Background: Epstein–Barr virus (EBV) is a ubiquitous gamma-herpesvirus infecting over 90% of adults worldwide. EBV is a Group 1 carcinogen, causally linked to several malignancies. Previous global estimates suggested that approximately 150,000–200,000  cancer cases in 2018 were attributable to EBV; however, these estimates only included nasopharynx carcinoma, Hodgkin lymphoma, and Burkitt lymphoma. In recent years, new evidence has emerged on EBV’s causal role in stomach cancer and lymphomas. These developments highlight the need for a re-estimate of the global- and regional- burden of cancers attributable to EBV, to better inform cancer prevention strategies.
Objectives: To estimate the global and regional burden of cancers attributable to EBV in 2022 using updated evidence on EBV-associated cancer sites and lymphoma subtypes. 
Methods: We first conducted a systematic review and meta-analysis of EBV prevalence by stomach cancer and lymphoma subtypes to calculate cancer-site–specific attributable fractions, based on studies published between 1990 and 2024 using EBER in-situ hybridisation. EBV-attributable cancer burden was then calculated by applying cancer-site–specific attributable fractions (AFs) to national cancer incidence estimates from GLOBOCAN 2022, stratified by country, sex, and age group.
Results: An estimated 250,000 new cancer cases worldwide in 2022 were attributable to EBV. The main contributors were cancers of the nasopharynx (96,000 cases; cancer-specific population attributable fraction [PAF] 80%), stomach (77,000 cases; PAF 8%), and Hodgkin lymphoma (46,000 cases; PAF 56%). The highest EBV-attributable cancers were observed in South-Eastern Asia (36,000 cases; Age Standardised Incidence Ratio [ASIR] 3.4), Eastern Asia (94,000 cases; ASIR 3.4), and Western Asia/Northern Africa (3.3). Eastern Asia accounted for 38% of the global EBV burden. Regional patterns varied markedly by cancer type, with nasopharyngeal cancer dominating in South-Eastern Asia, while gastric cancer and lymphomas were the major cancer types elsewhere.
Conclusions/Implications: EBV-attributable cancer showed a highly heterogeneous geographic and pathological distribution, ranking as the fourth leading infectious cause of cancer globally, ahead of hepatitis C virus. Given EBV’s known causal role in cancer and multiple sclerosis, these findings support investment in EBV vaccines, improved surveillance, and targeted screening strategies for high-risk populations, particularly in regions with high EBV-attributable cancer incidence, with substantial population-level health benefits.