Epstein–Barr Virus Association and Prognosis in Taiwanese Hodgkin Lymphoma: A Nationwide Multicenter Study With Comparison to United States Whites

Hodgkin lymphoma (HL) is associated with Epstein-Barr virus (EBV) infection in a subset of cases. We previously showed that the incidence of HL in Taiwan increased ~2.5-fold between 2001 and 2020, particularly among young women with the nodular sclerosis (NS) subtype. In this nationwide multicenter study, we evaluated EBV status in HL to determine its impact on clinicopathologic features and survival outcomes. We found that the proportion of EBV-associated HL in Taiwan declined over the past two decades, from 39% to 27%. EBV-positive frequency exhibited a bimodal age distribution, peaking in children < 10 years (63%) and adults > 70 years (80%), with the lowest frequency in patients 20-29 years (11%). Compared with EBV-negative patients, EBV-positive patients were older (53.5 vs. 32.9 years; p < 0.001), predominantly male (73.1% vs. 48.7%; p < 0.001), more likely to have nodal disease (83.3% vs. 74.2%; p = 0.003) and mixed cellularity histology (37.1% vs. 11.4%; p < 0.001), and had inferior 10-year survival (56.3% vs. 85.7%; p < 0.001). Adverse prognostic factors in HL included older age (> 60 years), B symptoms, non-NS histology, EBV-positivity, advanced-stage disease (Stage III-IV), and a high International Prognostic Score (IPS, 4-7). On multivariate analysis, older age and a high IPS retained prognostic significance. Large registry datasets from Taiwan and the US further demonstrated that survival outcomes have improved over the past two decades. Female patients and those with the NS and nodular lymphocyte-predominant subtypes had significantly better survival. These findings provide insight into the biological impact of EBV in HL and help inform strategies for disease prevention and management.