Prognostic value of anti-Epstein-Barr virus antibodies in nasopharyngeal carcinoma (NPC)

Abstract

Introduction: Epstein-Barr virus (EBV) is a ubiquitous human herpes virus with worldwide infection. It is associated with Burkitt's lymphoma in Africa and nasopharyngeal cancer (NPC) in Asian countries. EBV-coded DNA was found to be present in epithelial elements of NPC, and is usually associated with non-keratinizing (WHO type II) or undifferentiated carcinoma (WHO type III). Transcriptional analyses of EBV genome expression in NPC demonstrate an activated viral state in some of these tumors, leading to elevated levels of serum anti-viral capsid antigen (VCA) antibody in NPC patients.

Methods: Eighty patients with histological diagnoses of NPC according to the 1978 WHO classification were referred to the Department of Radiation Oncology at Chang-Hua Christian Hospital for curative radiotherapy from 1985 to 1995. The patients were staged according to the AJCC staging system. A mean dose of 7,020 cGy in 39 fractions was delivered to the primary tumor using a telecobalt-60 unit or 6-10 MV X-ray linear accelerator. Pre- and postradiotherapy serum levels of anti-EBV/VCA IgG and IgA were determined for all patients using the indirect immunoperoxidase assay (IPA). Multivariate analysis was done to determine which factors affected the patients' treatment outcome and survival.

Results: Five patients were excluded from this study due to incomplete radiotherapy, leaving 75 patients eligible for analysis. Overall local control was 77.3%, with a mean disease-free interval of 19.7 months. Factors affecting local control included radiation dose and pretreatment anti-EBV/VCA IgG titer. The overall 5-year actuarial survival for the 75 patients was 75%, with a median survival of 129.5 months. The 5-year actuarial survival rates for stage I + II, III, and IV patients were 90%, 40%, and 45%, respectively. Prognostic factors for survival included tumor histological type and pretreatment anti-EBV/VCA IgA titer, while prognostic factors for local control included total radiation dose received and pretreatment anti-EBV/VCA IgG titer.

Conclusion: We found that there was a significant difference in the geometric mean titer of anti-EBV/VCA IgA antibodies before and after radiotherapy. Prognostic factors affecting NPC patients' actuarial survival included tumor histology and pretreatment IgA titer, while prognostic factors for local control of NPC included total radiation dose received and pretreatment IgG titer.