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

Cancer Res Treat. 2021 Oct;53(4):991-1003. doi: 10.4143/crt.2020.1298. Epub 2021 Jan 13.

Abstract

Purpose: This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients.

Materials and methods: Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay 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 category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by 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 (≤ 1,500 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 category (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 category or low EBV DNA level.

Keywords: Epstein–Barr virus antibodies; Nasopharyngeal carcinoma; Prognosis; TNM classification.

MeSH terms

  • Antibodies, Viral / blood*
  • Biomarkers, Tumor / blood*
  • Chemoradiotherapy / mortality*
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / virology
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • Female
  • Follow-Up Studies
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / blood
  • Nasopharyngeal Carcinoma / pathology*
  • Nasopharyngeal Carcinoma / therapy
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / blood
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Recurrence, Local / virology
  • Prognosis
  • Radiotherapy, Intensity-Modulated / mortality*
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Viral
  • Biomarkers, Tumor
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • EBV-encoded nuclear antigen 1