Heterogeneity of risk factors and antibody profiles in Epstein-Barr virus genome-positive and -negative Hodgkin lymphoma

Background. Hodgkin lymphoma (HL) tumors that contain the Epstein-Barr virus (EBV) genome may differ etiologically from EBV-negative HL tumors. Methods. A case-case study examining heterogeneity of risk factors between disease subgroups compared personal characteristics and EBV antibodies between 95 EBV-positive and 303 EBV-negative patients with HL. Results. We confirmed previous associations of EBV-positive HL with older age, male sex, and mixed-cellularity ( MC) histological subtypes. EBV-positive patients were less educated and more likely to have smoked cigarettes and had more prevalent and higher EBV antibody titers, compared with EBV-negative patients. After adjustment for all independent risk factors, those most strongly associated with EBV-positive HL were histological subtypes (odds ratio [OR] for MC vs. nodular sclerosis histology, 3.2; 95% confidence interval [CI], 1.4-7.2), elevated anti viral capsid antigen level (OR, 3.1; 95% CI, 1.6-6.0), and less education (OR, 0.7; 95% CI, 0.5-1.0). Cigarette smoking and a low anti-Epstein- Barr nuclear protein (EBNA) 1: anti-EBNA-2 ratio were also marginally associated with EBV-positive HL. Conclusions. EBV-positive HL is more common among individuals who have markers of diminished cellular immunity and an abnormal EBV antibody response. EBV appears to participate in the etiology of EBV-positive HL but may not be involved in EBV-negative HL.