The role of Epstein-Barr virus in Hodgkin lymphoma
- Richard F Ambinder, MD, PhD
Richard F Ambinder, MD, PhD
- James B Murphy Professor of Oncology
- Johns Hopkins School of Medicine
Hodgkin lymphoma (HL), formerly called Hodgkin's disease, is a neoplasm that arises from germinal center or post-germinal center B cells. HL has a unique cellular composition, containing a minority of neoplastic cells (Reed-Sternberg cells and their variants) in an inflammatory background. It is separated from the other B cell lymphomas based on its unique clinicopathologic features. (See "Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma".)
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, which is spread mainly through saliva between susceptible persons and asymptomatic EBV shedders. The majority of primary EBV infections throughout the world are subclinical. Antibodies to EBV have been demonstrated in all population groups with a worldwide distribution; approximately 90 to 95 percent of adults are EBV-seropositive. (See "Virology of Epstein-Barr virus".)
The pathobiology of HL remains poorly understood. The role of EBV infection in the development of HL will be reviewed here. Further details on the pathogenesis of HL are discussed separately. (See "The Reed-Sternberg cell and the pathogenesis of Hodgkin lymphoma".)
FACTORS SUGGESTING AN ASSOCIATION
Early epidemiologic data suggested that HL develops among persons with a delayed exposure to a ubiquitous infectious agent, Epstein-Barr virus (EBV). The following sections will review data suggesting an association between EBV and HL. Mechanisms thought to be involved in the development of EBV-negative HL are presented separately. (See "The Reed-Sternberg cell and the pathogenesis of Hodgkin lymphoma".)
Association with infectious mononucleosis and EBV — Initial epidemiologic studies that demonstrated an increased risk of HL in patients with a history of infectious mononucleosis were further substantiated by case control studies showing that patients with HL had elevated antibody titers against EBV antigens, which preceded the disease [1-3]. Subsequent studies showed that EBV could be detected in the tumor cells of a subset of patients with HL [4-8]. Finally, in a population-based cohort study of young adults with infectious mononucleosis in Denmark and Sweden, the risk of developing EBV-negative HL after infectious mononucleosis was not increased (relative risk 1.5, 95% CI 0.9-2.5), whereas the risk of developing EBV-positive HL was increased (relative risk 4.0, 95% CI 3.4-4.5), with a median incubation time from mononucleosis to EBV-positive HL of 4.1 years (95% CI 1.8-8.3 years) . In this population, the absolute risk of developing HL after infectious mononucleosis was approximately 1 in 1000.
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- FACTORS SUGGESTING AN ASSOCIATION
- Association with infectious mononucleosis and EBV
- Association with HLA
- Prognostic value of EBV plasma DNA
- PROPOSED MECHANISMS FOR PATHOGENESIS
- Incidence of EBV positivity
- Timing of infection
- Expression of latent membrane proteins
- - LMP1
- - LMP2a