Abstract A026: EBV prevalence and overall survival in the MultiEthnic Study of Hodgkin lymphoma (MESH)
Authors: Lam Esther , Wan Jia Y. , Aparicio Jose , Pullarkat Sheeja , Colombo Anthony , Song Joo , Chao Chun , Mejia-Arangure Juan M. , Hernandez Brenda , Jiang Aixiang , Aoki Tomohiro , Allen Pamela , Flowers Christopher , Wang Sophia , Evans Juanita , Chan Owen , Bernal-Mizrachi Leon , Scott David W. , Lim Megan , Svoboda Jakub , Steidl Christian , Siddiqi Imran , Cozen Wendy 
Published: September 2024

Abstract
Classic Hodgkin Lymphoma (CHL) is a B-cell lymphoma characterized by Hodgkin Reed- Sternberg (HRS) cells surrounded by immune cell infiltrates that define histological subtypes. A subset of CHL tumors shows integration of the Epstein-Barr virus (EBV) genome into the HRS cell. EBV tumor positivity is thought to reflect immunocompromised status and has been more common in young and older patients, and non-white patients of lower socioeconomic status. This study aims to examine the distribution of EBV tumor prevalence and determine whether EBV tumor status affects survival, focusing on potential disparities across age, sex, or race/ethnicity. We collected 908 multiethnic cases of formalin-fixed paraffin-embedded tumor blocks of CHL for the MultiEthnic Study of Hodgkin lymphoma (MESH) from multiple sites, including cancer centers, hospitals, and Residual Tissue Repositories. Diagnosis confirmation was conducted by a hematopathologist. Demographic and clinical information were obtained from medical charts and state cancer registries. EBV tumor status was determined using EBER1 in situ hybridization, with EBV+ cases defined by nuclear or cytoplasmic positivity in &gt;5% of HRS cells. We tested associations between EBV tumor status and age at diagnosis (pediatric: &lt;15 years, adolescent/young adult [AYA]: 15-39 years, older adults: 40+ years), sex, race/ethnicity (Hispanic, Black, Non-Hispanic White[NHW], Asian, and Hawaiian/Pacific Islander [HPI]), and histology (Nodular Sclerosis[NS]; Mixed Cellularity[MC]) using χ-squared tests. We tested the effect of EBV on 5-year overall survival (OS), using Kaplan-Meier and multivariable Cox regression analysis adjusted for age at diagnosis, sex, and race/ethnicity. Of the 685 cases diagnosed from 1978 to 2018 with EBV results, about 30% were EBV+. EBV positivity for both NS and MC was higher in pediatric cases (NS: 45%; MC: 90%) and older-aged cases (NS: 29%; MC: 64%) compared to AYA cases (NS: 16%; MC: 39%). AYA had the most CHL cases, mostly EBV−. Males made up more EBV+ cases, with pronounced differences across all age groups (pediatric: 62%; AYA: 24%; older-aged: 46%). EBV positivity varied by race/ethnicity (p=0.002), with the highest prevalence in Hispanics (38%) and the lowest in HPI (10%). EBV+ tumors rose with age in NHW and HPI racial groups, but other racial/ethnic groups showed a decline in prevalence among AYA patients. Adjusted Cox analyses showed no statistically significant association between EBV tumor status and OS (HR=1.08, p=0.744). Stratified analysis showed divergent effects of EBV on OS in AYA and older adult age groups, although the associations were not significant (HR=0.79, p=0.671; HR=1.11, p=0.6842, respectively). Race-specific trends were observed in EBV+ CHL across age groups. Unlike previous reports, we did not observe an association between EBV tumor status and survival. More studies with diverse populations and larger sample sizes are needed to fully grasp the complex interplay between demographic and clinical factors and EBV patterns in CHL tumors across different populations.
Citation Format: Esther Lam, Jia Y. Wan, Jose Aparicio, Sheeja Pullarkat, Anthony Colombo, Joo Song, Chun Chao, Juan M. Mejia-Arangure, Brenda Hernandez, Aixiang Jiang, Tomohiro Aoki, Pamela Allen, Christopher Flowers, Sophia Wang, Juanita Evans, Owen Chan, Leon Bernal-Mizrachi, David W. Scott, Megan Lim, Jakub Svoboda, Christian Steidl, Imran Siddiqi, Wendy Cozen. EBV prevalence and overall survival in the MultiEthnic Study of Hodgkin lymphoma (MESH) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A026.