Correspondence
Hodgkin's Disease and HIV Infection
N Engl J Med 1995; 333:65-66July 6, 1995
- Article
To the Editor:
It is generally accepted that Hodgkin's disease in patients infected with the human immunodeficiency virus (HIV) tends to present at an advanced stage and ultimately has a poorer prognosis than in patients not infected with HIV. However, it is not an irrefutable fact that patients infected with HIV ``in particular have an increased risk of Hodgkin's disease,'' as stated by Drs. Diehl and Tesch (Feb. 16 issue).1
That there is an increased incidence of Hodgkin's disease among HIV-infected patients is a controversial statement at best. In a study of women in New York and New Jersey, no increased incidence of Hodgkin's disease was observed from 1976 to 1988, during which time the incidence of AIDS increased substantially.2 A study of 3041 patients with hemophilia observed between 1978 and 1989 also failed to show an increased incidence; no cases of Hodgkin's disease were reported among the 1295 patients who were positive for HIV.3
Although an increased incidence of Hodgkin's disease in HIV-infected patients has been suggested by several epidemiologic studies, this observed trend may be due to one of several factors. For example, the apparent increase may be due to pathological misclassification of non-Hodgkin's lymphomas,4 which have definitively been shown to have an increased incidence in the HIV-infected population. Another confounding phenomenon may be the movement of patients to tertiary care referral centers for the treatment of Hodgkin's disease, which might skew the incidence in the local population being studied. It is also not clear whether one epidemiologic subgroup of HIV-infected patients is more susceptible to Hodgkin's disease.
The relation between Hodgkin's disease and infection with HIV is an interesting one. Perhaps as we continue to increase the longevity of patients infected with HIV, a true increase in the incidence of Hodgkin's disease will emerge. However, it is worth noting that no increased incidence of Hodgkin's disease was observed in 6297 immunosuppressed transplant recipients,5 suggesting that the relation of Hodgkin's disease to underlying immunosuppression is not a strong one. For the time being, the issue warrants further careful epidemiologic studies to document a definitive change in the incidence of Hodgkin's disease among patients infected with HIV, if it in fact exists.
5 ReferencesKevin B. Knopf, M.D.
Gershon Y. Locker, M.D.
Evanston Hospital, Evanston, IL 602011
Diehl V ,Tesch H . Hodgkin's disease -- environmental or genetic? N Engl J Med 1995;332:461-462
Full Text | Web of Science | Medline2
Rabkin CS ,Biggar RJ ,Baptiste MS ,Abe T ,Kohler BA ,Nasca PC . Cancer incidence trends in women at high risk of human immunodeficiency virus (HIV) infection. Int J Cancer 1993;55:208-212
CrossRef | Web of Science | Medline3
Ragni MV ,Belle SH ,Jaffe RA , et al. Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia. Blood 1993;81:1889-1897
Web of Science | Medline4
Glaser SL ,Swartz WG . Time trends in Hodgkin's disease incidence: the role of diagnostic accuracy. Cancer 1990;66:2196-2204
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Hoover R ,Fraumeni JF Jr . Risk of cancer in renal-transplant recipients. Lancet 1973;2:55-57
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Knopf and Locker raise an important issue about Hodgkin's disease. The incidence of Hodgkin's disease among HIV-infected patients is indeed controversial. Although several reports have suggested an association of Hodgkin's disease with AIDS, Hodgkin's disease is not yet considered an AIDS-defining disease in HIV-infected patients. In the largest registry study of AIDS-associated neoplasms, solid tumors did not occur more often than expected. However, the incidence of two types of cancer was significantly increased: Hodgkin's disease and anorectal carcinoma.1 Another group found an excess risk of Hodgkin's disease attributable to HIV infection of 19.3 cases per 100,000 person-years.2 Similarly, an increased incidence of Hodgkin's disease was noted in San Francisco County among men 30 to 49 years of age, a population known to have a high incidence of HIV infection.3 Groups from the United States,1 France,4 and Italy5 observed that the incidence of Hodgkin's disease was higher among intravenous-drug users than among male homosexuals infected with HIV. HIV-infected patients with Hodgkin's disease have relatively high CD4 cell counts, which suggests that the development of Hodgkin's disease may depend on the presence of at least a partially intact immune response.4,6
A major problem is the lack of large epidemiologic studies analyzing the incidence of malignant tumors over a longer period of time. The discrepancies in the published reports could be due to differences in the population of patients and risk groups analyzed (i.e., male vs. female or homosexuals vs. intravenous-drug users). Obviously, pathological misclassification has to be ruled out by a panel of experienced hematopathologists.
Hodgkin's disease has a different natural history and therapeutic outcome in HIV-infected patients and in HIV-negative patients. HIV-positive patients with Hodgkin's disease are likely to present in advanced stages, with extranodal, gastrointestinal, and bone marrow involvement and with B symptoms, and they respond less favorably to cytoreductive therapy. In HIV-negative patients nodular sclerosis is the predominant subtype (about 80 percent), whereas in HIV-positive patients Hodgkin's disease is of the mixed-cellularity subtype in about 40 to 50 percent of cases. The latter subtype is also frequent among older HIV-negative patients. Interestingly, a particularly high prevalence of Epstein-Barr virus was noted in the Reed-Sternberg cells of patients with HIV-associated Hodgkin's disease (11 of 12 patients were positive for Epstein-Barr virus),7 whereas the frequency in HIV-negative patients is 30 to 60 percent.
The question whether HIV infection acts as a cofactor in the pathogenesis of Hodgkin's disease cannot be resolved today. Additional well-designed epidemiologic studies are urgently required to determine whether Hodgkin's disease (or a subtype of the disease) should be considered an AIDS-defining tumor and to analyze the role of the immune system in the pathogenesis or control of this malignant condition.
7 ReferencesV. Diehl, M.D.
H. Tesch, M.D.
University of Cologne, 50924 Cologne, Germany1
Reynolds P ,Saunders LD ,Layefsky ME ,Lemp GF . The spectrum of acquired immunodeficiency syndrome (AIDS)-associated malignancies in San Francisco, 1980-1987. Am J Epidemiol 1993;137:19-30
Web of Science | Medline2
Hessol NA ,Katz MH ,Liu JY ,Buchbinder SP ,Rubino CJ ,Holmberg SD . Increased incidence of Hodgkin disease in homosexual men with HIV infection. Ann Intern Med 1992;117:309-311
Web of Science | Medline3
Medeiros LJ ,Greiner TC . Hodgkin's disease. Cancer 1995;75:357-369
CrossRef | Web of Science | Medline4
Andrieu JM ,Roithmann S ,Tourani JM , et al. Hodgkin's disease during HIV1 infection: the French registry experience. Ann Oncol 1993;4:635-641
Web of Science | Medline5
Carbone A ,Tirelli U ,Vaccher E , et al. A clinicopathologic study of lymphoid neoplasias associated with human immunodeficiency virus infection in Italy. Cancer 1991;68:842-852
CrossRef | Web of Science | Medline6
Rubio R . Hodgkin's disease associated with human immunodeficiency virus infection: a clinical study of 46 cases. Cancer 1994;73:2400-2407
CrossRef | Web of Science | Medline7
Herndier BG ,Sanchez HC ,Chang KL ,Chen YY ,Weiss LM . High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin's disease. Am J Pathol 1993;142:1073-1079
Web of Science | Medline
