Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

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.

Cervical cancer risk and impact of Pap-based screening in HIV-positive women on antiretroviral therapy in Johannesburg, South Africa.

Data on invasive cervical cancer (ICC) incidence in HIV-positive women and the effect of cervical cancer screening in sub-Saharan Africa are scarce. We estimated i) ICC incidence rates in women (≥18 years) who initiated antiretroviral therapy (ART) at the Themba Lethu Clinic (TLC) in Johannesburg, South Africa, between 2004 and 2011 and ii) the effect of a Pap-based screening program. We included 10,640 women; median age at ART initiation: 35 years [interquartile range (IQR) 30-42], median CD4 count at ART initiation: 113 cells/µL (IQR 46-184). During 27,257 person-years (pys), 138 women were diagnosed with ICC; overall incidence rate: 506/100,000 pys [95% confidence interval (CI) 428-598]. The ICC incidence rate was highest (615/100,000 pys) in women who initiated ART before cervical cancer screening became available in 04/2005 and was lowest (260/100,000 pys) in women who initiated ART from 01/2009 onward when the cervical cancer screening program and access to treatment of cervical lesions was expanded [adjusted hazard ratio (aHR) 0.42, 95% CI 0.20-0.87]. Advanced HIV/AIDS stage (4 versus 1, aHR 1.95, 95% CI 1.17-3.24) and middle age at ART initiation (36-45 versus 18-25 years, aHR 2.51, 95% CI 1.07-5.88) were risk factors for ICC. The ICC incidence rate substantially decreased with the implementation of a Pap-based screening program and improved access to treatment of cervical lesions. However, the risk of developing ICC after ART initiation remained high. To inform and improve ICC prevention and care for HIV-positive women in sub-Saharan Africa, implementation and monitoring of cervical cancer screening programs are essential.

Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) per 100,000 person-years after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment.

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.

HIV testing and burden of HIV infection in black cancer patients in Johannesburg, South Africa: a cross-sectional study.

BACKGROUND: HIV infection is a known risk factor for cancer but little is known about HIV testing patterns and the burden of HIV infection in cancer patients. We did a cross-sectional analysis to identify predictors of prior HIV testing and to quantify the burden of HIV in black cancer patients in Johannesburg, South Africa. METHODS: The Johannesburg Cancer Case-control Study (JCCCS) recruits newly-diagnosed black cancer patients attending public referral hospitals for oncology and radiation therapy in Johannesburg . All adult cancer patients enrolled into the JCCCS from November 2004 to December 2009 and interviewed on previous HIV testing were included in the analysis. Patients were independently tested for HIV-1 using a single ELISA test . The prevalence of prior HIV testing, of HIV infection and of undiagnosed HIV infection was calculated. Multivariate logistic regression models were fitted to identify factors associated with prior HIV testing. RESULTS: A total of 5436 cancer patients were tested for HIV of whom 1833[33.7% (95% CI=32.5-35.0)] were HIV-positive. Three-quarters of patients (4092 patients) had ever been tested for HIV. The total prevalence of undiagnosed HIV infection was 11.5% (10.7-12.4) with 34% (32.0-36.3) of the 1833 patients who tested HIV-positive unaware of their infection. Men >49 years [OR 0.49(0.39-0.63)] and those residing in rural areas [OR 0.61(0.39-0.97)] were less likely to have been previously tested for HIV. Men with at least a secondary education [OR 1.79(1.11-2.90)] and those interviewed in recent years [OR 4.13(2.62 - 6.52)] were likely to have prior testing. Women >49 years [OR 0.33(0.27-0.41)] were less likely to have been previously tested for HIV. In women, having children <5 years [OR 2.59(2.04-3.29)], hormonal contraceptive use [OR 1.33(1.09-1.62)], having at least a secondary education [OR:2.08(1.45-2.97)] and recent year of interview [OR 6.04(4.45-8.2)] were independently associated with previous HIV testing. CONCLUSIONS: In a study of newly diagnosed black cancer patients in Johannesburg, over a third of HIV-positive patients were unaware of their HIV status. In South Africa black cancer patients should be targeted for opt-out HIV testing.

Kaposi's Sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era.

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/µL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

Patterns and trends of HPV-related cancers other than cervix in South Africa from 1994-2013.

BACKGROUND: HPV infection causes several cancers which include cervical, vaginal, vulval, penile and oropharyngeal cancer (OPC). Understanding the burden of HPV-related cancers is important for guiding cancer prevention and treatment interventions. METHODS: To inform policy, we analysed trends of age-standardised incidence (ASIR) and mortality (ASMR) rates for HPV-related head and neck (HNC) and anogenital cancers (AGC) in South Africa between 1994 and 2013. RESULTS: A total of 1 028 330 incident cancers and 617 044 cancer-related deaths were reported during the study period. The overall ASIR (-5.5%) and ASMR (-2.2%) for HNC declined, in part related to the anti-smoking legislation. In contrast, incidence (2.9%) and mortality (0.8%) rates for AGC increased with the rising HIV prevalence. ASIR for oral cavity cancer (OCC: -6.3%) and laryngeal cancer (LC: -11.3%) declined, including mortality associated with these cancers (OCC:-1.9%, and LC:-2.6%). However, oropharyngeal cancer showed a slower rate of decline in ASIR (-4.4%) and ASMR did not change. Compared to women, ASIR and ASMR for HNC were 3-fold higher among men. ASIR for both anal (7.5%) and vulval cancer (16.1%) increased. Median age at diagnosis of vulval cancer declined by 18 years (p-value = 0.01). Mortality rates for anal (3.9%) and vulval (2.6%) cancer increased. ASIR (-3.2%) and ASMR (-2.0%) for penile cancer declined. Rates for vaginal cancer did not change. CONCLUSIONS: Anal and vulval cancers have increased over the reporting period. There is need to continuously monitor trends of these cancers. Implementation of HPV vaccination could significantly reduce the burden of HPV-related cancers.

The burden of cancers associated with HIV in the South African public health sector, 2004-2014: a record linkage study.

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

Cancer in adolescents and young adults living with HIV.

PURPOSE OF REVIEW: Adults living with HIV have an increased risk of malignancy yet there is little data for adolescents and young adults. We reviewed recently published cancer epidemiology, treatment, and outcome data for adolescents and young adults living with HIV (AYALHIV) aged 10 to less than 25 years between 2016 and 2017. RECENT FINDINGS: AYALHIV are at increased risk of developing cancer compared to their uninfected peers. Kaposi sarcoma and non-Hodgkin lymphoma occur most frequently with variation by geographical region. Increased cancer risk is associated with HIV-related immunosuppression and coinfection with oncogenic viruses. Published data, particularly on posttreatment outcomes, remain limited and analyses are hampered by lack of data disaggregation by age and route of HIV transmission. SUMMARY: Although data are sparse, the increased cancer risk for AYALHIV is the cause for concern and must be modified by improving global access and uptake of antiretroviral therapy, human papilloma virus (HPV) and hepatitis B virus (HBV) vaccination, screening for hepatitis B and C infection, and optimized cancer screening programs. Education aimed at reducing traditional modifiable cancer risk factors should be embedded within multidisciplinary services for AYALHIV.

Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa.

BACKGROUND: Ninety percent of the world's 2.1 million HIV-infected children live in sub-Saharan Africa, and 2.5% of South African children live with HIV. As HIV care and treatment programmes are scaled-up, a rise in loss to follow-up (LTFU) has been observed. OBJECTIVE: The aim of the study was to determine the rate of LTFU in children receiving antiretroviral treatment (ART) and to identify baseline characteristics associated with LTFU in the first year of treatment. We also explored the effect of patient characteristics at 12 months treatment on LTFU in the second year. METHODS: The study is an analysis of prospectively collected routine data of HIV-infected children at the Harriet Shezi Children's Clinic (HSCC) in Soweto, Johannesburg. Cox proportional hazards models were fitted to investigate associations between baseline characteristics and 12-month characteristics with LTFU in the first and second year on ART, respectively. RESULTS: The cumulative probability of LTFU at 12 months was 7.3% (95% CI 7.1-8.8). In the first 12 months on ART, independent predictors of LTFU were age <1 year at initiation, recent year of ART start, mother as a primary caregiver, and being underweight (WAZ ≤ -2). Among children still on treatment at 1 year from ART initiation, characteristics that predicted LTFU within the second year were recent year of ART start, mother as a primary caregiver, being underweight (WAZ ≤ -2), and low CD4 cell percentage. CONCLUSIONS: There are similarities between the known predictors of death and the predictors of LTFU in the first and second years of ART. Knowing the vital status of children is important to determine LTFU. Although HIV-positive children cared for by their mothers appear to be at greater risk of becoming LTFU, further research is needed to explore the challenges faced by mothers and other caregivers and their impact on long-term HIV care. There is also a need to investigate the effects of differential access to ART between mothers and children and its impact on ART outcomes in children.