In the combination antiretroviral therapy (ART) era, cancers have become an increasingly important contributor to morbidity and mortality in people infected with HIV . Various factors have been associated with increased cancer risk in this population, including depth and duration of immune suppression [2,3]; levels of circulating viremia [2–4]; high prevalence of oncogenic viruses (e.g. HPV, hepatitis B and C, etc.) [5,6]; frequent exposure to behavioral carcinogens (e.g. alcohol and tobacco) [7–9]; and aging . However, numerous epidemiologic studies have documented declines in AIDS-defining cancers (ADCs), whereas more recent studies have noted a rise in many non-AIDS-defining cancers (NADCs) in this population. In particular, data from the US HIV/AIDS Cancer Match (HACM) Study, led by researchers at the National Cancer Institute, have provided a wealth of information about cancer trends in HIV-infected individuals in the US, yet the fundamental reasons for these changing rates has not been well defined. In this issue of AIDS, Robbins et al.  examine population-level factors as potential explanations for changing cancer trends within the HACM. The authors propose three principal influences on cancer incidence rates in HIV: changes in the demographic structure of the subpopulation itself – aging; changes in cancer incidence in the underlying general population from which the subpopulation hails – the background rate; and changes in the risk of cancer in HIV compared to the general population – changing relative risk.
The findings from this study have important implications not just for the US and other developed countries with a mature HIV epidemic, but they also may help predict future trends in resource-limited settings. A limited number of summaries on current trends  and future projections  of the global cancer burden in the general population are available. However, in resource-limited settings, population-level data on cancer trends in individuals with HIV are almost entirely unavailable. The findings of the study by Robbins et al., combined with global patterns in the general population, may help researchers and clinicians anticipate future trends in cancer in HIV populations worldwide. For example, the changing demographics of the HIV population in the US, mainly an increase in life expectancy due to widespread uptake of highly effective ART, was associated with trends in Kaposi sarcoma (declining), breast and colorectal (not changing), liver (increasing), lung (decreasing), and prostate (increasing). Thus, in the developing world, we might expect that when ART uptake is equally long-term and widespread, it will likely affect cancers that develop at older ages. However, the increased rate of cancer due to aging may be offset by the general health improvement due to ART, whereby the risk of cancer in HIV decreases relative to the general population. This was especially true for ADCs in the US, which all decreased over time in the HIV population and relative to the general population. These declines may also be attributable to the effect of ART on cancer-causing infections, such as human herpes virus 8 (HHV8), or improved screening in the HIV population.
Given the vast need for improvements in cancer screening in many developing countries that likely exceed those in the US during the 1996–2010 study period, changes in screening have the potential to greatly contribute to apparent increases in cancer in the HIV population in the future. Finally, as cancer incidence changes in the general population due to screening, changes in lifestyle, and other important risk factors, the current study finds that this will also contribute to changing patterns in HIV, mainly the NADCs. As in the US, increases in anal and liver cancers can be expected in most settings. In the US, lung cancer was declining in the HIV population along with the general population decline; however, many global settings still have high and increasing tobacco rates, and we therefore anticipate lung cancer incidence to increase until smoking cessation programs affect the population-level exposure to this carcinogen, as we have seen in the US and Europe. Two additional epidemiologic contributors to cancer trends that are not as relevant to the US and many other developed countries, but that will greatly affect background rates and cancer incidence in HIV in several developing countries, are the projected population growth and the transition from infection-associated to lifestyle-associated cancers in the coming decades.
In conclusion, for domestic and international epidemiologists and clinicians focusing on HIV and cancer, the good news from this study is that ART appears to have a significant impact on population-level incidence of ADCs, such that with earlier treatment initiation, as is now recommended in the US and abroad, the number of ADCs should continue to decline over time. Thus, resource-limited countries, where chemotherapy and radiation therapy are largely unavailable, should consider that expanding access and use of ART may be an important additional measure of ADC prevention. In addition, as the HIV population ages and affects cancer risk evaluation of and adherence to current cancer screening guidelines will become even more important for preventing morbidity and mortality in the HIV population.
Conflicts of interest
There are no conflicts of interest.
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