Hepatitis B and C viruses and risk of non-Hodgkin lymphoma: A case-control study in Italy

Background: Hepatitis C virus (HCV) has been consistently associated to non-Hodgkin lymphoma (NHL); conversely, few studies have evaluated a comprehensive serological panel of hepatitis B virus (HBV) in NHL etiology. Methods: We conducted a case-control study in Italy in 1999-2014, enrolling 571 incident, histologically confirmed NHLs and 1004 cancer-free matched controls. Study subjects provided serum for HCV and HBV testing and for HCV RNA. Odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated by logistic regression, adjusting for potential confounders. Results: Circulating HCV RNA was detected in 63 (11.1 %) NHL cases and 35 (3.5 %) controls (OR = 3.51, 95 % CI: 2.25-5.47). Chronic HBV infection (i.e., positive to HBV surface antigen - HBsAg⁺) was found in 3.7 % of cases and 1.7 % of controls (OR = 1.95, 95 % CI: 1.00-3.81); a significantly elevated OR was observed for B-cell NHL (2.11, 95 % CI: 1.07-4.15). People with serological evidence of past HCV or HBV infection, vaccination against HBV, or detectable antibodies against HBV core antigen (anti-HBc⁺) alone were not at increased NHL risk. Conclusions: Our results support a role of chronic HCV infection in NHL in Italy and suggest an involvement of HBV infection. Associations were clearest for B-cell NHL and diffuse large B-cell lymphoma. Prevention and treatment of HCV and HBV infection may diminish NHL incidence, notably in areas with high prevalence of hepatitis viruses infection.