Prognostic Value of Serum Epstein-Barr Virus Antibodies and Their Correlation with TNM Classification in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Purpose This study assessed the correlation between EBV biomarkers and the 8th American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), and IgA antibodies against Epstein-Barr nuclear antigen1 (EBNA1-IgA) and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced NPC patients. Materials and Methods Serum EBV antibody levels were measured by ELISA in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). Results Rta-IgG and Zta-IgA levels were positively correlated with the N stage and clinical stage. Patients with high Rta-IgG levels (>29.07 U/mL) showed a significantly inferior prognosis as indicated by progression-free survival (PFS) (77% vs. 89.8%, p=0.004), distant metastasis-free survival (DMFS) (88.3% vs. 95.8%, P=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤1500 copies/ml), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p<0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T stage (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS and LRFS (both p<0.05). Conclusion Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T stage or low EBV DNA level.