Anti-BNLF2b antibody for accurate diagnosis of nasopharyngeal carcinoma: a prospective comparative study

Nasopharyngeal carcinoma (NPC) is highly prevalent in Southern China and Southeast Asia and early detection significantly improves prognosis. Conventional Epstein-Barr virus (EBV) serological markers VCA-IgA and EBNA1-IgA have been widely used for NPC screening yet their performance remain unsatisfactory in real-world screening scenarios. Anti-BNLF2b antibody (P85-Ab) has emerged as a promising novel serological biomarker. However, comprehensive comparisons with conventional markers in clinically diverse cohorts incorporating diverse non-NPC patients remain insufficiently evaluated.

A prospective case-control study was performed, recruiting 122 NPC patients and 185 control subjects (99 healthy individuals and 86 patients with non-NPC disorders). Six serological EBV antibody biomarkers were evaluated: Wantai_P85-Ab, Wantai_EBNA1-IgA, Wantai_VCA-IgA, Snibe_VCA-IgA, Wantai_Zta-IgA, and Tarcine_Rta-IgG. Propensity score matching (PSM) was implemented to balance demographic covariates between NPC cases and controls. Receiver operating characteristic (ROC) curve analysis was adopted to calculate the area under curve (AUC), sensitivity and specificity for evaluating diagnostic accuracy, and concordance analysis was conducted to explore the complement value of distinct biomarkers.

After PSM, the matched analytical cohort contained 244 participants (122 NPC cases, 122 controls). Wantai_P85-Ab achieved an AUC of 0.989 (95% CI: 0.966-0.998), which was significantly higher than Wantai_EBNA1-IgA (0.942, 95% CI: 0.904-0.967), Wantai_VCA-IgA (0.874, 95% CI: 0.826-0.913), Wantai_Zta-IgA (0.847, 95% CI: 0.796-0.890), Tarcine_Rta-IgG (0.774, 95% CI: 0.716-0.824), and Snibe_VCA-IgA (0.601, 95% CI: 0.536-0.663) (all P < 0.001). Wantai_P85-Ab achieved a sensitivity of 94.26% (95% CI: 88.63-97.19) and specificity of 98.36% (95% CI: 94.22-99.55). Subgroup specificity analysis showed P85-Ab reached 100.00% (95% CI: 96.26-100.00) when distinguishing NPC from healthy controls, and 95.35% (95% CI: 88.64-98.18-) against non-NPC disease patients. Furthermore, Wantai_P85-Ab exhibited comparable sensitivity in early-stage (n = 20) NPC (95.00%, 95% CI: 76.39-99.11) and advanced-stage (n = 102) NPC (94.12%, 95% CI: 87.76-97.28). Parallel combination of Wantai_P85-Ab and Wantai_EBNA1-IgA modestly increased sensitivity to 97.54% (95% CI: 93.02-99.16) with a significant declined specificity of 92.62% (95% CI: 86.57-96.07).

This prospective comparative study with mixed clinical controls indicates that Wantai_P85-Ab has potential advantages over conventional single EBV serological markers. These findings provide supplementary clinical evidence supporting the application of P85-Ab as a primary serological biomarker for NPC screening and auxiliary diagnosis in endemic regions.