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MEDICAL BIOLOGY: ON INFECTION AND LYMPHOMA

The following points are made by H. Hjalgrim et al (New Engl. J. Med. 2003 349:1324):

1) Despite the distinctive epidemiologic characteristics of Hodgkin's lymphoma, its cause is unknown.(1) In young adults, the disease may be a rare consequence of exposure to a common infectious agent.(2) There is, for example, a several-fold increase in the risk of Hodgkin's lymphoma after infectious mononucleosis, the typical clinical manifestation of primary Epstein–Barr virus (EBV) infection in adolescence.(3)

2) The suspicion that EBV has a causal role in Hodgkin's lymphoma is further strengthened by the demonstration of EBV antigens in Reed–Sternberg cells from 40 to 50 percent of patients with Hodgkin's lymphomas.(3) However, there is an apparent discrepancy(4): the risk of Hodgkin's lymphoma after infectious mononucleosis is increased primarily among adolescents and young adults,(5) yet EBV can be demonstrated in Reed–Sternberg cells in only a third of patients with Hodgkin's lymphomas in that age group.

3) This apparent inconsistency may be due to bias arising from misclassification caused by the similarity between the symptoms of Hodgkin's lymphoma and those of infectious mononucleosis. It is also possible that the connection between infectious mononucleosis–related EBV infection and Hodgkin's lymphoma in young adults is restricted to a subgroup of lymphomas that contain EBV, or that the virus is lost from Reed–Sternberg cells, the so-called "hit-and-run hypothesis".

4) The authors examined these hypotheses using three population-based cohorts. From their results, the authors conclude: A causal association between infectious mononucleosis–related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.

References (abridged):

1. Mueller NE. Hodgkin's disease. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer epidemiology and prevention. 2nd ed. Oxford, England: Oxford University Press, 1996:893-919

2. Gutensohn N, Cole P. Epidemiology of Hodgkin's disease in the young. Int J Cancer 1977;19:595-604

3. Epstein-Barr virus and Kaposi's sarcoma herpesvirus/human herpesvirus 8. Vol. 70 of IARC monographs on the evaluation of carcinogenic risks to humans. Lyons, France: IARC Press, 1997

4. Mueller NE. Epstein-Barr virus and Hodgkin's disease: an epidemiological paradox. Epstein Barr Virus Rep 1997;4:1-2

5. Hjalgrim H, Askling J, Sorensen P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000;92:1522-1528

New Engl. J. Med. http://www.nejm.org

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