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.

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.

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.

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.

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.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

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.

Epidemiology of Kaposi's sarcoma in sub-Saharan Africa.

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.

Cohort profile: the South African HIV Cancer Match (SAM) Study, a national population-based cohort.

PURPOSE: 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. PARTICIPANTS: PLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS. FINDINGS TO DATE: 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. FUTURE PLANS: 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.

Lifestyle factors associated with sex differences in Kaposi sarcoma incidence among adult black South Africans: A case-control study.

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.

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.

HPV types 16/18 L1 E6 and E7 proteins seropositivity and cervical cancer risk in HIV-positive and HIV-negative black South African women.

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.

Cervical cancer in women living in South Africa: a record linkage study of the National Health Laboratory Service and the National Cancer Registry.

INTRODUCTION: In countries with high HIV prevalence, it is important to understand the cervical cancer (CC) patterns by HIV status to ensure targeted prevention measures. We aimed to determine the factors associated with CC compared to non-infection related cancer in women living in South Africa. METHODS: This was a cross-sectional study of women aged 15 years and older diagnosed with CC and non-infection related cancer in the South African public health sector from 2004 to 2014. The National Cancer Registry provided data on cancer, whilst HIV status was determined from routinely collected HIV related data from the National Health Laboratory Service. We explored the association of HIV infection, age, ethnicity and calendar period with CC compared to non-infection related cancer. RESULTS: From 2004 to 2014, 49,599 women were diagnosed with CC, whilst 78,687 women had non-infection related cancer. About 40% (n = 20,063) of those with CC and 28% (n = 5,667) of those with non-infection related cancer had a known HIV status. The median age at CC diagnosis was 44 years (interquartile range (IQR): 37-52) and 54 years (IQR: 46-64) for HIV positive and negative women, respectively, and for non-infection related cancer, 45 years (IQR: 47-55) and 56 years (IQR: 47-66) for HIV negative and positive women, respectively. Diagnosis of CC was associated with HIV positivity, Black ethnicity, earlier calendar period (2004-2006) and the ages 30-49 years. In comparison with Black women, the odds of CC were 44% less in Coloured women, 50% less in Asian women and 51% less in White women. CONCLUSIONS: HIV positive women presented a decade earlier with CC compared to HIV negative women. A large proportion of women with CC were unaware of their HIV status with a disproportionate burden of CC in Black women. We recommend women attending CC screening facilities to be offered HIV testing so that recommendations for their follow-up visits are given according to their HIV status.

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.

Ranking lifestyle risk factors for cervical cancer among Black women: A case-control study from Johannesburg, South Africa.

BACKGROUND: Aside from human papillomavirus (HPV), the role of other risk factors in cervical cancer such as age, education, parity, sexual partners, smoking and human immunodeficiency virus (HIV) have been described but never ranked in order of priority. We evaluated the contribution of several known lifestyle co-risk factors for cervical cancer among black South African women. METHODS: We used participant data from the Johannesburg Cancer Study, a case-control study of women recruited mainly at Charlotte Maxeke Johannesburg Academic Hospital between 1995 and 2016. A total of 3,450 women in the study had invasive cervical cancers, 95% of which were squamous cell carcinoma. Controls were 5,709 women with cancers unrelated to exposures of interest. Unconditional logistic regression models were used to calculate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). We ranked these risk factors by their population attributable fractions (PAF), which take the local prevalence of exposure among the cases and risk into account. RESULTS: Cervical cancer in decreasing order of priority was associated with (1) being HIV positive (ORadj = 2.83, 95% CI = 2.53-3.14, PAF = 17.6%), (2) lower educational attainment (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 16.2%), (3) higher parity (3+ children vs 2-1 children (ORadj = 1.25, 95% CI = 1.07-1.46, PAF = 12.6%), (4) hormonal contraceptive use (ORadj = 1.48, 95% CI = 1.24-1.77, PAF = 8.9%), (5) heavy alcohol consumption (ORadj = 1.44, 95% CI = 1.15-1.81, PAF = 5.6%), (6) current smoking (ORadj = 1.64, 95% CI = 1.41-1.91, PAF = 5.1%), and (7) rural residence (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 4.4%). CONCLUNSION: This rank order of risks could be used to target educational messaging and appropriate interventions for cervical cancer prevention in South African women.

Corrigendum: Predicting Colorectal Cancer Recurrence and Patient Survival Using Supervised Machine Learning Approach: A South African Population-Based Study.

[This corrects the article DOI: 10.3389/fpubh.2021.694306.].

Use of Machine Learning and Statistical Algorithms to Predict Hospital Length of Stay Following Colorectal Cancer Resection: A South African Pilot Study.

The aim of this pilot study was to develop logistic regression (LR) and support vector machine (SVM) models that differentiate low from high risk for prolonged hospital length of stay (LOS) in a South African cohort of 383 colorectal cancer patients who underwent surgical resection with curative intent. Additionally, the impact of 10-fold cross-validation (CV), Monte Carlo CV, and bootstrap internal validation methods on the performance of the two models was evaluated. The median LOS was 9 days, and prolonged LOS was defined as greater than 9 days post-operation. Preoperative factors associated with prolonged LOS were a prior history of hypertension and an Eastern Cooperative Oncology Group score between 2 and 4. Postoperative factors related to prolonged LOS were the need for a stoma as part of the surgical procedure and the development of post-surgical complications. The risk of prolonged LOS was higher in male patients and in any patient with lower preoperative hemoglobin. The highest area under the receiving operating characteristics (AU-ROC) was achieved using LR of 0.823 (CI = 0.798-0.849) and SVM of 0.821 (CI = 0.776-0.825), with each model using the Monte Carlo CV method for internal validation. However, bootstrapping resulted in models with slightly lower variability. We found no significant difference between the models across the three internal validation methods. The LR and SVM algorithms used in this study required incorporating important features for optimal hospital LOS predictions. The factors identified in this study, especially postoperative complications, can be employed as a simple and quick test clinicians may flag a patient at risk of prolonged LOS.

Cancer in HIV-positive and HIV-negative adolescents and young adults in South Africa: a cross-sectional study.

OBJECTIVE: To determine the spectrum of cancers in adolescents and young adults (AYAs) living with and without HIV in South Africa. DESIGN: Cross-sectional study with cancer records provided by the National Cancer Registry (NCR) and HIV records from the National Health Laboratory Service (NHLS). SETTING AND PARTICIPANTS: The NHLS is the largest provider of pathology services in the South African public sector. 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=8479). HIV status was obtained through record linkages and text mining. PRIMARY AND SECONDARY OUTCOMES: We determined the spectrum of cancers by HIV status in AYAs. We used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex, ethnicity and calendar period. We imputed (post hoc) the HIV status for AYA with unknown HIV status. RESULTS: 8479 AYAs were diagnosed with cancer, HIV status was known for 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 OR (aOR) 218, 95% CI 89.9 to 530), cervical cancer (aOR 2.18, 95% CI 1.23 to 3.89), non-Hodgkin's lymphoma (aOR 2.12, 95% CI 1.69 to 2.66) and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27 to 5.86) than AYAs without HIV. About 44% (n=1062) of AYAs with HIV-related cancers had not been tested for HIV. CONCLUSIONS: Targeted HIV testing for AYAs diagnosed with cancer, followed by immediate start of antiretroviral therapy, screening for cervical precancer and vaccination against human papilloma virus is needed to decrease cancer burden in AYAs living with HIV in South Africa.

Cancer risk in adolescents and young adults living with HIV in South Africa: a nationwide cohort study.

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.