Skip to main content
NCBI home page
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1987 Jul-Aug;60(4):321–332.

Epidemiologic studies assessing the role of the Epstein-Barr virus in Hodgkin's disease.

N Mueller 1
PMCID: PMC2590239  PMID: 2821703

Abstract

The hypothesis that an infection plays a role in the etiology of Hodgkin's disease (HD) is suggested by both its clinical and histologic features. Its bimodal age-incidence pattern also suggests an infectious process among younger persons. In economically advantaged populations, the first peak occurs among young adults, while in disadvantaged populations, it occurs among children at a much lower frequency. It appears that the age distribution of HD shadows that of susceptibility to common childhood infections, such as the Epstein-Barr virus (EBV); furthermore, that risk of HD is increased among those susceptible to a relatively late infection, in parallel with infectious mononucleosis (IM), and it has been found that people who have had IM have about three times the expected rate of HD. Serologically, there is a consistent association between EBV and HD. As a group, patients have an altered antibody pattern against EBV which suggests chronic reactivation, both following and preceding diagnosis. This altered pattern is common to all age groups. Severity of infection may alter host control among younger people, while diminished cellular immunity with aging may allow similar reactivation among older persons. Whether the EBV plays a direct role or simply reflects the action of a more primary factor is unknown.

Full text

PDF
327

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. COHEN B. M., SMETANA H. F., MILLER R. W. HODGKIN'S DISEASE: LONG SURVIVAL IN A STUDY OF 388 WORLD WAR II ARMY CASES. Cancer. 1964 Jul;17:856–866. doi: 10.1002/1097-0142(196407)17:7<856::aid-cncr2820170706>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  2. Carter C. D., Brown T. M., Jr, Herbert J. T., Heath C. W., Jr Cancer incidence following infectious mononucleosis. Am J Epidemiol. 1977 Jan;105(1):30–36. doi: 10.1093/oxfordjournals.aje.a112352. [DOI] [PubMed] [Google Scholar]
  3. Connelly R. R., Christine B. W. A cohort study of cancer following infectious mononucleosis. Cancer Res. 1974 May;34(5):1172–1178. [PubMed] [Google Scholar]
  4. Correa P., O'Conor G. T. Epidemiologic patterns of Hodgkin's disease. Int J Cancer. 1971 Sep 15;8(2):192–201. doi: 10.1002/ijc.2910080203. [DOI] [PubMed] [Google Scholar]
  5. De Schryver A., Klein G., Henle G., Henle W., Cameron H. M., Santesson L., Clifford P. EB-virus associated serology in malignant disease: antibody levels to viral capsid antigens (VCA), membrane antigens (MA) and early antigens(EA) in patients with various neoplastic conditions. Int J Cancer. 1972 Mar 15;9(2):353–364. doi: 10.1002/ijc.2910090214. [DOI] [PubMed] [Google Scholar]
  6. Evans A. S., Carvalho R. P., Frost P., Jamra M., Pozzi D. H. Epstein-Barr virus infections in Brazil. II. Hodgkin's disease. J Natl Cancer Inst. 1978 Jul;61(1):19–26. doi: 10.1093/jnci/61.1.19. [DOI] [PubMed] [Google Scholar]
  7. Evans A. S., Comstock G. W. Presence of elevated antibody titres to Epstein-Barr virus before Hodgkin's disease. Lancet. 1981 May 30;1(8231):1183–1186. doi: 10.1016/s0140-6736(81)92351-5. [DOI] [PubMed] [Google Scholar]
  8. Evans A. S., Gutensohn N. M. A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings. Int J Cancer. 1984 Aug 15;34(2):149–157. doi: 10.1002/ijc.2910340203. [DOI] [PubMed] [Google Scholar]
  9. Evans A. S., Kirchhoff L. V., Pannuti C. S., Carvalho R. P., McClelland K. E. A case-control study of Hodgkin's disease in Brazil II. Seroepidemiologic studies in cases and family members. Am J Epidemiol. 1980 Nov;112(5):609–618. doi: 10.1093/oxfordjournals.aje.a113033. [DOI] [PubMed] [Google Scholar]
  10. Evans A. S. The spectrum of infections with Epstein-Barr virus: a hypothesis. J Infect Dis. 1971 Sep;124(3):330–337. doi: 10.1093/infdis/124.3.330. [DOI] [PubMed] [Google Scholar]
  11. Goldman J. M., Aisenberg A. C. Incidence of antibody to EB virus, herpes simplex, and cytomegalovirus in Hodgkin's disease. Cancer. 1970 Aug;26(2):327–331. doi: 10.1002/1097-0142(197008)26:2<327::aid-cncr2820260213>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  12. Gotlieb-Stematsky T., Vonsover A., Ramot B., Zaizov R., Nordan U., Aghal E., Kende G., Modan M. Antibodies to Epstein-Barr virus in patients with Hodgkin's disease and leukemia. Cancer. 1975 Nov;36(5):1640–1645. doi: 10.1002/1097-0142(197511)36:5<1640::aid-cncr2820360517>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  13. Gutensohn N. M. Social class and age at diagnosis of Hodgkin's disease: new epidemiologic evidence for the "two-disease hypothesis". Cancer Treat Rep. 1982 Apr;66(4):689–695. [PubMed] [Google Scholar]
  14. Gutensohn N., Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med. 1981 Jan 15;304(3):135–140. doi: 10.1056/NEJM198101153040302. [DOI] [PubMed] [Google Scholar]
  15. Gutensohn N., Cole P. Epidemiology of hodgkin's disease in the young. Int J Cancer. 1977 May 15;19(5):595–604. doi: 10.1002/ijc.2910190502. [DOI] [PubMed] [Google Scholar]
  16. Gutensohn N., Li F. P., Johnson R. E., Cole P. Hodgkin's Disease, tonsillectomy and family size. N Engl J Med. 1975 Jan 2;292(1):22–25. doi: 10.1056/NEJM197501022920105. [DOI] [PubMed] [Google Scholar]
  17. Hallee T. J., Evans A. S., Niederman J. C., Brooks C. M., Voegtly j. H. Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years. Yale J Biol Med. 1974 Sep;47(3):182–195. [PMC free article] [PubMed] [Google Scholar]
  18. Henderson B. E., Dworsky R., Menck H., Alena B., Henle W., Henle G., Terasaki P., Newell G. R., Rawlings W., Kinnear B. K. Case-control study of Hodgkin's disease. II. Herpesvirus group antibody titers and HL-A type. J Natl Cancer Inst. 1973 Nov;51(5):1443–1447. [PubMed] [Google Scholar]
  19. Henle W., Henle G. Epstein-Barr virus-related serology in Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:79–84. [PubMed] [Google Scholar]
  20. Hesse J., Levine P. H., Ebbesen P., Connelly R. R., Mordhorst C. H. A case control study on immunity to two Epstein-Barr virus-associated antigens, and to herpes simplex virus and adenovirus in a population-based group of patients with Hodgkin's disease in Denmark, 1971-73. Int J Cancer. 1977 Jan;19(1):49–58. doi: 10.1002/ijc.2910190108. [DOI] [PubMed] [Google Scholar]
  21. Hilgers F., Hilgers J. An immunofluorescence technique with counterstain on fixed cells for the detection of antibodies to human herpesviruses; antibody patterns in patients with Hodgkin's disease and nasopharyngeal carcinoma. Intervirology. 1976;7(6):309–327. doi: 10.1159/000149972. [DOI] [PubMed] [Google Scholar]
  22. Hirshaut Y., Reagan R. L., Perry S., De Vita V., Jr, Barile M. F. The search for a viral agent in Hodgkin's disease. Cancer. 1974 Oct;34(4):1080–1089. doi: 10.1002/1097-0142(197410)34:4<1080::aid-cncr2820340418>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  23. Johansson B., Klein G., Henle W., Henle G. Epstein-Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. I. Hodgkin's disease. Int J Cancer. 1970 Nov 15;6(3):450–462. doi: 10.1002/ijc.2910060316. [DOI] [PubMed] [Google Scholar]
  24. Kaplan H. S. Hodgkin's disease: unfolding concepts concerning its nature, management and prognosis. Cancer. 1980 May 15;45(10):2439–2474. doi: 10.1002/1097-0142(19800515)45:10<2439::aid-cncr2820451003>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  25. Kvåle G., Høiby E. A., Pedersen E. Hodgkin's disease in patients with previous infectious mononucleosis. Int J Cancer. 1979 May 15;23(5):593–597. doi: 10.1002/ijc.2910230502. [DOI] [PubMed] [Google Scholar]
  26. Lange B., Arbeter A., Hewetson J., Henle W. Longitudinal study of Epstein-Barr virus antibody titers and excretion in pediatric patients with Hodgkin's disease. Int J Cancer. 1978 Nov 15;22(5):521–527. doi: 10.1002/ijc.2910220503. [DOI] [PubMed] [Google Scholar]
  27. Langenhuysen M. M., Cazemier T., Houwen B., Brouwers T. M., Halie M. R., The T. H., Nieweg H. O. Antibodies to Epstein-Barr virus, cytomegalovirus, and Australia antigen in Hodgkin's disease. Cancer. 1974 Aug;34(2):262–267. doi: 10.1002/1097-0142(197408)34:2<262::aid-cncr2820340207>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  28. Levine P. H., Ablashi D. V., Berard C. W., Carbone P. P., Waggoner D. E., Malan L. Elevated antibody titers to Epstein-Barr virus in Hodgkin's disease. Cancer. 1971 Feb;27(2):416–421. doi: 10.1002/1097-0142(197102)27:2<416::aid-cncr2820270227>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  29. Li F. P., Lokich J., Costanza M., Moloney W. C., Hellman S. Hodgkin's disease in the elderly. Lancet. 1973 Apr 7;1(7806):774–774. doi: 10.1016/s0140-6736(73)92167-3. [DOI] [PubMed] [Google Scholar]
  30. Lindahl T., Klein G., Reedman B. M., Johansson B., Singh S. Relationship between Epstein-Barr virus (EBV) DNA and the EBV-determined nuclear antigen (EBNA) in Burkitt lymphoma biopsies and other lymphoproliferative malignancies. Int J Cancer. 1974 Jun 15;13(6):764–772. doi: 10.1002/ijc.2910130605. [DOI] [PubMed] [Google Scholar]
  31. Lokich J. J., Pinkus G. S., Moloney W. C. Hodgkin's disease in the elderly. Oncology. 1974;29(6):484–500. doi: 10.1159/000224931. [DOI] [PubMed] [Google Scholar]
  32. MACMAHON B. Epidemiological evidence of the nature of Hodgkin's disease. Cancer. 1957 Sep-Oct;10(5):1045–1054. doi: 10.1002/1097-0142(195709/10)10:5<1045::aid-cncr2820100527>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  33. MacMahon B. Epidemiology of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1189–1201. [PubMed] [Google Scholar]
  34. Miller R. W., Beebe G. W. Infectious mononucleosis and the empirical risk of cancer. J Natl Cancer Inst. 1973 Feb;50(2):315–321. doi: 10.1093/jnci/50.2.315. [DOI] [PubMed] [Google Scholar]
  35. Mochanko K., Fejes M., Breazavscek D. M., Suarez A., Bachmann A. E. The relation between Epstein-Barr virus antibodies and clinical symptomatology and immunodeficiency in patients with Hodgkin's disease. Cancer. 1979 Dec;44(6):2065–2070. doi: 10.1002/1097-0142(197912)44:6<2065::aid-cncr2820440617>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  36. Muñoz N., Davidson R. J., Witthoff B., Ericsson J. E., De-Thé G. Infectious mononucleosis and Hodgkin's disease. Int J Cancer. 1978 Jul 15;22(1):10–13. doi: 10.1002/ijc.2910220104. [DOI] [PubMed] [Google Scholar]
  37. Newell G. R. Etiology of multiple sclerosis and Hodgkin's disease. Am J Epidemiol. 1970 Feb;91(2):119–122. doi: 10.1093/oxfordjournals.aje.a121119. [DOI] [PubMed] [Google Scholar]
  38. Nilsson K., Klein G. Phenotypic and cytogenetic characteristics of human B-lymphoid cell lines and their relevance for the etiology of Burkitt's lymphoma. Adv Cancer Res. 1982;37:319–380. doi: 10.1016/s0065-230x(08)60886-6. [DOI] [PubMed] [Google Scholar]
  39. O'Conor G. T., Correa P., Christine B., Axtell L., Myers M. Hodgkin's disease in Connecticut: histology and age distribution. Natl Cancer Inst Monogr. 1973 May;36:3–8. [PubMed] [Google Scholar]
  40. Pagano J. S., Huang C. H., Levine P. Absence of Epstein-Barr viral DNA in Amercian Burkitt's lymphoma. N Engl J Med. 1973 Dec 27;289(26):1395–1399. doi: 10.1056/NEJM197312272892604. [DOI] [PubMed] [Google Scholar]
  41. Rocchi G., Tosato G., Papa G., Ragona G. Antibodies to Epstein-Barr virus-associated nuclear antigen and to other viral and non-viral antigens in Hodgkin's disease. Int J Cancer. 1975 Aug 15;16(2):323–328. doi: 10.1002/ijc.2910160216. [DOI] [PubMed] [Google Scholar]
  42. Rosdahl N., Larsen S. O., Clemmesen J. Hodgkin's disease in patients with previous infectious mononucleosis: 30 years' experience. Br Med J. 1974 May 4;2(5913):253–256. doi: 10.1136/bmj.2.5913.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Shope T. C., Khalifa A. S., Smith S. T., Cushing B. Epstein-Barr virus antibody in childhood Hodgkin's disease. Am J Dis Child. 1982 Aug;136(8):701–703. doi: 10.1001/archpedi.1982.03970440045012. [DOI] [PubMed] [Google Scholar]
  44. Silverberg E., Lubera J. Cancer statistics, 1987. CA Cancer J Clin. 1987 Jan-Feb;37(1):2–19. doi: 10.3322/canjclin.37.1.2. [DOI] [PubMed] [Google Scholar]
  45. Smithers D. W. Hodgkin's disease: one entity or two? Lancet. 1970 Dec 19;2(7686):1285–1287. doi: 10.1016/s0140-6736(70)92245-2. [DOI] [PubMed] [Google Scholar]
  46. Temple J. J., Andes W. A. AIDS and Hodgkin's disease. Lancet. 1986 Aug 23;2(8504):454–455. doi: 10.1016/s0140-6736(86)92155-0. [DOI] [PubMed] [Google Scholar]
  47. Ten Napel C. H., The T. H., Van Egten-Bijker J., de Gast G. C., Halie M. R., Langenhuysen M. M. Discordance of Epstein-Barr Virus (EBV) specific humoral and cellular immunity in patients with malignant lymphomas: elevated antibody titres and lowered in vitro lymphocyte reactivity. Clin Exp Immunol. 1978 Dec;34(3):338–346. [PMC free article] [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES