Epstein-Barr virus and risk of non-Hodgkin lymphoma in the cancer prevention study-II and a meta-analysis of serologic studies

Int J Cancer. 2015 Jan 1;136(1):108-16. doi: 10.1002/ijc.28971. Epub 2014 Jun 5.


Epstein-Barr virus (EBV) causes rare, malignant lymphomas. The role of EBV in other non-Hodgkin lymphomas (NHLs) remains unclear, but mildly reduced immune function could lead to reactivation of EBV and subsequent NHL. We examined the association between prospectively-collected plasma EBV antibodies and NHL risk in the Cancer Prevention Study-II (CPS-II) Nutrition Cohort and conducted a meta-analysis of our and published results. The CPS-II study included 225 NHL cases and 2:1 matched controls. No associations were observed between EBV serostatus or antibody levels and risk of NHL overall. However, when including only the three most common types of NHL (diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), high compared to low early antigen (EA-D) diffuse and BZLF1-encoded replication activator antibodies were associated with approximately 60% higher risk of NHL. Odds ratios (ORs) for EBV nuclear antigen-1 and viral capsid antigen (VCA)-p18 were elevated but not statistically significant. In the meta-analysis, both EA (summary OR = 1.52, 95% confidence interval (CI): 1.16-2.00) and VCA (summary OR = 1.20, 95% CI: 1.00-1.44) were positively associated with NHL risk. These results suggest EBV may be associated with a wider spectrum of NHL subtypes, but further study is needed to confirm and fully understand these associations.

Keywords: Epstein-Barr virus; multiplex serology; non-Hodgkin lymphoma; prospective study.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Antigens, Viral / immunology
  • Case-Control Studies
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / prevention & control
  • Epstein-Barr Virus Infections / virology*
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Lymphoma, Non-Hodgkin / blood
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / prevention & control
  • Lymphoma, Non-Hodgkin / virology*
  • Risk


  • Antibodies, Viral
  • Antigens, Viral