Lymphoid neoplasms and benzene exposure using a revised classification scheme: systematic review and meta-analysis

Lymphoid neoplasms are a diverse group of cancers derived from lymphocytes, with classification recently updated by the 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5). Benzene, a well-known carcinogen, is widely used in industries and environmental exposures vary; however, its association with specific lymphoid neoplasm subtypes remains unclear due to historical classification challenges. This study aimed to clarify the risk of lymphoid neoplasms related to benzene exposure using the updated WHO-HAEM5 framework.A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible studies were comparative human studies evaluating benzene exposure and lymphoid neoplasm risk, with sufficient data for risk estimates. Inclusion criteria specified study designs, participants, exposures and outcomes based on clinical diagnoses. Data were independently extracted by multiple reviewers. The main outcome was risk of lymphoid neoplasms and subtypes analysed by random-effects meta-analysis with heterogeneity and bias assessments.From 1488 records, 95 studies met criteria (65 occupational and 30 environmental exposure). Benzene exposure significantly increased overall lymphoid neoplasm risk (RR 1.26; 95% CI 1.18 to 1.35). B-cell neoplasms showed elevated risk (RR 1.26; 95% CI 1.16 to 1.37), including mature B-cell neoplasms, Hodgkin lymphoma and plasma cell neoplasms. T-cell and natural killer cell neoplasm risk was not significantly increased overall. Occupational exposures conferred higher risks with lower heterogeneity than environmental exposures.Benzene exposure is strongly associated with increased risk of lymphoid neoplasms, particularly B-cell subtypes, supported by the refined WHO-HAEM5 classification reducing heterogeneity. This study underscores the importance of biologically informed disease classification and the need for targeted occupational safety and environmental health policies.The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID: CRD420251063844) .