Human immunodeficiency virus infection and cancer
Newton R., Beral V., Weiss R.
Infectious agents are a significant and theoretically preventable cause of cancer. Therefore, the identification of additional cancers with an infectious aetiology has important public health implications. There is evidence that immunosuppression leads to the selective development of certain cancers that are known or thought to be caused by infections. The fact that millions of people are now infected with HIV has provided an unprecedented opportunity to investigate the role of the immune system in the aetiology of cancer, as well as possibly identifying new cancers with an infectious cause. There is good evidence that immunosuppression associated with HIV infection increases the risk of Kaposi's sarcoma, non-Hodgkin's lymphoma, squamous cell carcinoma of the conjunctiva, Hodgkin's disease and leiomyosarcoma in children. Most of these cancers are thought to be caused by specific human herpesviruses. Few other cancers show a large increase in risk associated with HIV infection, although relatively small increases for rare tumours cannot be excluded. The available evidence suggests that invasive cervix cancer and hepatocellular cancer, both of which are known to be caused by infectious agents, do not appear to be increased markedly in people with HIV or AIDS. There is mounting evidence that causal factors in the aetiology of HIV associated cancers are similar to those for the same cancers occurring in the general population. Similarly, the personal characteristics of those who develop a specific cancer are similar among HIV infected and HIV uninfected individuals with t he same tumour. The main determinant of Kaposi's risk is known to be infection with HHV8, and this infection is identified in both HIV seropositive and HIV seronegative adults and children (Boshoff, this volume). Case-control studies from Uganda show that the personal characteristics of those who develop Kaposi's sarcoma show striking similarities between those with and without HIV infection and that these individuals are distinguished by features of wealth and high social status (Ziegler et al, 1997, 1998). Viral genomes and viral gene products of the Epstein-Barr virus have been found in tumour tissue of subjects with non-Hodgkin's lymphoma, but they tend to be found more often in immunosuppressed people than in the immunocompetent. The implications of this are unclear, but there is evidence that the viral load of both HHV8 ad EBV increases with increasing levels of immune impairment (Boshoff, this volume, Rickinson et al, 1997), which in turn would make the virus easier to detect with current technology. This has important implications for research on HIV associated cancers. It would seem probable that the same factors that are important in the aetiology of cancer in those with HIV infection are also important in the aetiology of cancer in those without HIV infection. Furthermore, an infectious cause is likely to be easier to identify in the immunosuppressed than in the immunocompetent. Therefore, the study of HIV associated cancers is likely to be of relevance to the population as a whole. There may be other cancers whose incidence is increased in association with HIV infection, but, if so, they are probably rare, and the associated relative risks are not likely to be large. Further research is needed to clarify which other tumours are increased in people with HIV and the magnitude of the associated relative risk in those that are. In particular, there is a need for further record linkage studies in populations where HIV prevalence is low and for further case-control studies in populations where HIV prevalence is high. In the mean time, because the number of specific cancers reported in any single study tends to be small, it would be valuable to combine the results from existing studies. Understanding why immunosuppression increases the risk of certain, but not all, cancers that are known to be caused by infectious agents may lead to important insights into the carcinogenic process. In addition, understanding why certain viruses can be found in association with tumours in HIV seropositive subjects, but not in similar tumours in HIV seronegative subjects, may aid our understanding of the role of these infections in the aetiology of cancer in the general population. With the prospect of improved survival for HIV infected people and the wider relevance of such research it will become increasingly important to known more about the risk of cancer in these individuals.