Discussion of Epidemiologic Studies Assessing the Role of the Epstein-Barr Virus in Hodgkin's Disease

The enigma of Hodgkin's disease etiology has fascinated several generations of researchers. Of particular scientific interest has been the hypothesis that Hodgkin's disease might have an infectious etiology. The paper by Mueller in this issue chronicles the development of the important work of two generations of investigators (herself and Dr. Alfred S. Evans) trying to explicate the role of viruses, particularly the EpsteinBarr virus (EBV), in the causation of this disease. Almost from its first description in 1832 by Thomas Hodgkin, Hodgkin's disease has been suspected of having an infectious agent as its cause [ 1 ]. This idea is not surprising since one of Hodgkin's original seven cases was found to be a case of syphilis and a second case to be questionable tuberculosis when Fox reviewed pathological materials from the cases in 1926 [2]. At the end of the last century, Hodgkin's disease was frequently found in association with tuberculosis, leading Sternberg to conclude that Hodgkin's disease might be an unusual form of tuberculosis [3]. At the turn of the century, the discovery of the Sternberg-Reed cell, which appeared to be pathognomic for Hodgkin's disease, helped greatly in weeding out several diseases which had previously been confused with Hodgkin's disease [3]. The belief that Hodgkin's disease had an infectious cause, however, persisted well into the 1940s. This fact is evidenced by the inclusion of Hodgkin's disease under the category of infectious and parasitic diseases in the Fourth Revision of the International Classification of Causes of Death [4]. The issue of possible transmissibility of Hodgkin's disease was revived in the 1970s by the work of Vianna and his colleagues in Albany, New York [5,6]. They reported an unusual occurrence of Hodgkin's disease involving members of a particular high school class and their direct and indirect contacts. Their report of an aggregate of 31 cases that could be interlinked by personal contact constituted the largest cancer "cluster" reported in the literature. The meaning of this finding was inevaluable statistically, however. As a result, the Albany group did a systematic study of the occurrence of Hodgkin's disease in high schools in the Long Island area of New York State. They found that a child attending a high school where a case of Hodgkin's disease had been in attendance had a twofold to fifteenfold increased risk of developing the disease [7]. A replication of the Long Island study in the greater Boston area failed to confirm Vianna and Polan's findings [8]. Additional studies from the UK and the State of Washington also failed to support the Long Island study's striking findings [9,10].