Introduction The impact of South Africa’s high human immunodeficiency virus (HIV) burden on cancer risk is not fully understood, particularly in the context of antiretroviral treatment (ART) availability. We examined national cancer trends and excess cancer risk in people living with HIV (PLHIV) compared to those who are HIV-negative. Methods We used probabilistic record linkage to match cancer records provided by the National Cancer Registry to HIV data provided by the National Health Laboratory Service (NHLS). We also used text search of specific HIV terms from the clinical section of pathology reports to determine HIV status of cancer patients. We used logistic and Joinpoint regression models to evaluate the risk and trends in cancers in PLHIV compared to HIV-negative patients from 2004 to 2014. In sensitivity analysis, we used inverse probability weighting (IPW) to correct for possible selection bias. Results A total of 329,208 cancer cases from public sector laboratories were reported to the NCR from 2004 to 2014 with the HIV status known for 95,279 (28.9%) cancer cases. About 50% of all the female cancer cases ( n = 30,486) with a known status were HIV-positive. PLHIV were at higher risk of AIDS-defining cancers (Kaposi sarcoma [adjusted OR:134, 95% CI:111–162], non-Hodgkin lymphoma [adjusted OR:2.73, 95% CI:2.56–2.91] and, cervix [adjusted OR:1.70, 95% CI:1.63–1.77], conjunctival cancer [adjusted OR:21.5, 95% CI:16.3–28.4] and human papilloma virus (HPV) related cancers (including; penis [adjusted OR:2.35, 95% CI:1.85–2.99], and vulva [adjusted OR:1.94, 95% CI:1.67–2.25]) compared to HIV-negative patients. Analysis using the IPW population yielded comparable results. Conclusion There is need for improved awareness and screening of conjunctival cancer and HPV-associated cancers at HIV care centres. Further research and discussion is warranted on inclusive HPV vaccination in PLHIV.

Background We analysed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with the human immunodeficiency virus (HIV) in South Africa. Methods We used data from the South African HIV Cancer Match study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHR) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µl decrease. Results Of 3,532,266 people living with HIV (PLWH), 15,078 developed cancer. The most common cancers were cervical cancer (4,150 cases), Kaposi sarcoma (2,262 cases), and non-Hodgkin lymphoma (1,060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µl decrease: 1.46, 95% confidence interval [CI] 1.38-1.54), Kaposi sarcoma (aHR 1.23, 95% CI 1.20-1.26), and non-Hodgkin lymphoma (aHR 1.18, 95% CI 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of oesophageal cancer (aHR 1.06, 95 CI 1.00-1.11), but not breast, lung, or prostate cancer. Conclusions Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections.