BACKGROUND: Case-control studies suggested a moderate, but consistent association of hepatitis C virus (HCV) infection with lymphoid tissue malignancies, especially non-Hodgkin lymphoma (NHL). More limited data suggested that hepatitis B virus (HBV) infection may also be associated with NHL. However, prospective studies on the topic are few.

METHODS: A nested case-control study was performed in eight countries participating in the EPIC prospective study. 739 incident cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc and HBsAg was evaluated and conditional logistic regression was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for NHL, MM or HL, and their combination.

RESULTS: Anti-HCV seropositivity among controls in different countries ranged from 0 to 5.3%; HBsAg from 0 to 2.7%; and anti-HBc from 1.9 to 45.9%. Similar non-significant associations were found with seropositivity to HBsAg for NHL (OR=1.78; 95% CI: 0.78-4.04), MM (OR=4.00; 95% CI: 1.00-16.0), and HL (OR=2.00; 95% CI: 0.13-32.0). The association between HBsAg and the combination of NHL, MM and HL (OR=2.21; 95% CI: 1.12-4.33) was similar for cancer diagnosed <3 and >3 years after blood collection. No association was found between anti-HCV and NHL, MM or HL risk, but the corresponding CIs were very broad.

CONCLUSIONS: Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers.Impact: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies.