---
title: "Global Attributable Fraction of Epstein-Barr Virus Across Lymphoma Subtypes: Systematic Review and"
id: "pubmed-41947331"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-41947331"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/41947331/"
doi: "10.1002/ijc.70468"
published_at: "2026-08-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Global Attributable Fraction of Epstein-Barr Virus Across Lymphoma Subtypes: Systematic Review and
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-41947331
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/41947331/)
- **DOI:** [10.1002/ijc.70468](https://doi.org/10.1002%2Fijc.70468)
- **Published At:** 2026-08-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This systematic review and meta-analysis synthesized data from 307 eligible studies, covering more than **21,140** lymphoma cases diagnosed between 1990 and 2024. - EBV presence was assessed using **EBV-encoded RNA (EBER) in situ hybridisation**, and pooled prevalences with 95% confidence intervals were calculated by lymphoma subtype, HIV status, and geographical region. - In HIV-negative patients, pooled EBV prevalence estimates were: Diffuse large B-cell lymphoma (DLBCL) 10.8% (95% CI 8.6%–13.5%), Burkitt lymphoma (BL) 45.8% (35.2%–56.8%), Hodgkin lymphoma 53.0% (46.9%–58.9%), plasmablastic lymphoma (PBL) 52.5% (29.6%–74.4%), extranodal NK/T-cell lymphoma (ENKTL) 92.4% (83.3%–96.7%), and follicular lymphoma 5.1% (2.7%–9.4%). - EBV prevalence was substantially higher in tumors from persons living with HIV (PLHIV) compared with HIV-negative tumors for several subtypes: DLBCL 43.6% (31.5%–56.5%), BL 43.3% (27.9%–60.2%), and PBL 79.4% (65.6%–88.6%). - Geographic heterogeneity was limited overall; the principal regional difference observed was in BL, with near-universal EBV positivity reported in East African Burkitt lymphoma. - The analysis provides comprehensive evidence of EBV's substantial contribution to multiple lymphoma subtypes and highlights increased importance in lymphomas arising in PLHIV. - The authors emphasize that these data can inform estimates of the global burden of EBV-related disease and support public health and clinical strategies such as **vaccination**, earlier diagnosis, or **targeted therapies**. - Study scope, inclusion period (1990–2024), EBV detection method (EBER ISH), pooled prevalence estimates, and the number of included studies and cases are explicitly reported in the source. - Details beyond the abstract (for example, study-by-study quality assessment, statistical methods, inclusion/exclusion criteria, or full regional breakdowns) were not reported in the source abstract provided here.
## Clinical Analysis & Structured Key Points
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Epub 2026 Apr 7. # Attributable Fraction of Epstein-Barr Virus in Subtypes of Lymphoma: A Systematic Review and Global Meta-Analysis [Mayo Hirabayashi](https://pubmed.ncbi.nlm.nih.gov/?term=Hirabayashi+M&cauthor_id=41947331)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#full-view-affiliation-1 "Division of Prevention, Institute for Cancer Control, National Cancer Center, Tokyo, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#full-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Damien Georges](https://pubmed.ncbi.nlm.nih.gov/?term=Georges+D&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#full-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Jean-Damien Combes](https://pubmed.ncbi.nlm.nih.gov/?term=Combes+JD&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#full-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Gary M Clifford](https://pubmed.ncbi.nlm.nih.gov/?term=Clifford+GM&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#full-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France.") Affiliations Expand ### Affiliations * 1 Division of Prevention, Institute for Cancer Control, National Cancer Center, Tokyo, Japan. * 2 International Agency for Research on Cancer (IARC/WHO), Early Detection, Prevention and Infections Branch, Lyon, France. * PMID: **41947331** * DOI: [ 10.1002/ijc.70468 ](https://doi.org/10.1002/ijc.70468) Item in Clipboard Meta-Analysis # Attributable Fraction of Epstein-Barr Virus in Subtypes of Lymphoma: A Systematic Review and Global Meta-Analysis Mayo Hirabayashi et al. Int J Cancer. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Cancer Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Cancer%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Cancer%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) . 2026 Aug 15;159(4):896-903. doi: 10.1002/ijc.70468. Epub 2026 Apr 7. ### Authors [Mayo Hirabayashi](https://pubmed.ncbi.nlm.nih.gov/?term=Hirabayashi+M&cauthor_id=41947331)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#short-view-affiliation-1 "Division of Prevention, Institute for Cancer Control, National Cancer Center, Tokyo, Japan.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#short-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Damien Georges](https://pubmed.ncbi.nlm.nih.gov/?term=Georges+D&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#short-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Jean-Damien Combes](https://pubmed.ncbi.nlm.nih.gov/?term=Combes+JD&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#short-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France."), [Gary M Clifford](https://pubmed.ncbi.nlm.nih.gov/?term=Clifford+GM&cauthor_id=41947331)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41947331/#short-view-affiliation-2 "International Agency for Research on Cancer \(IARC/WHO\), Early Detection, Prevention and Infections Branch, Lyon, France.") ### Affiliations * 1 Division of Prevention, Institute for Cancer Control, National Cancer Center, Tokyo, Japan. * 2 International Agency for Research on Cancer (IARC/WHO), Early Detection, Prevention and Infections Branch, Lyon, France. * PMID: **41947331** * DOI: [ 10.1002/ijc.70468 ](https://doi.org/10.1002/ijc.70468) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract There is evidence for a causal role of Epstein-Barr virus (EBV), a known carcinogen, in an increasing number of lymphoma subtypes, but a systematic evaluation of EBV attributable fraction is lacking. We conducted a systematic review and meta-analysis of EBV prevalence in lymphoma subtypes from 1990 to 2024, stratified by HIV status and geographical region. For each subtype, we calculated pooled prevalence and corresponding 95% confidence intervals (CIs) of EBV, measured by EBV-encoded RNA in situ hybridisation. 307 eligible studies, including > 21,140 lymphoma cases, were included. In HIV-negative persons, EBV pooled prevalence was 10.8% (95% CI 8.6%-13.5%) in Diffuse large B-cell lymphoma (DLBCL), 45.8% (35.2%-56.8%) in Burkitt lymphoma (BL), 53.0% (46.9%-58.9%) in Hodgkin lymphoma, 52.5% (29.6%-74.4%) in plasmablastic lymphoma, 92.4% (83.3%-96.7%) in extranodal NK/T-cell lymphoma (ENKTL), and 5.1% (2.7%-9.4%) in follicular lymphoma. EBV prevalence was higher among tumors diagnosed among persons living with HIV (PLHIV), for DLBCL (43.6% (95% CI 31.5%-56.5%)), BL (43.3% (27.9%-60.2%)), and PBL (79.4% (65.6%-88.6%)), compared to HIV-negative tumors. BL was the only subtype with evidence of heterogeneity in EBV positivity by region, with near-universal EBV positivity in East African BL. This provides the first systematic and comprehensive evidence on EBV's substantial contribution to lymphoma, highlighting its particular importance in lymphomas arising in PLHIV. These data can contribute to estimating the complete burden of EBV-related disease and inform public health and clinical strategies, including vaccines, early diagnosis, or targeted therapies. **Keywords:** Epstein–Barr virus; attributable fraction; lymphoma. © 2026 WHO International Agency for Research on Cancer. WHO International Agency for Research on Cancer retains copyright and all other rights in the manuscript of this article as submitted for publication. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Estimating the global burden of Epstein-Barr virus-related cancers. ](https://pubmed.ncbi.nlm.nih.gov/34705104/) Wong Y, Meehan MT, Burrows SR, Doolan DL, Miles JJ.Wong Y, et al.J Cancer Res Clin Oncol. 2022 Jan;148(1):31-46. doi: 10.1007/s00432-021-03824-y. Epub 2021 Oct 27.J Cancer Res Clin Oncol. 2022.PMID: 34705104Free PMC article.Review. * [ Diffuse large B-cell lymphoma in a South African cohort with a high HIV prevalence: an analysis by cell-of-origin, Epstein-Barr virus infection and survival. ](https://pubmed.ncbi.nlm.nih.gov/32305135/) Cassim S, Antel K, Chetty DR, Oosthuizen J, Opie J, Mohamed Z, Verburgh E.Cassim S, et al.Pathology. 2020 Jun;52(4):453-459. doi: 10.1016/j.pathol.2020.02.007. Epub 2020 Apr 15.Pathology. 2020.PMID: 32305135Free PMC article. * [ Clinical characteristics and outcomes in Epstein-Barr virus-positive diffuse large B-cell lymphoma: a multicenter retrospective study. ](https://pubmed.ncbi.nlm.nih.gov/41234454/) Kiliç Güneş E, Afacan Öztürk HB, Kiriktir E, Dikyar A, Uğur B, Güneş AK, Ayli M.Kiliç Güneş E, et al.Turk J Med Sci. 2025 Sep 2;55(5):1113-1121. doi: 10.55730/1300-0144.6066. eCollection 2025.Turk J Med Sci. 2025.PMID: 41234454Free PMC article. * [ Frequent traces of EBV infection in Hodgkin and non-Hodgkin lymphomas classified as EBV-negative by routine methods: expanding the landscape of EBV-related lymphomas. ](https://pubmed.ncbi.nlm.nih.gov/32483241/) Mundo L, Del Porro L, Granai M, Siciliano MC, Mancini V, Santi R, Marcar L, Vrzalikova K, Vergoni F, Di Stefano G, Schiavoni G, Segreto G, Onyango N, Nyagol JA, Amato T, Bellan C, Anagnostopoulos I, Falini B, Leoncini L, Tiacci E, Lazzi S.Mundo L, et al.Mod Pathol. 2020 Dec;33(12):2407-2421. doi: 10.1038/s41379-020-0575-3. Epub 2020 Jun 1.Mod Pathol. 2020.PMID: 32483241Free PMC article. * [ Seroepidemiological analysis and literature review of the prevalence of Epstein-Barr virus and herpesvirus infections in pediatric cases with non-Hodgkin lymphoma in Central Europe. ](https://pubmed.ncbi.nlm.nih.gov/30977593/) Vaillant V, Reiter A, Zimmermann M, Wagner HJ.Vaillant V, et al.Pediatr Blood Cancer. 2019 Jul;66(7):e27752. doi: 10.1002/pbc.27752. Epub 2019 Apr 12.Pediatr Blood Cancer. 2019.PMID: 30977593Review. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=41947331) ## References 1. 1. M. A. Epstein , B. G. Achong , and Y. M. Barr , “Virus Particles in Cultured Lymphoblasts From Burkitt's Lymphoma,” Lancet 283, no. 7335 (1964): 702–703. 2. 1. A. S. Tatyana , B. D. Stollar , J. L. Sullivan , K. Luzuriaga , and D. A. Thorley‐Lawson , “Peripheral B Cells Latently Infected With Epstein–Barr Virus Display Molecular Hallmarks of Classical Antigen‐Selected Memory B Cells,” Proceedings of the National Academy of Sciences of the United States of America 102, no. 50 (2005): 18093–18098. 3. 1. L. S. Young and A. B. Rickinson , “Epstein–Barr Virus: 40 Years on,” Nature Reviews Cancer 4, no. 10 (2004): 757–768. 4. 1. K. Bjornevik , M. Cortese , B. C. Healy , et al., “Longitudinal Analysis Reveals High Prevalence of Epstein–Barr Virus Associated With Multiple Sclerosis,” Science 375, no. 6578 (2022): 296–301. 5. 1. International Agency for Research on Cancer, “A Review of Human Carcinogens. 100 B,” in IARC Monographs on the Evaluation of Carcinog Enic Risks to Humans (International Agency for Research on Cancer, 2012). Show all 25 references ## Publication types * Systematic Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Systematic+Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Systematic+Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Meta-Analysis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Meta-Analysis%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Meta-Analysis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) ## MeSH terms * Burkitt Lymphoma / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Burkitt+Lymphoma%2Fepidemiology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Burkitt+Lymphoma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Burkitt Lymphoma / virology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Burkitt+Lymphoma%2Fvirology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Burkitt+Lymphoma) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Epstein-Barr Virus Infections* / complications Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Epstein-Barr+Virus+Infections%2Fcomplications%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Epstein-Barr+Virus+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Epstein-Barr Virus Infections* / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Epstein-Barr+Virus+Infections%2Fepidemiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Epstein-Barr+Virus+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Epstein-Barr Virus Infections* / virology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Epstein-Barr+Virus+Infections%2Fvirology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Epstein-Barr+Virus+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * HIV Infections / epidemiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV+Infections%2Fepidemiology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * HIV Infections / virology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22HIV+Infections%2Fvirology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=HIV+Infections) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Herpesvirus 4, Human* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Herpesvirus+4%2C+Human%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Herpesvirus+4%2C+Human) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41947331/) * Herpesvirus 4, Human* / isolation & purification Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Herpesvirus+4%2C+Human%2Fisolation+and+purification%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Herpesvirus+4%2C+Human
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