Chantal Babb

Dominant genetic aberrations and coexistent EBV infection in HIV-related oral plasmablastic lymphomas

We present common cytogenetic features in the largest cohort of plasmablastic lymphoma (PBL) of the oral cavity published to date. This cohort included 45 patients, 32 of whom had a known HIV status, of which 31 were HIV positive. Ninety eight per cent of all PBL cases were known to be EBV positive. In line with previous studies, we found that rearrangements of the MYC gene was the most common genetic abnormality seen in 60% of cases with the immunoglobulin heavy chain (IGH) locus as a partner in 51% of cases. Additional complex genetic aberrations were frequent, in particular, an increased copy number of the CCND1 gene was seen in 41% of cases with true amplification of CCND1 in 15% of cases. Aneuploidy was also observed for the BCL6 gene in 28% of cases. Interestingly, rearrangements of both IGH genes were detected in 16% of cases with t(14;18) and t(11;14) respectively involved in conjunction with a t(8;14) in two cases. These bi-allelic IGH rearrangements have not been described before in oral PBL. Our results reinforce the notion that EBV infection and MYC rearrangements are important events in the pathogenesis of oral PBL. The genetic diversity and complexity observed in these cases, underlines the importance to genetically characterise PBL patients at presentation as this may inform the choice of more effective treatment modalities.

Mucosal Alpha-Papillomaviruses are not associated with Esophageal Squamous Cell Carcinomas: Lack of Mechanistic Evidence from South Africa, China and Iran and from a World-Wide Meta-Analysis.

Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol‐ and formalin‐fixed paraffin‐embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high‐incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha‐papillomaviruses by two sensitive, broad‐spectrum genotyping methods, and for the markers of HPV‐transformed phenotype: (i) HPV16/18 viral loads by quantitative real‐time PCR, (ii) type‐specific viral mRNA by E6*I/E6 full‐length RT‐PCR assays and (iii) expression of cellular protein p16INK4a. Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16INK4a negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16INK4a upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16INK4a upregulation. These results were supported by a meta‐analysis of 14 other similar studies regarding HPV‐transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.

South African National Cancer Registry: Effect of withheld data from private health systems on cancer incidence estimates

BACKGROUNDnThe National Cancer Registry (NCR) was established as a pathology-based cancer reporting system. From 2005 to 2007, private health laboratories withheld cancer reports owing to concerns regarding voluntary sharing of patient data.nnnOBJECTIVESnTo estimate the impact of under-reported cancer data from private health laboratories.nnnMETHODSnA linear regression analysis was conducted to project expected cancer cases for 2005-2007. Differences between actual and projected figures were calculated to estimate percentage under-reporting.nnnRESULTSnThe projected NCR case total varied from 53,407 (3.8% net increase from actual cases reported) in 2005 to 54,823 (3.7% net increase) in 2007. The projected number of reported cases from private laboratories in 2005 was 26,359 (19.7% net increase from actual cases reported), 27,012 (18.8% net increase) in 2006 and 27,666 (28.4% net increase) in 2007.nnnCONCLUSIONnWhile private healthcare reporting decreased by 28% from 2005 to 2007, this represented a minimal impact on overall cancer reporting (net decrease of <4%).

Erratum to “Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009)”

Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986–2006) and data on mortality (1997–2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

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.

Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

Little is known about the incidence patterns of hematologic malignancies in Sub‐Saharan Africa, including South Africa. We estimated incidence rates of pathology‐confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non‐Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender‐specific age‐standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20–50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set‐up of the NCR (pathology‐based) could lead to some degree of under‐ascertainment in all groups. This is the first country‐wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer‐related health care.

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

BackgroundHIV 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.MethodsThe 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.ResultsA 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.ConclusionsIn 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.

The South African National Cancer Registry: an update

We would like to take this opportunity to correct the misconception created by the News piece published in The Lancet Oncology regarding the “demise” of the South African National Cancer Registry (NCR). The NCR, a division of the National Health Laboratory Service, is the primary cancer surveillance system and largest repository of cancer data in South Africa. It was established in 1986 as a voluntary, pathologybased cancer surveillance system, and continues to operate; its database contains over 1·2 million cancer records with about 80 000 new cases added each year. The misconception about the NCR referred to above might have come about because the NCR has had diffi culties in the past due to changes in leadership, high staff turnover, and a lack of political and fi nancial prioritisation of cancer surveillance caused by competing national health priorities at the peak of the HIV epidemic. As a result of severe resource constraints, the NCR continued to obtain data but was unable to regularly produce reports. Additionally, between 2004 and 2010, some private laboratories withheld data because of concerns about voluntarily submitting confi dential patient information to the registry without the protection of government legislation. However, in 2011, Regulation 380 of the National Health Act (Act 61 of 2003) formally established the NCR as South Africa’s main cancer surveillance agency; the legislation makes reporting all confi rmed cancer diagnoses to the registry obligatory. Additionally, the Regulation mandated the NCR to implement population-based cancer registration in South Africa. With renewed political support, NCR has been revitalised. To expedite data processing, the registry has moved to electronic reporting of pathology data from laboratories. Cancer incidence reports for 2000–07 have been published online with further reports in progress. After great eff ort from NCR staff , we aim to soon report cancers within timeframes similar to those of leading international cancer registries. The NCR has developed a 10-year business plan for the implementation of both new population-based and existing pathology-based registration for the country. Fundraising activities have started, and a pilot populationbased registry is operational in one district of the country (Ekurhuleni District, Gauteng), with more to follow. In view of the concern among stakeholders about the decline in reporting from private laboratories in the past, our researchers did a thorough investigation to quantify the eff ect of withheld reports on national cancer surveillance. We found a marginal eff ect on overall reporting; NCR will submit these fi ndings for peer-reviewed publication soon. The NCR remains the main source of cancer data for South Africa, with laboratory-based reporting yielding high specifi city. With the imminent implementation of national health insurance, it is vital for the country to be able to quantify the burden of cancer for national resource planning. Increased investment in the NCR will assist the organisation to improve South African cancer surveillance.

The South African paediatric tumour registry - 25 years of activity

The South African Childrens Tumour Registry was established 25 years ago as it was essential to collect data on malignant disease in the paediatric population that can be used for statistical research in an efficient and sustainable way. The Registry is a useful and significant repository of specific paediatric data, along with the recently revitalised National Cancer Registry, to serve the needs of the cancer research community.We appreciate Drs Stefan and Stones highlighting the value of cancer registries. Establishing a comprehensive population-based cancer registry in South Africa is most important and long overdue. This does not preclude specialised registries, provided that all cancers are reported to the main, statutory registry. Best practice is inclusive reporting of all cancers to a single registry for all age groups, which enables national trends to be described for the entire South African population, including rural areas.