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Background Old age is an important risk factor for developing cancer, but few data exist on this association in people with human immunodeficiency virus (HIV, PWH) in sub-Saharan Africa. Methods The South African HIV Cancer Match study is a nationwide cohort of PWH based on a linkage between HIV-related laboratory records from the National Health Laboratory Service and cancer diagnoses from the National Cancer Registry for 2004–2014. We included PWH who had HIV-related tests on separate days. Using natural splines, we modeled cancer incidence rates as a function of age. Results We included 5 222 827 PWH with 29 580 incident cancer diagnoses—most commonly cervical cancer (n = 7418), Kaposi sarcoma (n = 6380), and breast cancer (n = 2748). In young PWH, the incidence rates for infection-related cancers were substantially higher than for infection-unrelated cancers. At age 40 years, the most frequent cancer was cervical cancer in female and Kaposi sarcoma in male PWH. Thereafter, the rates of infection-unrelated cancers increased steeply, particularly among male PWH, where prostate cancer became the most frequent cancer type at older age. Whereas Kaposi sarcoma rates peaked at 34 years (101/100 000 person-years) in male PWH, cervical cancer remained the most frequent cancer among older female PWH. Conclusions Infection-related cancers are common in PWH in South Africa, but rates of infection-unrelated cancers overtook those of infection-related cancers after age 54 years in the overall study population. As PWH in South Africa live longer, prevention and early detection of infection-unrelated cancers becomes increasingly important. Meanwhile, control strategies for infection-related cancers, especially cervical cancer, remain essential.

Summary Background Literature on cancer in adolescents and young adults (AYA; aged 15–24 years) living with HIV is scarce. We studied cancer incidence in AYA living with HIV in South Africa between 2004 and 2014. Methods In this nationwide cohort study, we included individuals between 15 and 24 years old who had at least two HIV-related laboratory measurements on separate days between Jan 1, 2004, and Dec 31, 2014, recorded in the National Health Laboratory Service database. We used privacy-preserving probabilistic record linkage methods to identify HIV-related laboratory records that most likely belonged to the same individual and to then link these individuals to cancer diagnoses from the National Cancer Registry. We computed incidence rates for the most common cancers in AYA living with HIV, and we assessed associations between these cancers and sex, age, calendar year, and CD4 cell count using Cox proportional hazards models and adjusted hazard ratios (aHRs). Findings We included 782 454 AYA living with HIV (698 066 [89·2%] women) with 1 428 114 person-years of follow-up. Of those, 867 developed incident cancer (incidence rate 60·7 per 100 000 person-years), including 429 who developed Kaposi sarcoma (30·0 per 100 000 person-years), 107 non-Hodgkin lymphoma (7·5 per 100 000 person-years), 48 Hodgkin lymphoma (3·4 per 100 000 person-years), 45 cervical cancer (3·4 per 100 000 woman-years), and 32 leukaemia (2·2 per 100 000 person-years). Kaposi sarcoma was more common in the 20–24 year age group than the 15–19 year age group (aHR 1·39, 95% CI 1·03–1·86). Male sex was associated with higher rates of Kaposi sarcoma (2·06, 1·61–2·63), non-Hodgkin lymphoma (3·17, 2·06–4·89), Hodgkin lymphoma (4·83, 2·61–8·93), and leukaemia (unadjusted HR 5·90, 95% CI 2·87–12·12). Cancer rates decreased over the study period, driven by declining Kaposi sarcoma rates. Lower baseline CD4 cell counts were associated with higher rates of Kaposi sarcoma, cervical cancer, non-Hodgkin lymphoma, and Hodgkin lymphoma, but not leukaemia. Interpretation Infection-related cancers were the most common cancer types in AYA living with HIV in South Africa, and their incidence rates increased with lower CD4 cell counts. Therefore, innovative strategies to maintaining high CD4 cell counts are needed to reduce the cancer burden in this vulnerable population. Funding US National Institutes of Health and Swiss National Science Foundation.

Old age is an important risk factor for developing cancer, but few data exist on this association in people with HIV (PWH) in sub-Saharan Africa.The South African HIV Cancer Match study is a nationwide cohort of PWH based on a linkage between HIV-related laboratory records from the National Health Laboratory Services and cancer diagnoses from the National Cancer Registry for 2004-2014. We included PWH who had HIV-related tests on separate days. Using natural splines, we modelled cancer incidence rates as a function of age.We included 5,222,827 PWH with 29,580 incident cancer diagnoses - most commonly cervical cancer (n = 7418), Kaposi sarcoma (n = 6380), and breast cancer (n = 2748). In young PWH, the incidence rates for infection-related cancers were substantially higher than for infection-unrelated cancers. At age 40 years, the most frequent cancer was cervical cancer in female and Kaposi sarcoma in male PWH. Thereafter, the rates of infection-unrelated cancers increased steeply, particularly among male PWH, where prostate cancer became the most frequent cancer type at older age. While Kaposi sarcoma rates peaked at 34 years (101/100,000 person-years) in male PWH, cervical cancer remained the most frequent cancer among older female PWH.Infection-related cancers are common in PWH in South Africa, but rates of infection-unrelated cancers overtook those of infection-related cancers after age 54 years in the overall study population. As PWH in South Africa live longer, prevention and early detection of infection-unrelated cancers becomes increasingly important. Meanwhile, control strategies for infection-related cancers, especially cervical cancer, remain essential.

Kaposi Sarcoma (KS) is endemic in several countries in Southern and Eastern Africa, relatively rare worldwide but a leading cancer among people living with HIV. KS has always been more common in adult males than females. We assessed the prevalence of known cancer modifying factors (parity, hormonal contraceptive use in females, sex-partners, smoking and alcohol consumption in both sexes), and their relationship to KS, and whether any of these could account for the unequal KS sex ratios. We calculated logistic regression case-control adjusted odds ratios (ORadj), and 95% confidence intervals (95%CI), between KS and each of the modifying factors, using appropriate comparison controls. Controls were cancer types that had no known relationship to exposures of interest (infection or alcohol or smoking or contraceptive use). The majority of the 1275 KS cases were HIV positive (97%), vs. 15.7% in 10,309 controls. The risk of KS among those with HIV was high in males (ORadj=116.70;95%CI=71.35–190.88) and females (ORadj=93.91;95%CI=54.22–162.40). Among controls, the prevalence of smoking and alcohol consumption was five and three times higher in males vs. females. We found a positive association between KS and heavy vs. non-drinking (ORadj=1.31;95%CI=1.03–1.67), and in current heavy vs. never smokers (ORadj=1.82;95%CI=1.07–3.10). These associations remained positive for alcohol consumption (but with wider CIs) after stratification by sex, and restriction to HIV positive participants. We found no evidence of interactions of smoking and alcohol by sex. Smoking and alcohol consumption may provide a possible explanation for the KS sex differences, given both exposures are more common in men, but confounding and bias cannot be fully ruled out. The role smoking and alcohol play in relation to viral loads of HIV/KSHV, differences in immunological responses or other genetic differences between males and females warrant further studies.

Background We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) 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 (aHRs) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µL decrease. Results Of 3 532 266 PLWH, 15 078 developed cancer. The most common cancers were cervical cancer (4150 cases), Kaposi sarcoma (2262 cases), and non-Hodgkin lymphoma (1060 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 esophageal 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.

We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR-HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random-effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme-linked immunosorbent assay-based assays had a sensitivity of 18% for detecting CIN2+ (95% confidence interval [CI]: 15-21) and a specificity of 96% (95% CI: 92-98), for slot-blot, sensitivity was 28.9% (95% CI: 23.3-35.1) and specificity was 72% (95% CI: 66.6-77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 16% (95% CI: 8.45-28.6) and specificity was 98% (95% CI: 97-99) for detecting invasive cervical cancer. HR-HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point-of-care screening tests.

The South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The SAM Study's overarching goal is to inform cancer prevention and control programmes in PLWH in the era of antiretroviral treatment in South Africa.PLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS.The SAM cohort currently includes 5 248 648 PLWH for the period 2004 to 2014; 69% of these are women. The median age at cohort entry was 33.0 years (IQR: 26.2-40.9). The overall cancer incidence in males and females was 235.9 (95% CI: 231.5 to 240.5) and 183.7 (181.2-186.2) per 100 000 person-years, respectively.Using data from the SAM Study, we examined national cancer incidence in PLWH and the association of different cancers with immunodeficiency. Cancers with the highest incidence rates were Kaposi sarcoma, cervix, breast, non-Hodgkin's lymphoma and eye cancer.The SAM Study is a unique, evolving resource for research and surveillance of malignancies in PLWH. The SAM Study will be regularly updated. We plan to enrich the SAM Study through record linkages with other laboratory data within the NHLS (eg, tuberculosis, diabetes and lipid profile data), mortality data and socioeconomic data to facilitate comprehensive epidemiological research of comorbidities among PLWH.

Kaposi’s sarcoma (KS) has become a common AIDS-defining cancer in sub-Saharan Africa. Kaposi’s sarcoma-associated human herpesvirus strongly modulated by HIV-related immune suppression are the principal causes of this cancer. No other risk factors have been identified as playing a strong role. HIV prevention programs and good coverage of antiretroviral therapy (ART) in developed countries resulted in a remarkable decline in HIV-KS incidence and better KS prognosis. By contrast, in sub-Saharan Africa, population ART rollout has lagged, but clinical studies have shown positive results in reduction of KS incidence and better KS prognosis. However, the effect of ART rollout in relation to population KS incidence is unclear. We describe the incidence of KS in sub-Saharan Africa, in four time-periods, (1) before 1980 (before HIV/AIDS era); (2) 1981–2000 (early HIV/AIDS era, limited or no ART coverage); (3) 2001–2010 (early ART coverage period); and (4) 2011–2016 (fair to good ART coverage period). We used KS incidence data available from WHO-International Agency for Research on Cancer (IARC) publications and the Africa Cancer Registry Network. National HIV prevalence and ART coverage data were derived from UNAIDS/WHO. A rapid increase in KS incidence was observed throughout sub-Saharan Africa as the HIV epidemic progressed, reaching peak incidences in Period 2 (pre-ART rollout) of 50.8 in males and 20.3 per 100 000 in females (Zimbabwe, Harare). The overall unweighted average decline in KS incidence between 2000 and 2010 and 2011–2016 was 27%, but this decline was not statistically significant across the region. ART rollout coincides with a decline in KS incidence across several regions in sub-Saharan Africa. The importance of other risk factors such as reductions in HIV incidence could not be ascertained.

Background In populations with high rates of human immunodeficiency virus (HIV)-coinfection, the nature of the relationship between human papillomavirus (HPV)-16 and -18 (L1, E6 and E7) antibodies and cervical cancer is still uncertain. We measured the association between seropositivity to HPV (L1, E6 and E7) proteins and cervical cancer among black South African women with and without HIV co-infection. Methods We used questionnaire data and serum collected from consecutively recruited patients with a newly diagnosed cancer from the Johannesburg Cancer Study from 1346 cervical cancer cases and 2532 controls (diagnosed with other non-infection related cancers). Seropositivity to HPV proteins was measured using a multiplex serological assay based on recombinant glutathione S-transferase (GST) fusion proteins. We measured associations between their presence and cervical cancer using unconditional logistic regression models and evaluated the sensitivity and specificity of these HPV biomarkers. Results Among controls, HIV-negative women from rural areas compared to urban had significantly higher HPV seroprevalence, HPV16 E7 (8.6% vs 3.7%) and HPV18 E7 (7.9% vs 2.0%). HPV16 E6 and E7 antibodies were positively associated with cervical cancer in HIV-positive (Adjusted Odds Ratio (AOR) = 33; 95% CI 10–107) and HIV-negative women (AOR = 97; 95% CI 46–203). In HIV-positive women, HPV E6/E7 antibodies had low sensitivity (43.0%) and high specificity (90.6%) for cervical cancer detection. In HIV-negative women, HPV E6/E7 antibodies sensitivity was 70.6% and specificity was 89.7%. Conclusions Our data show that HPV (L1, especially E6 and E7) antibody positivity is associated with cervical cancer in both HIV-positive and HIV-negative women. Nonetheless, being HIV-positive plays an important role in the development of cervical cancer.

AimsTo describe the incidence and epidemiology of conjunctival squamous cell carcinoma (CSCC) in South Africa over a 25-year period (1994–2018), with particular reference to the HIV epidemic.MethodsIncident cases of histologically diagnosed CSCC were identified from the pathology-based South African National Cancer Registry. Crude and direct age-standardised incidence rates (ASIRs) per 100 000 persons (Segi World Standard Population) were calculated using national population statistics and compared by age, sex and ethnicity. Trends in the incidence and demographic features of CSCC were described and analysed. Incidence rates were compared with national HIV-related statistics for the same time period.ResultsIn total, there were 9016 reported CSCC cases (women: 56.6%, black: 86.8%, mean age: 41.5 years). The overall ASIR was 0.78 per 100 000. Two distinct epidemiological patterns were identified: (1) older white men, and (2) younger black women. There was a sixfold increase in CSCC incidence rates between 1994 and 2009 with a corresponding shift from the first to the second disease profile. Despite rising HIV seroprevalence, CSCC incidence rates have declined since 2009. A strong ecological correlation (r=0.96) between CSCC incidence and widespread antiretroviral therapy (ART) provision was identified.ConclusionThis study highlights the evolving trends and disease burden of CSCC in South Africa. Widespread ART provision is ecologically correlated with declining CSCC rates over the last decade. These findings are in keeping with reported trends for other HIV-related cancers and have important implications for future incidence studies and public health policy.

Background: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures. Methods: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt). Findings: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28-49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial Rt was 2.08 (95% confidence interval (CI): 1.71-2.51). Interpretation: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces. Funding Statement: South African National and provincial health departments. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: Surveillance activities for NMC including SARS-COV-2 infection are conducted by the NICD according to National Health Act Regulations. Publication of surveillance data in the peer-reviewed literature was approved by the University of the Witwatersrand Human Research Ethics Committee (Medical) protocol M160667.

Background: Privacy-preserving probabilistic record linkage (PPPRL) methods were developed and applied in high-income countries to link records within and between organizations under strict privacy protections. PPPRL has not yet been used in African settings.Methods: We used HIV-related laboratory records from National Health Laboratory Services (NHLS) in South Africa to construct a cohort of HIV-positive patients and link them to the National Cancer Registry (NCR) with PPPRL. The study was restricted to Gauteng province from 2004 to 2014. We used records with national IDs (gold standard) to determine precision, recall, and f-measure of the linkages. We included all patients with ≥ 2 HIV-related lab records measured in the cohort and assessed the number of cancers diagnosed in people living with HIV (PLWH).Results: We included 11,480,118 HIV-related laboratory records and 664,869 cancer records in the linkage. We included 1,173,908 persons in the HIV cohort; 66.6% were female and median age at first HIV-related lab test was 33.9 years (IQR 27.4-41.3). Of the patients in the cohort, 26,348 were diagnosed with at least one cancer and 8,329 of these cancers were diagnosed before or on the date of the patient’s first HIV-related record; 18,019 were diagnosed after their first HIV-related record. For all linkages, precision, recall, and f-measures were high.Conclusion: Our study showed it is feasible to use PPPRL in an African setting to link routinely collected health records from different data sources and create a longitudinal HIV cohort with cancer outcomes while strictly protecting patient privacy. This work served as the foundation to create a nationwide population-based cohort including all South African provinces which will be used to inform cancer control programs.

ObjectiveTo determine the spectrum of cancers in AYAs living with HIV in South Africa compared to their HIV negative peers.DesignCross sectional study with cancer data provided by the National Cancer Registry and HIV data from the National Health Laboratory Service.Setting and participantsThe NHLS is the largest provider of pathology services in the South African public sector with an estimated coverage of 80%. The NCR is a division of the NHLS. We included AYAs (aged 10-24 years) diagnosed with cancer by public health sector laboratories between 2004 and 2014 (n=8 479). We included 3 672 in the complete case analysis.Primary and secondary outcomesWe used linked NCR and NHLS data to determine the spectrum of cancers by HIV status in AYAs. We also used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex (as appropriate), ethnicity, and calendar period. Due to the large proportion of unknown HIV status we also imputed (post-hoc) the missing HIV status.ResultsFrom 2004-2014, 8 479 AYAs were diagnosed with cancer, HIV status was known for only 45% (n=3812); of those whose status was known, about half were HIV positive (n=1853). AYAs living with HIV were more likely to have Kaposi’s sarcoma (adjusted odds ratio (aOR) 218, 95% CI 89.9-530), cervical cancer (aOR 2.18, 95% CI 1.23-3.89), non-Hodgkin’s lymphoma (aOR 2.12, 95% CI 1.69-2.66), and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27-5.86). About 44% (n=1 062) of AYAs with HIV related cancers had not been tested for HIV, though they were very likely to have the disease.ConclusionsCancer burden in AYAs living with HIV in South Africa could be reduced by screening young women for cervical cancer and vaccinating them against human papilloma virus (HPV) infection.Strength and limitationsThis is the first nationwide study in South Africa to compare the distribution of cancers in adolescents and young adults (AYAs) by HIV status.The record linkage and the additional results determined from the text mining process ensured that we extracted the maximum available HIV results.We assumed a CD4 count test indicates being HIV positive but CD4 testing maybe performed for other reasonsSince this was a population of only AYAs diagnosed with cancer, the odds ratios could be overestimated or underestimated depending on the frequency of the cancer

PURPOSE OF REVIEW Historically, conjunctival cancer has been associated with HIV particularly in sub-Saharan Africa. The human papilloma virus (HPV) has been implicated as a potential causative agent without conclusive evidence. This review covers recent evidence of the epidemiology, diagnosis and treatment of conjunctival cancer in people living with HIV (PLWH). RECENT FINDINGS HIV infection has been attributed to 33% of squamous cell carcinoma of the conjunctiva in sub-Saharan Africa. Although clear evidence of the effect of immunodeficiency on conjunctival cancer risk has been demonstrated, the role of HPV on conjunctival cancer development is still unclear. Biomarkers such as the p16 protein are not always indicative of HPV infection. The Epstein-Barr virus (EBV) might potentially be another infectious agent of interest in the development of conjunctival cancer. There is some evidence of increased conjunctival cancer recurrence post treatment as well as increased probability of metastasis in PLWH. SUMMARY Immunodeficiency increases the risk of conjunctival cancer in PLWH. Symptomatic screening of conjunctival cancer in PLWH should be encouraged. Research on HPV involvement should remain a priority and EBV considered as another etiologic agent of interest. More studies on treatment modalities in PLWH should be considered.

BackgroundSouth Africa (SA) has experienced a rapid transition in the Human Development Index (HDI) over the past decade, which had an effect on the incidence and mortality rates of colorectal cancer (CRC). This study aims to provide CRC incidence and mortality trends by population group and sex in SA from 2002 to 2014.MethodsIncidence data were extracted from the South African National Cancer Registry and mortality data obtained from Statistics South Africa (STATS SA), for the period 2002 to 2014. Age-standardised incidence rates (ASIR) and age-standardised mortality rates (ASMR) were calculated using the STATS SA mid-year population as the denominator and the Segi world standard population data for standardisation. A Joinpoint regression analysis was computed for the CRC ASIR and ASMR by population group and sex.ResultsA total of 33,232 incident CRC cases and 26,836 CRC deaths were reported during the study period. Of the CRC cases reported, 54% were males and 46% were females, and among deaths reported, 47% were males and 53% were females. Overall, there was a 2.5% annual average percentage change (AAPC) increase in ASIR from 2002 to 2014 (95% CI: 0.6–4.5,p-value p-value p-value p-value ConclusionsThe disparities in the CRC incidence and mortality trends may reflect socioeconomic inequalities across different population groups in SA. The rapid increase in CRC trends among the Black population group is concerning and requires further investigation and increased efforts for cancer prevention, early screening and diagnosis, as well as better access to cancer treatment.

Purpose: The South African HIV Cancer Match Study (SAM) is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PWLH retrieved by National Health Laboratory Services (NHLS) and cancer registry data from the National Cancer Registry. SAM aims to study the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The overarching goal of SAM is to inform cancer prevention and control programmes in children and adults living with HIV in the era of antiretroviral treatment in South Africa.Participants: The SAM study is a national cohort of PLWH (both adults and children) who accessed HIV care in public sector facilities from 2004 – 2014 and had HIV diagnostic or monitoring laboratory tests from NHLS.Findings to date: The SAM cohort includes 5 248 648 PLWH; 69% of these are women. The median age at cohort entry is 33.0 years (interquartile range 26.2 - 40.9). Using SAM, we examined national cancer trends in PLWH and the association of different cancers with immunodeficiency. While the risk of Kaposi sarcoma has declined, the risk of conjunctival cancer and HPV-related anogenital cancers (cervical, anal, vulvar, and penile cancers) continues to rise, despite the widespread availability of antiretroviral treatment. Future plans: An update of the SAM cohort to include more recent data is underway. SAM also has the potential to be enriched through record linkage with other laboratory data within the NHLS (such as tuberculosis, diabetes, and lipid profile data), mortality data and socioeconomic data allowing holistic epidemiological research of co-morbidities with HIV. The SAM cohort is a unique resource for research and surveillance of malignancies in PLWH.

Background: The mechanisms linking the human immunodeficiency virus (HIV) to cancer are not fully understood. We analysed associations between immunodeficiency and the incidence of various infection-related and infection-unrelated cancers in a large cohort of people living with HIV (PLWH).Methods: We used data from the South African HIV Cancer Match (SAM) study which is the result of probabilistic record linkage between HIV laboratory measurements provided by the National Health Laboratory Services and cancer records from the National Cancer Registry in South Africa. We classified cancers based on type and related infections. For each of these cancer groups, we calculated crude incidence rates and evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported the associations using adjusted hazard ratios (aHR) over a grid of CD4 values for a reference value of 200 cells/µl, and by estimating the aHR per decrease of 100 CD4 cells/µl after assuming a linear relationship between the log hazard and CD4 cell counts. Results: We analysed 3,695,723 PLWH, of which 16,274 developed cancer, for an overall crude cancer incidence rate of 169 per 100,000 person-years (py). The most common cancers were cervical cancer (4,151 cases in women, rate of 59 per 100,000 py), Kaposi Sarcoma (2,311 cases, rate of 24 per 100,000 py), and non-Hodgkin lymphoma (1,101 cases, rate of 11 per 100,000 py). There were 6,482 PLWH diagnosed with cancer not related to infection (rate of 67 per 100,000 py). The association between low CD4 cell count and higher rates of cancer was strongest in conjunctival cancer (aHR per decrease of 100 CD4 cells/µl: 1.47, 95% confidence interval [CI] 1.39-1.55), followed by Kaposi Sarcoma (aHR 1.23, 95% CI 1.20-1.26) and non-Hodgkin lymphoma (aHR 1.16, 95% CI 1.12-1.19). Among the infection-unrelated cancers, we found low CD4 cell count to be associated with higher rates of squamous cell carcinoma of the skin (aHR 1.06, 95% CI 1.02-1.11) and cancer of the oesophagus (aHR 1.06, 95 CI 1.00-1.11). We found no association between CD4 cell count and both breast and prostate cancer incidence.Conclusions: Low time-updated 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 South Africa, a region heavily burdened by cancers attributable to infections.

Objective The objective of this study was to quantify the impact of the South African antiretroviral treatment programme on the age-standardised incidence rate of Kaposi sarcoma among black South African residents of all ages. Methods We performed an interrupted time series analysis using routinely collected, histologically confirmed surveillance data from the South African National Cancer Registry for the years 1999 to 2016. The analysis was performed using R statistical software. The total number of cases was 29,623 (12,475 females and 17,166 males). The background antiretroviral treatment coverage was less than 1% at the time that the antiretroviral programme was introduced and increased to over 50% in 2016. Results In 1999, the age-standardised rates were 1.48 and 2.82 cases per 100,000 per year for black females and males, respectively. These rates increased to 5.52 and 7.46 in 2008 before declining. The antiretroviral treatment programme was started in 2004. Five years after 2008 (nine years after the antiretroviral programme was introduced), the predicted standardised rates were 58.3% and 50.3% lower for females and males, respectively, than what they would have been without the treatment programme. Conclusion Introduction of the antiretroviral treatment programme was associated with a decrease of over 50% in the predicted age-standardised incidence rates of Kaposi sarcoma.

The Johannesburg Cancer Study (JCS) aims were to examine whether cancer risk factors identified in Western countries applied to black patients in Johannesburg, South Africa and to understand the impact of HIV on cancer risk, with a view to identifying previously unrecognised HIV associated cancers. A total of 24 971 black patients with an incident histologically proven (>95%) cancer of any type were enrolled between 1995-2016. Response rates were >90%. Patients provided informed consent, lifestyle and demographic information using a structured questionnaire; 19 351 provided a serum sample and 18 972 a whole blood sample for genomic analyses. This is currently the largest cancer epidemiological biobank in Africa. JCS uses a cancer case-control method; controls being cancer types unrelated to exposures of interest. Published results show the importance of HIV in several cancers known to be infection associated e.g. Kaposi sarcoma (OR = 1683; CI = 595-5194) in those with high Kaposi-sarcoma-associated-herpesvirus titres; no effect of HIV on lung or liver cancer-in the latter showing a strong association with HBVDNA, sAg and c positivity (OR = 47; CI = 21-104). Comparable data to higher-income country studies include lung cancer ORs in relation to smoking (15+g tobacco/day) (ORMales = 37; CI = 21-67, ORFemales = 18.5; CI = 8-45) and associations between alcohol and oesophageal cancer in smokers (ORM&F = 4.4; CI = 3-6). Relationship between hormonal contraception declined to null 10 or more years after stopping for breast (OR = 1.1; CI = 0.9-1.4) and cervical cancer (OR = 1.0;CI = 0.8-1.2), and protective effects shown, five or more years after stopping for ovarian (OR = 0.6; CI = 0.4-1) and endometrial cancer (OR = 0.4; CI = 0.2-0.9). Preferential access is based on data requests promoting data pooling, equal collaborative opportunities and enhancement of research capacity in South Africa. The JCS is a practical and valid design in otherwise logistically difficult settings.

People living with HIV or AIDS are at increased risk of Hodgkin and non-Hodgkin lymphoma compared with HIV-negative individuals. Data on the risk of multiple myeloma or leukaemia are inconsistent and of low quality but the risk does not seem to be increased. Specific haematological malignancies occur in different contexts of age, CD4 cell count, HIV control, viral co-infections, or chronic inflammation, and the expansion of combination antiretroviral therapy has led to varied demographic and epidemiological shifts among people with HIV. Increased use of combination antiretroviral therapy has substantially reduced the risks of diffuse large B-cell lymphoma, Burkitt lymphoma, and primary CNS lymphoma, and to a lesser extent, Hodgkin lymphoma. There is no effect of combination antiretroviral therapy use on multiple myeloma or leukaemia. Although many cases of HIV are in low-income and middle-income countries, high-quality epidemiological data for haematological malignancies from these regions are scarce. Closing this gap is an essential first step in decreasing mortality from HIV-associated haematological malignancies worldwide. Finally, although multicentric Castleman disease is not a neoplastic condition, it is an emerging precursor to neoplastic high-grade B-cell lymphoproliferation among people with HIV, especially for individuals on long-term combination antiretroviral therapy with well controlled HIV.