Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations.

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Thirteen cancers associated with HIV infection in a Black South African cancer patient population (1995-2016).

South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995-2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case-control associations between specific cancers and HIV, using participants with non-infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (ORadj ; 95%CI): (99.1;72.6-135.1), non-Hodgkin lymphoma (11.3;9.3-13.6), cervical cancer (2.7;2.4-3.0), Hodgkin lymphoma (3.1;2.4-4.2), cancer of the eye/conjunctiva (18.7;10.1-34.7), anogenital cancers (anus [2.1;1.4-3.2], penis [5.4;2.7-10.5], vulva [4.8;3.5-6.4], vagina [5.5;3.0-10.2]), oropharyngeal cancer (1.6;1.3-1.9), squamous cell carcinoma of the skin (3.5;2.4-4.9), melanoma (2.0;1.2-3.5) and cancer of the larynx (1.7;1.3-2.4). Kaposi's sarcoma odds ratios increased from the pre-ART (1995-2004) to the early ART (2005-2009) period but declined in the late ART (2010-2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV-associated cancers found in other African settings. The odds ratios of conjunctival and HPV-related cancers continue to rise in the ART era as the HIV positive population ages.

Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout.

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj ) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj  = 1.4 [95%CI 1.23-1.52]), in persons with HIV, (ORadj  = 4.2 [95%CI 3.74-4.73]) and lower in high school leavers (ORadj  = 0.7 [95%CI 0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend < .001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend < .001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend < .001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI 1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene.

Usefulness of high-risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta-analysis.

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.

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study.

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.

Colorectal cancer incidence and mortality trends by sex and population group in South Africa: 2002-2014.

BACKGROUND: South 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. METHODS: Incidence 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. RESULTS: A 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 < 0.001). For ASMR overall, there was 1.3% increase from 2002 to 2014 (95% CI: 0.1-2.6, p-value < 0.001). The ASIR and ASMR among population groups were stable, with the exception of the Black population group. The ASIR increased consistently at 4.3% for black males (95% CI: 1.9-6.7, p-value < 0.001) and 3.4% for black females (95% CI: 1.5-5.3, p-value < 0.001) from 2002 to 2014, respectively. Similarly, ASMR for black males and females increased by 4.2% (95% CI: 2.0-6.5, p-value < 0.001) and 3.4% (, 95%CI: 2.0-4.8, p-value < 0.01) from 2002 to 2014, respectively. CONCLUSIONS: The 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.

Cervical cancer survival in sub-Saharan Africa by age, stage at diagnosis and Human Development Index: A population-based registry study.

Cervical cancer is the leading cause of cancer death in African women. We sought to estimate population-based survival and evaluate excess hazards for mortality in African women with cervical cancer, examining the effects of country-level Human Development Index (HDI), age and stage at diagnosis. We selected a random sample of 2760 incident cervical cancer cases, diagnosed in 2005 to 2015 from 13 population-based cancer registries in 11 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2735 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival were estimated by registry, stage and country-level HDI. We used flexible Poisson regression models to estimate the excess hazards for death adjusting for age, stage and HDI. Among patients with known stage, 65.8% were diagnosed with Stage III-IV disease. The 5-year relative survival for Stage I-II cervical cancer in high HDI registry areas was 67.5% (42.1-83.6) while it was much lower (42.2% [30.6-53.2]) for low HDI registry areas. Independent predictors of mortality were Stage III-IV disease, medium to low country-level HDI and age >65 years at cervical cancer diagnosis. The average relative survival from cervix cancer in the 11 countries was 69.8%, 44.5% and 33.1% at 1, 3 and 5 years, respectively. Factors contributing to the HDI (such as education and a country's financial resources) are critical for cervical cancer control in SSA and there is need to strengthen health systems with timely and appropriate prevention and treatment programmes.

Association of genetic variants in CHEK2 with oesophageal squamous cell carcinoma in the South African Black population.

Oesophageal squamous cell carcinoma (OSCC) has a high incidence in southern Africa and a poor prognosis. Limited information is available on the contribution of genetic variants in susceptibility to OSCC in this region. However, recent genome-wide association studies have identified multiple susceptibility loci in Asian and European populations. In this study, we investigated genetic variants from seven OSCC risk loci identified in non-African populations for association with OSCC in the South African Black population. We performed association studies in a total of 1471 cases and 1791 controls from two study sample groups, which included 591 cases and 852 controls from the Western Cape and 880 cases and 939 controls from the Johannesburg region in the Gauteng province. Thereafter, we performed a meta-analysis for 11 variants which had been genotyped in both studies. A single nucleotide polymorphism in the CHEK2 gene, rs1033667, was significantly associated with OSCC [P = 0.002; odds ratio (OR) = 1.176; 95% confidence interval (CI): 1.06-1.30]. However, single nucleotide polymorphisms in the CASP8/ALS2CR12, TMEM173, PLCE1, ALDH2, ATP1B2/TP53 and RUNX1 loci were not associated with the disease (P > 0.05). The lack of association of six of these loci with OSCC in South African populations may reflect different genetic risk factors in non-African and African populations or differences in the genetic architecture of African genomes. The association at CHEK2, a gene with key roles in cell cycle regulation and DNA repair, in an African population provides further support for the contribution of common genetic variants at this locus to the risk of oesophageal cancer.

Knowledge, attitudes and practices of young people in Zimbabwe on cervical cancer and HPV, current screening methods and vaccination.

BACKGROUND: The rise in cervical cancer trends in the past two decades has coincided with the human immunodeficiency virus (HIV) epidemic especially in the sub-Saharan African region. Young people (15 to 24 years old) are associated with many risk factors such as multiple sexual partners, early sexual debut, and high HIV incidences, which increase the chances of developing cervical cancer. The National Cancer Prevention and Control Strategy for Zimbabwe (2014-2018) highlights that no cancer communication strategy focusing on risk factors as primary cancer prevention. Therefore, the study aims to determine the knowledge, attitude and practices of young people in Zimbabwe on cervical cancer, screening, human papillomavirus (HPV) and vaccination. METHODS: A cross-sectional survey assessing young people's knowledge, attitude and practices concerning cervical cancer was conducted in five provinces in Zimbabwe. A total of 751 young people were recruited through a three-stage cluster design from high schools and universities. Knowledge, attitudes and practices were assessed using questions based and adapted from the concepts of the Health Belief Model (HBM) and the Cervical Cancer Measuring tool kit-United Kingdom (UK). RESULTS: Most young people, 87.47% (656/750) claimed to know what the disease called cervical cancer is, with a mean score of 89.98% [95% CI 73.71.11-96.64] between high school and 86.72% [95% CI 83.48-89.40] among university students. There was no significant difference in mean scores between high school and university students (p = 0.676). A risk factor knowledge proficiency score of ≥13 out of 26 was achieved in only 13% of the high school respondents and 14% of the university respondents with a broad range of misconceptions about cervical cancer risk factors in both females and males. There was not much difference on comprehensive knowledge of cervical cancer and its risk factors between female and male students, with the difference in knowledge scores among high school (p = 0.900) and university (p = 0.324) students not statistically significant. In contrast, 43% of respondents heard of cervical cancer screening and prevention, and 47% knew about HPV transmission and prevention. Parents' educational level, province and smoking, were some of the factors associated with knowledge of and attitude towards cervical among high school and university students. CONCLUSION: This study revealed that young people in Zimbabwe have an idea about cervical cancer and the seriousness thereof, but they lack adequate knowledge of risk factors. Cervical cancer education and awareness emphasising causes, risk factors and care-seeking behaviours should be commissioned and strengthen at the community, provincial and national level. Developing a standard cervical cancer primary prevention tool that can be integrated into schools can be a step towards addressing health inequity.

Trends in Melanoma Mortality in the Population Groups of South Africa.

The incidence of cutaneous melanoma (CM) is increasing in countries around the world. However, little is known about melanoma trends in African countries by population group. We studied CM mortality in South Africa from 1997 to 2014 to partly address this knowledge gap. Unit record mortality data for all South Africans who died from CM (n = 8,537) were obtained from Statistics South Africa. Join-point regression models were used to assess whether there was a statistically significant change in the direction and/or magnitude of the annual trends in CM mortality. A significant increasing trend of 11% per year was observed in age-adjusted mortality rates in men between 2000 and 2005 (p < 0.01), rising from 2 to 3 per 100,000. There was also a statistically significant increase of 180% per year among White South Africans from 1997 to 1999 (p < 0.05) and of 3% from 1999 to 2014 (p < 0.01). These results may be used to inform CM awareness campaigns and will motivate efforts to improve the collection and analysis of relevant statistics regarding the present burden of CM in South Africa.

Temporal trends in the epidemiology of cervical cancer in South Africa (1994-2012).

Cervical cancer (CC) is the leading cause of cancer death among female South Africans (SA). Improved access to reproductive health services following multi-ethnic democracy in 1994, HIV epidemic, and the initiation of CC population-based screening in early 2000s have influenced the epidemiology of CC in SA. We therefore evaluated the trends in CC age-standardised incidence (ASIR) (1994-2009) and mortality rates (ASMR) (2004-2012) using data from the South African National Cancer Registry and the Statistics South Africa, respectively. Five-year relative survival rates and average per cent change (AAPC) stratified by ethnicity and age-groups was determined. The average annual CC cases and mortalities were 4,694 (75,099 cases/16 years) and 2,789 (25,101 deaths/9 years), respectively. The ASIR was 22.1/100,000 in 1994 and 23.3/100,000 in 2009, with an average annual decline in incidence of 0.9% per annum (AAPC = -0.9%, p-value < 0.001). The ASMR decreased slightly by 0.6% per annum from 13.9/100,000 in 2004 to 13.1/100,000 in 2012 (AAPC = -0.6%, p-value < 0.001). In 2012, ASMR was 5.8-fold higher in Blacks than in Whites. The 5-year survival rates were higher in Whites and Indians/Asians (60-80%) than in Blacks and Coloureds (40-50%). The incidence rate increased (AAPC range: 1.1-3.1%, p-value < 0.001) among young women (25-34 years) from 2000 to 2009. Despite interventions, there were minimal changes in overall epidemiology of CC in SA but there were increased CC rates among young women and ethnic disparities in CC burden. A review of the CC national policy and directed CC prevention and treatment are required to positively impact the burden of CC in SA.

Liver cancer mortality trends in South Africa: 1999-2015.

BACKGROUND: In South Africa (SA), liver cancer (LC) is a public health problem and information is limited. METHODS: Joinpoint regression analysis was computed for the most recent LC mortality data from Statistics South Africa (StatsSA), by age group, sex and population group. The mortality-to-incidence ratios (MIRs) were calculated as the age-adjusted mortality rate divided by the age-adjusted incidence rate. RESULTS: From 1999 to 2015, the overall LC mortality significantly decreased in men (- 4.9%) and women (- 2.7%). Overall a significant decrease was noted in black African men aged 20-29 and 40-49 years, and white women older than 60 years but mortality rates increased among 50-59 and 60-69 year old black African men (from 2010/2009-2015) and women (from 2004/2009-2015). The mortality rates increased with age, and were higher among blacks Africans compared to whites in all age groups - with a peak black African-to-white mortality rate ratio of six in men and three in women at ages 30-39 years. The average MIR for black African men and women was 4 and 3.3 respectively, and 2.2 and 1.8 in their white counterparts. Moreover, decreasing LC mortality rates among younger and the increase in rates in older black Africans suggest that the nadir of the disease may be near or may have passed. CONCLUSIONS: Findings of population-age subgroup variations in LC mortality and the number of underdiagnosed cases can inform surveillance efforts, while more extensive investigations of the aetiological risk factors are needed. IMPACT: There was a large race, sex and age differences in trends of LC mortality in SA. These findings should inform more extensive evaluation of the aetiology and risk factors of LC in the country in order to guide control efforts.

Establishment of a cancer surveillance programme: the South African experience.

Cancer is projected to become a leading cause of morbidity and mortality in low-income and middle-income countries in the future. However, cancer incidence in South Africa is largely under-reported because of a lack of nationwide cancer surveillance networks. We describe present cancer surveillance activities in South Africa, and use the International Agency for Research on Cancer framework to propose the development of four population-based cancer registries in South Africa. These registries will represent the ethnic and geographical diversity of the country. We also provide an update on a cancer surveillance pilot programme in the Ekurhuleni Metropolitan District, and the successes and challenges in the implementation of the IARC framework in a local context. We examine the development of a comprehensive cancer surveillance system in a middle-income country, which might serve to assist other countries in establishing population-based cancer registries in a resource-constrained environment.

Childhood cancer incidence patterns by race, sex and age for 2000-2006: a report from the South African National Cancer Registry.

Higher childhood cancer incidence rates are generally reported for high income countries although high quality information on descriptive patterns of childhood cancer incidence for low or middle income countries is limited, particularly in Sub-Saharan Africa. There is a need to quantify global differences by cancer types, and to investigate whether they reflect true incidence differences or can be attributed to under-diagnosis or under-reporting. For the first time, we describe childhood cancer data reported to the pathology report-based National Cancer Registry of South Africa in 2000-2006 and compare our results to incidence data from Germany, a high income country. The overall age-standardized incidence rate (ASR) for South Africa in 2000-2006 was 45.7 per million children. We observed substantial differences by cancer types within South Africa by racial group; ASRs tended to be 3-4-fold higher in South African Whites compared to Blacks. ASRs among both Black and White South Africans were generally lower than those from Germany with the greatest differences observed between the Black population in South Africa and Germany, although there was marked variation between cancer types. Age-specific rates were particularly low comparing South African Whites and Blacks with German infants. Overall, patterns across South African population groups and in comparison to Germans were similar for boys and girls. Genetic and environmental reasons may probably explain rather a small proportion of the observed differences. More research is needed to understand the extent to which under-ascertainment and under-diagnosis of childhood cancers drives differences in observed rates.

Cancer diagnostic service use in people living with HIV in South Africa: A cross-sectional study.

OBJECTIVE: The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people living with HIV (PLHIV) within South Africa (SA) using national laboratory database. DESIGN: We linked HIV and cancer laboratory data from 2004-2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis. SETTING: We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA. STUDY POPULATION: Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004-2014. PRIMARY AND SECONDARY OUTCOMES: We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer. RESULTS: The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33-48] years for the study population with most cancers in PLHIV diagnosed in females 70.9% [n = 46,313]. Of all the PLHIV and cancer, 25% (n = 16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n = 10,235) travelling to Gauteng. KZN had 46.6% (n = 4,107) of its PLHIV getting cancer diagnosis in Gauteng. Western Cape had 95% (n = 6,200) of PLHIV getting cancer diagnosis within the province. CONCLUSIONS: Our results showed health systems inequalities across provinces in SA with respect to cancer diagnosis. KZN for example had nearly half of the PLHIV getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PLHIV in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country.

Cancer diagnostic service use in people with HIV in South Africa: a cross-sectional study.

Objective: The objective of this study was to map place of cancer diagnosis in relation to Human Immunodeficiency Virus (HIV) care centre among people with HIV (PWH) within South Africa (SA) using national laboratory database. Design: We linked HIV and cancer laboratory data from 2004-2014 using supervised machine-learning algorithms. We performed a cross-sectional analysis comparing province where individuals accessed their HIV care versus where they had their cancer diagnosis. Setting: We used laboratory test records related to HIV diagnostics and care, such as CD4 cell counts and percentages, rapid tests, qualitative Polymerase Chain Reaction (PCR), antibody and antigen tests for HIV data that was documented as HIV positive and laboratory diagnosed cancer records from SA. Study population: Our study population consisted of HIV records from the National Health Laboratory Service (NHLS) that linked to cancer record at the National Cancer Registry (NCR) between 2004- 2014. Primary and secondary outcomes: We linked HIV records from NHLS to cancer records at NCR in order to study the inherent characteristics of the population with both HIV and cancer. Results: The study population was 68,284 individuals with cancer and documented HIV related laboratory test. The median age at cancer diagnosis was 40 [IQR, 33-48] years for the study population with most cancers in PWH diagnosed in females 70.9% [n=46,313]. Of all the PWH and cancer, 25% (n=16,364 p < 0.001) sought treatment outside their province of residence with 60.7% (n=10,235) travelling to Gauteng. KZN had 46.6% (n=4,107) of its PWH getting cancer diagnosis in Gauteng. Western Cape had 95% (n=6,200) of PWH getting cancer diagnosis within the province. Conclusions: Our results showed health systems inequalities across provinces in South Africa with respect to cancer diagnosis. KZN for example had nearly half of the PWH getting cancer diagnosis outside the province while Western Cape is able to offer cancer diagnostic services to most of the PWH in the province. Gauteng is getting over burdened with referral for cancer diagnosis from other provinces. More effort is required to ensure equitable access to cancer diagnostic services within the country.

Biochemical progression free and overall survival among Black men with stage IV prostate cancer in South Africa: Results from a prospective cohort study.

BACKGROUND: Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first-line treatment for stage IV PCa. OBJECTIVE: To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. DESIGN, SETTING, AND PARTICIPANTS: Men diagnosed with prostate cancer (3/22/2016-10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate-specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. OUTCOMES MEASURES AND STATISTICAL ANALYSIS: We used Kaplan-Meier statistics to estimate OS and Cox regression models to identify predictors of OS. RESULTS AND LIMITATIONS: Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64-73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%-noncalculable), while biochemical progression-free survival was 2.36 years (95% CI: 2.03%-3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%-6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%-7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%-5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%-6.56%) were associated with worse OS. CONCLUSIONS: In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. PATIENT SUMMARY: In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.

The Incidence of Retinoblastoma in South Africa: Findings from the South African National Cancer Registry (2004-2018).

PURPOSE: To determine the frequency and incidence rate of retinoblastoma in children in South Africa from 2004 to 2018. METHODS: Incident cases of histologically diagnosed retinoblastoma were identified from the South African National Cancer Registry. Crude incidence rates were calculated using national population data on children <15 years and live births. Incidence rates were stratified and compared by age, sex and population group. Direct age-standardised incidence rates and comparative incidence ratios were calculated. RESULTS: The overall age-standardised incidence rate for children <15 years was 3.3 per million or 1 per 21 641 live births. Age-specific rates for children aged 0-4, 5-9 and 10-14 years were 7.7, 0.8 and 0.2 per million, respectively. There was no difference in incidence rates by sex. White children had a significantly higher incidence rate compared to other population groups, but this finding may be due to systemic biases introduced by access to healthcare in South Africa or study methodology. CONCLUSION: This is the largest study to provide population-based, histologically confirmed national estimates of retinoblastoma incidence from an African nation to date and affirms the need for high-quality cancer registries across the African continent.

Skin cancer risk factors among Black South Africans-The Johannesburg Cancer Study, 1995-2016.

BACKGROUND: The Black population has lower skin cancer incidence compared to White, Indian/Asian, and Mixed-race populations in South Africa; however, skin cancer still exists in the Black population. The aim of this study is to identify risk factors associated with skin cancer among Black South Africans. MATERIALS AND METHODS: A case-control study was conducted. Cases were patients with keratinocyte cancers (KCs) and/or melanoma skin cancers (MSCs) and controls were cardiovascular patients. Sociodemographic exposures, environmental health variables, smoking, and HIV status were assessed. Stepwise logistic regression was used to identify risk factors associated with KCs and MSCs. RESULTS: The KCs histological subtypes showed that there were more squamous cell carcinomas (SCCs) (78/160 in females, and 72/160 in males) than basal cell carcinomas (BCCs). The SCC lesions were mostly found on the skin of the head and neck in males (51%, 38/72) and on the trunk in females (46%, 36/78). MSC was shown to affect the skin of the lower limbs in both males (68%, 27/40) and females (59%, 36/61). Using females as a reference group, when age, current place of residency, type of cooking fuel used, smoking, and HIV status were adjusted for, males had an odds ratio (OR) of 2.04 for developing KCs (confidence interval [CI]: 1.08-3.84, p = .028). Similarly, when age, current place of residency, and place of cooking (indoors or outdoors) were adjusted for, males had an OR of 2.26 for developing MSC (CI: 1.19-4.29, p = .012). CONCLUSIONS: Differences in the anatomical distribution of KCs by sex suggest different risk factors between sexes. There is a positive association between being male, smoking, rural dwelling, and a positive HIV status with KCs and being male and rural dwelling with MSC. The rural dwelling was a newly found association with skin cancer and warrants further investigation.

Rule-Based Information Extraction from Free-Text Pathology Reports Reveals Trends in South African Female Breast Cancer Molecular Subtypes and Ki67 Expression.

Clinical information on molecular subtypes and the Ki67 index is critical for breast cancer (BC) prognosis and personalised treatment plan. Extracting such information into structured data is essential for research, auditing, and cancer incidence reporting and underpins the potential for automated decision support. Herewith, we developed a rule-based natural language processing algorithm that retrieved and extracted important BC parameters from free-text pathology reports towards exploring molecular subtypes and Ki67-proliferation trends. We considered malignant BC pathology reports with different free-text narrative attributes from the South African National Health Laboratory Service. The reports were preprocessed and parsed through the algorithm. Parameters extracted by the algorithm were validated against manually extracted parameters. For all parameters extracted, we obtained accurate annotations of 83-100%, 93-100%, 91-100%, and 92-100% precision, recall, F 1-score, and kappa, respectively. There was a significant trend in the proportion of each molecular subtype by patient age, histologic type, grade, Ki67, and race. The findings also showed significant association in the Ki67 trend with hormone receptors, human epidermal growth factors, age, grade, and race. Our approach bridges the gap between data availability and actionable knowledge and provides a framework that could be adapted and reused in other cancers and beyond cancer studies. Information extracted from these reports showed interesting trends that may be exploited for BC screening and treatment resources in South Africa. Finally, this study strongly encourages the implementation of a synoptic style pathology report in South Africa.