and the former being one of the most widely used. [5][6][7][8]VCA-IgA antibody is usually measured by indirect immunofluorescence(IFA) [9]or enzyme-linked immunosorbent assay (ELISA) [10] with IFA considered as the "gold standard".Thanks to the presence of enzyme-labeled antibodies instead of fluorescent antibodies, the immunoenzymatic assay (IEA) doesnot need a fluorescence microscope to interpret the results,which are semi-quantitatively reported bythe titers and are widely used in southern China.…”

“…[5][6][7][8]VCA-IgA antibody is usually measured by indirect immunofluorescence(IFA) [9]or enzyme-linked immunosorbent assay (ELISA) [10] with IFA considered as the "gold standard".Thanks to the presence of enzyme-labeled antibodies instead of fluorescent antibodies, the immunoenzymatic assay (IEA) doesnot need a fluorescence microscope to interpret the results,which are semi-quantitatively reported bythe titers and are widely used in southern China. [2,3].…”

Evaluation of different immunoassays for the quantitative detection of Epstein–Barr virus capsid antigen immunoglobulin A using a candidate reference

“…[1,2]Epstein-Barr virus (EBV) infection is one of the most important factor for NPC onset. [3]EBV associated antibodies, such as virus capsid antigen (VCA-IgA) and Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA), exert an important role in the screening and diagnosis of NPC. [4]VCA-IgA is one of the most widely antibody markers used for assisting in monitoring efficacy of NPC and screening NPC.…”

“…In virtue of enzymelabeled antibodies instead of fluorescent antibodies, IEA did not need a fluorescence microscope to interpret the results which the semi-quantitative results were reported by titers was widely used in southern China. [2,3].…”