The Epidemiology of Hodgkin Lymphoma

Abstract

Hodgkin lymphoma (HL) is characterized by a rare multinucleated giant neoplastic cell in tumors largely composed of other nonmalignant immune cells. It is clear that this entity comprises distinct diseases with separate epidemiological patterns, but the precise definition of each is complicated by correlations between the major defining characteristics: age at diagnosis, histopathology, and the presence of Epstein-Barr virus (EBV) genome in the DNA of the neoplastic cells (EBV tumor status). The most common but least understood of these is EBV-negative nodular sclerosis Hodgkin lymphoma (NSHL), a strongly heritable disease of adolescents and young adults, associated with HLA class II and other immune-related genotypes. NSHL is also subject to strong environmental determinates: it dramatically increases in frequency in populations undergoing economic development and consequent social change and is associated with early childhood isolation. A second entity, defined by EBV-positivity in the tumor cells (EBV-positive HL), occurs at the two age extremes and in young adulthood associated with a history of infectious mononucleosis (IM). Moreover, it is predicted by pre-diagnostic elevated levels of specific EBV antibodies and by higher viral load and is linked to specific human leukocyte antigen (HLA) class I alleles, suggesting poor control of primary EBV infection. EBV-positive cHL is highly correlated with the second most common histopathologic subtype, mixed cellularity HL (MCHL), but the existence of incompletely characterized EBV-negative MCHL and EBV-positive NSHL precludes a definitive understanding. A less common and even more familial condition, distinct from “classical” HL, is nodular lymphocyte predominant HL (NLPHL). Here we describe the demographic patterns of the major HL subtypes and the current state of knowledge of the genetic and nongenetic risk factors.