Defining the Risk of non-AIDS Defining Cancer in HIV+/AIDS Populations in Africa: a Preliminary Step Towards National Planning:
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In 2009, more Africans with HIV infection than ever before received anti-retroviral therapy (ART) (37%, or approximately 4 million people in 2009; 80% receiving it for at least 4 years). This has increased the size of the HIV infected population in Africa and also resulted in many more HIV-infected people reaching the age of 40 years. This is not all good news. In the USA, for example, an increasing burden of HIV-related non-AIDS defining (N-ADC) cancers, such as anal cancer, lung cancer, Hodgkin lymphoma and squamous carcinoma of the conjunctiva has been observed in patients on ART. At present, there is essentially no published information from Africa on this topic, and consequently, INCTR, in discussion with Dr Ullrich from WHO Headquarters and Dr Jean-Marie Dangou, of the WHO African Regional Office, felt that a consultation should be planned to discuss what, if anything, should be done at this time. The consultation was held on February 2nd, 2013, immediately after INCTR’s meetings on Cancer Registries and Pathology, and including experts who had attended both these meetings.

The meeting began with an overview by Dr Sam Mbulaiteye of NCI regarding the pattern and potential pathogenetic mechanisms. Very little is known about the pattern of HIV+ N-ADC cancers in Africa. There appears to be an increase in H.pylori associated stomach cancer in Rwanda, and Dr Nestori reported seeing embryonal carcinomas in th children of HIV+ mothers, but such information is anecdotal at present. With respect to pathogenesis, perhaps immune reconstitution itself could be in part responsible. The risk of Hodgkin lymphoma in HIV+ individuals, for example, is known to increase with rising CD4 count. However, the role of environmental factors, genetic factors, virus subtypes (HIV-1 versus HIV-2), the duration of infection, and the antiretroviral drugs themselves, all potential risk factors, remain unknown. Clearly, much more research on the pathogenesis of each type of cancer is required.

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Dr Max Parkin then reported on the situation with respect to cancer registration. So far, there are few long term time trend studies allowing an evaluation of changes in incidence that may be related to HIV and ART prevalence, although in Harare, the incidence of KS, SCC of the conjunctive, and NHL in young adults, has been decreasing since about 2000. A few cancer registries in Africa do attempt to record the HIV status of registered cases, but the level of completion of this information is very low, and almost certainly biased since those patients for whom the information is available are those that were tested because they were suspected of being HIV positive. The first attempt to link cancer registries with series of HIV+ individuals in Africa was performed in Uganda, where a registry of known HIV positive individuals resident in Kampala and attending the local AIDS support organization was linked to the Kampala Cancer Registry and the risk of cancer in HIV positive subjects estimated, relative to that in the general population.A new large scale linkagestudy of the same type is underway in S. Africa. This is a probabilistic record linkage of five South African HIV cohorts within the IeDEA (International epidemiologic databases to evaluate AIDS) consortium to the National Cancer Registry in the HAART era (2004– 2011). The objectives are to determine the incidence, prevalence and risk factors of AIDS-defining and non-AIDS defining cancers in HIV-infected adults on ART, and to describe the degree of under-underascertainment of cancers in HIV treatment programmes. . The South African study was discussed within the African Cancer Registry Network (AFCRN), which includes 21 members, and a sub group has been established to review opportunities for linkage of established HIV cohorts with cancer registries in a number of countries in East, Central and West Africa,. Linkage is relatively simple (conceptually) provided several identical identifier fields are included in both databases (e.g.,name, ID number, date of birth,sex).
After considerable discussion regarding various approaches to addressing the issue of the fraction of patients with cancer who are HIV+ and how HIV positivity varied in different cancers it was concluded that:
a) There is very little data available from Africa
b) Studies are justified in order to:
• Confirm associations demonstrated in Europe & N. America
• Identify new associations with infection-related cancers?
• Estimate the magnitude of the problem
• Study the effects of ARVs or other confounding factors
c) A systematic review of the availability of possible locations for linkage studies is needed. This involves identifying cohorts of know HIV status (ideally with treatment data) in areas served by a population-based cancer registry that is relatively (at least 70%) complete in case finding.
d) The ethics of performing linkage studies generally needs to be clarified
e) It may be necessary to ask an organization to coordinate the process
f) Some hospitals (eg Kenyatta National Hospital) test all cancer patients for HIV (since it may impact upon their treatment). Such a process would greatly assist the collection of information on unselected cancer casesA policy to ensure that all cases are collected should be in place
g) Some countries may be of particular interest because of their size, or the pre-existence of AIDS networks (e.g., Nigeria)
h) A report with recommendations would be submitted to WHO and further actions decided upon

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