ObjectiveEpstein–Barr virus-related antibody seromarkers including VCA-IgA, EA-IgA, EBNA1-IgA, and Rta-IgG are used as markers for the detection of nasopharyngeal carcinoma (NPC). This meta-analysis was conducted to evaluate the diagnostic performance of their use in combined assays. MethodsComputerized searching of five electronic databases, supplemented by manual searching methods, was performed to identify pertinent articles. Diagnostic accuracy parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC), were calculated with corresponding 95% confidence intervals (CIs). ResultsTwenty-one studies with 4753 NPC cases and 31875 non-NPC controls were included. The pooled sensitivities for VCA-IgA+EA-IgA, VCA-IgA+EBNA1-IgA, VCA-IgA+Rta-IgG, and VCA-IgA+ EA-IgA+Rta-IgG were 0.89, 0.93, 0.94, and 0.94, respectively. Pooled specificities were 0.89, 0.88, 0.90, and 0.95, respectively. The PLRs were 8.1, 7.6, 9.4, and 17.4, respectively. Pooled NLRs were 0.12, 0.08, 0.07, and 0.07, respectively. Pooled DORs were 66, 95, 135, and 261, respectively. Pooled AUCs were 0.94, 0.96, 0.97, and 0.94, respectively. ConclusionThese four combined assays based on EBV-related antibodies show diagnostic accuracy. The three-marker assay of VCA-IgA, EA IgA, and Rta-IgG has the best performance. Given the aspect of cost-benefit, VCA-IgA combined with EBNA1-IgA or Rta-IgG could become the preferred serodiagnostic strategy for NPC screening and early diagnosis.