Estimating the global burden of Epstein-Barr virus-related cancers

J Cancer Res Clin Oncol. 2022 Jan;148(1):31-46. doi: 10.1007/s00432-021-03824-y. Epub 2021 Oct 27.


Background: More than 90% of the adult population globally is chronically infected by the Epstein-Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers.

Method: We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein.

Conclusion: We estimated that EBV-related cases from these six cancers accounted for 239,700-357,900 new cases and 137,900-208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.

Keywords: Diffuse large B-cell lymphoma; EBV; EBV-associated cancer; EBV-related cancer; EBV-related cancer frequency; EBV-related cancer incidence; Epstein–Barr virus; Extranodal NK/T-cell lymphoma.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / therapeutic use
  • Burkitt Lymphoma / drug therapy
  • Burkitt Lymphoma / virology
  • Dacarbazine / therapeutic use
  • Doxorubicin / therapeutic use
  • Epstein-Barr Virus Infections / epidemiology*
  • Epstein-Barr Virus Infections / pathology*
  • Herpesvirus 4, Human / pathogenicity*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / virology
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / drug therapy
  • Lymphoma, Extranodal NK-T-Cell / virology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / virology
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / virology
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / virology
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology*
  • Neoplasms / virology*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / virology
  • Vinblastine / therapeutic use


  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin

Supplementary concepts

  • ABVD protocol