HIV-related cancer risk declines with ART in Botswana and Uganda, but population burden a major concern

Cancer incidence following expansion of HIV treatment in Botswana

Dryden-Peterson S, Medhin H, Kebabonye-Pusoentsi M, Seage GR, 3rd, Suneja G, Kayembe MK, Mmalane M, Rebbeck T, Rider JR, Essex M, Lockman S. PLoS One. 2015 Aug 12;10(8):e0135602. doi: 10.1371/journal.pone.0135602. eCollection 2015.

Background: The expansion of combination antiretroviral treatment (ART) in southern Africa has dramatically reduced mortality due to AIDS-related infections, but the impact of ART on cancer incidence in the region is unknown. We sought to describe trends in cancer incidence in Botswana during implementation of the first public ART program in Africa.

Methods: We included 8479 incident cases from the Botswana National Cancer Registry during a period of significant ART expansion in Botswana, 2003-2008, when ART coverage increased from 7.3% to 82.3%. We fit Poisson models of age-adjusted cancer incidence and counts in the total population, and in an inverse probability weighted population with known HIV status, over time and estimated ART coverage.

Findings: During this period 61.6% of cancers were diagnosed in HIV-infected individuals and 45.4% of all cancers in men and 36.4% of all cancers in women were attributable to HIV. Age-adjusted cancer incidence decreased in the HIV infected population by 8.3% per year (95% CI -14.1 to -2.1%). However, with a progressively larger and older HIV population the annual number of cancers diagnosed remained constant (0.0% annually, 95% CI -4.3 to +4.6%). In the overall population, incidence of Kaposi's sarcoma decreased (4.6% annually, 95% CI -6.9 to -2.2), but incidence of non-Hodgkin lymphoma (+11.5% annually, 95% CI +6.3 to +17.0%) and HPV-associated cancers increased (+3.9% annually, 95% CI +1.4 to +6.5%). Age-adjusted cancer incidence among individuals without HIV increased 7.5% per year (95% CI +1.4 to +15.2%).

Interpretation: Expansion of ART in Botswana was associated with decreased age-specific cancer risk. However, an expanding and aging population contributed to continued high numbers of incident cancers in the HIV population. Increased capacity for early detection and treatment of HIV-associated cancer needs to be a new priority for programs in Africa.

Abstract [1]  Full-text [free] access [2]


 

A population-level evaluation of the effect of antiretroviral therapy on cancer incidence in Kyadondo county, Uganda, 1999-2008.

Mutyaba I, Phipps W, Krantz EM, Goldman JD, Nambooze S, Orem J, Wabinga HR, Casper C. J Acquir Immune Defic Syndr. 2015 Aug 1;69(4):481-6. doi: 10.1097/QAI.0000000000000620.

Background: The introduction of antiretroviral therapy (ART) in the United States and Europe has led to changes in the incidence of cancers among HIV-infected persons, including dramatic decreases in Kaposi sarcoma and non-Hodgkin lymphoma, and increases in Hodgkin lymphoma, liver, and anogenital malignancies. We sought to evaluate whether increasing availability of ART is associated with changing cancer incidence in Uganda.

Methods: Incident cases of 10 malignancies were identified from Kampala Cancer Registry from 1999 to 2008. ART coverage rates for Uganda were abstracted from the Joint United Nations Program on HIV/AIDS reports. Negative binomial and Poisson regression modeled the association between ART coverage and age-adjusted cancer incidence.

Results: ART coverage in Uganda increased from 0% to 43% from 1999 to 2008. With each 10% increase in ART coverage, incidence of Kaposi sarcoma decreased by 5% [incidence rate ratio (IRR) = 0.95, 95% confidence interval: 0.91 to 0.99, P = 0.02] and stomach cancer decreased by 13% [IRR = 0.87 (95% CI: 0.80 to 0.95), P = 0.002]. Conversely, incidence of non-Hodgkin lymphoma increased by 6% [IRR = 1.06 (95% CI: 1 to 1.12), P = 0.05], liver cancer by 12% [IRR = 1.12 (95% CI: 1.04 to 1.21), P = 0.002], prostate cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.10), P = 0.05], and breast cancer by 5% [IRR = 1.05 (95% CI: 1 to 1.11), P = 0.05]. ART coverage was not associated with incidence of invasive cervical cancer, lung, colon, and Hodgkin disease. These findings were similar when restricted to histologically confirmed cases.

Conclusions: Our findings suggest that AIDS-defining malignancies and other malignancies are likely to remain significant public health burdens in sub-Saharan Africa even as ART availability increases.

Abstract access  [3]

Editor’s notes: There is increasing concern about non-communicable diseases, including cancers, in sub-Saharan Africa. The increasing population of people on antiretroviral therapy (ART) may result in increased absolute numbers of people diagnosed with cancer, presenting a major challenge to often under-resourced cancer diagnosis and treatment services. Few African countries have functional cancer registries. This month, we highlight data reported from both Botswanan and Ugandan cancer registries.

The article by Dryden-Petersen et al. presents data from the Botswanan registry from 2003-2008, a time of rapid ART roll-out. Age-adjusted rates of cancer were estimated using population survey denominators which include HIV status. The analysis distinguishes cancers occurring in HIV-positive individuals from those attributable to HIV (includes Kaposi’s sarcoma, non-Hodgkin’s lymphoma and cervical cancer). Kaposi’s sarcoma, cervix and breast cancer were the most commonly-reported cancers. Overall, against a background of increasing age-adjusted incidence of cancers, the age-adjusted incidence in the HIV-positive population decreased compared to an early peak prior to ART implementation. However, given this expanding population of survivors, the absolute numbers of reported cases remained constant. Different cancers had different trends. Cervical cancer, which affects younger women and which increased over the period studied, may be a particular focus as it is common and relatively easy to identify in the early stages.

The article by Mutyaba et al. presents data from the Ugandan cancer registry for Kyadondo county from 1999-2008, similarly a time of rapid ART roll-out. The analysis uses population denominators, and an ecologic analysis to estimate change in cancer incidence by ART coverage for 10 selected cancers, including Kaposi’s sarcoma, invasive cervical cancer and non-Hodgkin’s lymphoma. Although significant differences in the incidence rate of about half of the cancers were observed over this period, the differences per increase of ART coverage (by 10%) were modest.

These data are now somewhat out of date, but despite the limitations of use of routine data (incomplete and biased ascertainment of cancers, HIV status etc) it is clear that the burden of cancers in these two settings is unlikely to decrease and there are major implications for service provision including screening programmes. 

The findings from the two studies are consistent in showing an important decrease in Kaposi’s sarcoma with ART, but an increase in non-Hodgkin’s lymphoma. However the trends for other cancers (cervical, breast, prostate, liver and lung) are in different directions, which may reflect different ascertainment abilities, ART programmatic differences or different methods of data analysis. Overall both studies highlight that cancer is not declining as ART programmes have been rolled out.

Avoid TB deaths [5]
Cancers [6], Comorbidity [7], HIV Treatment [8]
Africa [9]
Botswana [10], Uganda [11]
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