CN09-02

Immune deficiency offers an informative window through which to examine the infection-cancer relationship. Simply stated, if a cancer is caused by infection, then it is likely to occur at increased rates in people with immune deficiency. The HIV epidemic, and the expansion of organ transplantation programs, have led to the creation of large cohorts with immune deficiency. In this talk, I will review recent findings on cancer occurrence in these populations.

People with HIV are at increased risk for a wide range of cancers, but there has been debate about whether this is due to immune deficiency, or due to exposure to cancer risk factors such as smoking, alcohol intake, and sexually transmitted and blood-borne pathogens. New light has been shed on these relationships by work on cancer in kidney transplant recipients. As transplant recipients have little in common with people with HIV apart from immune deficiency, shared patterns of cancer occurrence would likely be explained by immune deficiency.

We conducted a retrospective cohort study of 28,855 end stage renal disease patients in Australia. Incident cancers diagnosed between 1982 and 2003 were ascertained by record linkage. Standardised incidence ratios (SIRs) were calculated in transplant recipients. Cancer rates were increased after transplantation for all infection-related cancers, including those related to KSHV (KS); EBV (NHL, Hodgkin lymphoma); HPV (anogenital cancers and head and neck cancers); HBV and HCV (liver cancer) and helicobacter pylori (stomach cancer). Rates were not increased for most epithelial cancers common in the general population. We also conducted a meta-analysis comparing cancer risks in population-based studies of solid organ transplant recipients and in people with HIV infection. This revealed that the pattern of increased cancer incidence was strikingly similar in the two populations.

These data suggest that most infection-associated cancers occur at increased rates related to immune deficiency in people with HIV and in transplant recipients. A key question that remains is whether reversal of immune deficiency can reduce cancer risk. Our analysis of cancer risk in people who cease immune suppression because their kidney transplant fails suggests that cancer risk does rapidly return to baseline. In chronic HIV disease, reversal of immune suppression due to treatment is more gradual and less complete, and the increased rates of some but not all infection-related cancers appear to decrease towards normal levels. Describing cancer rates by current level of immune function is an important research priority among people with HIV.

Infection-related cancer is caused by the interplay between immune function and infection. For many of these cancers, the raised risk associated with immune deficiency can be reversed by a return to normal immunity. These findings have implications for the management of long term mild immune deficient states, and also for the prevention of infection-related cancer in the general population.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN09-02.

Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC