Plasmodium falciparum Malaria and Endemic Burkitt Lymphoma: A Systematic Review in IARC Monograph Format with Formal Evaluation for Reclassification from Group 2A to Group 1

Background. Plasmodium falciparum malaria was classified by the International Agency for Research on Cancer (IARC) as a Group 2A agent — probably carcinogenic to humans — for endemic Burkitt lymphoma (eBL) in 2012 (IARC Monograph Volume 104). This classification was made on the basis of limited but suggestive epidemiological evidence and mechanistic plausibility. Since 2012, three critical evidence developments have substantially strengthened the case: (1) a multi-country dose-response case-control study demonstrating a 39% increase in eBL risk per 100 cumulative lifetime P. falciparum infections; (2) a 17-country systematic review and meta-analysis demonstrating a 44% lower eBL incidence following large-scale insecticide-treated net (ITN) deployment; and (3) molecular characterisation of a direct mechanism by which a specific P. falciparum surface ligand induces EBV lytic reactivation in latently infected B cells. Objective. To conduct a systematic review in IARC monograph format and formally evaluate whether the accumulated evidence for P. falciparum as a cause of eBL now meets the IARC criterion of "sufficient evidence of carcinogenicity in humans" required for Group 1...