The role of viruses in the genesis of hodgkin lymphoma

Abstract

Hodgkin lymphoma is a heterogeneous condition. A proportion of cases of classic Hodgkin lymphoma are associated with the Epstein-Barr virus (EBV), a herpesvirus with a worldwide distribution. In these cases, EBV is present in the tumor cells, the Hodgkin and Reed-Sternberg (HRS) cells, and viral genes are expressed. HRS cells lack functional B-cell receptors, and the EBV proteins LMP-1 and LMP-2 appear to play a critical role in rescuing HRS cells, or their precursors, from apoptosis in germinal centers. These, and other data, support the idea that EBV plays a causal role in disease pathogenesis. EBV-associated cases are relatively more common in young children and older adults but make up a smaller proportion of cases in the young adult age-specific incidence peak. In affluent countries approximately one third of cases are EBV-associated, whereas in lower income countries, this proportion can be much higher. Risk factors for EBV-associated Hodgkin lymphoma include infectious mononucleosis, HLA class I genotype, older age, recent EBV infection in early childhood, and material deprivation. In contrast, the majority of adolescent and young adult classic Hodgkin lymphoma cases are EBV-negative. Development of this disease is associated with lack of preschool attendance; this suggests some degree of social isolation in early childhood and has led to speculation that delayed exposure to one or several common pathogens is involved in disease causation. To date, there is no evidence for direct involvement of a single virus in these cases, but it remains possible that early childhood infections play a role in disease pathogenesis.