Ronald LaPorte, University of Pittsburgh, USA Hodgkin’s disease has received considerable attention in the past 3 decades. Remarkable advance have been made in the care for patients who have Hodgkin's disease, less is known about prevention. It is a disease that appears to have a complex interaction of viral, immunologic and genetic susceptibility Ronald LaPorte, University of Pittsburgh, USA

Perhaps the greatest interest is because of the evidence that the disease appears to have many of the characteri stics of an infectious disease. This is important as when the epidemiologic investigations began, it was a time of the shift from infectious diseases to non-communicable diseases. 

In the late 1950s and the early 1960s there was much excitement In the late 1950s and the early 1960s there was much excitement. Epidemiology was being applied to chronic diseases, very strong relationships were being found such as smoking to lung cancer. Burkitt discovered a lymphoma in Africa which clearly had an infectious basis. Hodgkin’s disease appeared to have many of the characteristics of an infectious disease. 

One of the major early questions was whether Hodgkin’s disease was truly a cancer. It appeared to have some of the characteristics but not others. It also has been a major success story as 5 and 10 years remission rates have risen dramatically. 

The disease varies as to the speed of progression from a benign to very aggressive condition which rapidly leads to death. All suggest heterogeneity of the disease. 

The disease can be classified according to several histologic characteristics. These all suggest that the disease may not be one disease, but multiple diseases with different etiologies. Why might this pose a problem to study epidemiologically? 

The incidence rates are quite low, lower than most cancers and most other non-communicable diseases. (WM=White male, WF=White female, NWM= Non white male, NWF=Non white female). 

An extremely fascinating difference appears for the epidemiology of HD depending upon the age at onset. There is a complete reversal of pattern for younger compared with older onset cases. 

The Polio Model has been thought to hold for many diseases such as HD or MS or in fact many of the autoimmune diseases, such as rheumatic fever. With the Polio model, with higher SES the incidence is higher, and the age at onset higher. 

It is postulated, that early exposure in effect “immunizes” against HD, where exposure creates a subclinical infection. In contrast, later exposure is more likely to produce overt manifestations. Low SES areas are thought to produce earlier exposure as sanitary conditions are poorer. 

The sex ratio tells us much about HD The sex ratio tells us much about HD. There is an early peak onset, where males predominate, followed by a reduction of cases where the sex ratios approaches one, followed by a gradual rise upward. This has been taken as 3 different diseases and etiologies of HD which vary by the age at onset and may be sex hormone mediated. 

In the early 1960s there was a marked difference in incidence by religion in Boston NY. There are several possible explanations, the first being the different genetic background of the primarily Irish Catholic and Jewish groups. A second difference is the Jewish groups in the early 1960s had a higher socioeconomic status that the Catholic group. 

HD is strongly related to increased education, which is perhaps the most potent determinant of socioeconomic status. 

It has been speculated that an increase in sibship size would be related to a reduced risk of disease. The reason for this is that with a greater number of brothers and sisters one has, the more likely one is to be exposed to the HD agents. 

The relations vary as a function of when a person develops HD. 

In adults, the education relationship actually is opposite to that of youth onset, suggesting again that there is a different etiology in relationship to the age at onset. 

HD clusters in schools. Thus if one child develops HD in a school, a second child is more like to develop HD, again implying a transmittable agent. 

It is intriguing that the clustering only occurred in people exposed to each other in high school, suggesting that the agent is transmitted somewhat later in life. 

EBV has been implicated as a possible etiologic agent EBV has been implicated as a possible etiologic agent. Several case control studies suggest that there are somewhat higher titers in cases than controls. The problem is that because HD is rare, one has to look at HD cases who have had disease for a long time. The disease itself could affect the likely hood of being exposed, though contact in the health care s system. The immunologic difficulties may also increase the likelihood of raised titers. Also, the problem is that a large percentage of people will have raised titers, thus it is not very specific. Despite all this, there appears to be an association, although it is weak. 

The EBV-HD relationship varies in relationship to the type of disease The EBV-HD relationship varies in relationship to the type of disease. It also likely varies in relationship to host susceptibility. 

There is no relationship to herpes simplex There is no relationship to herpes simplex. It is always important to have a viral agent control, such as Herpes. The reason for this is to see if the rise in titers with EBV is a non-specific reaction, or one specific to the suspected etiologic agent�EBV. 

Several studies have followed people who developed mononucleosis, and EBV. There appears to be an excess mortality of lymphomas in people who had mononucleosis suggest a viral etiology. 

Altered Immunity: Tonsillectomy appears to be associated with an increased risk for HD. 

Altered Immunity: People who are immunosupressed due to transplant are at markedly increased risk for lymphomas. 

There most certainly is a genetic component There most certainly is a genetic component. First degree relatives are at over a 10 fold increased risk of HD. Within family, it may not be environmental as spouses do not appear to have an excess risk. 

Twins are at a marked increased risk for becoming concordant, suggesting a strong genetic component. However, it is not purely a genetic disease as over 90% of the twins do not become concordant. Of interest is when twins become concordant, they develop the type of HD. 

There are strong HLA associations for HD There are strong HLA associations for HD. The actual genetic marker has not been closely worked out.