Moosa Patel

The spectrum of HIV‐1 related cancers in South Africa

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposis sarcoma (OR=21.9, 95% CI=12.5–38.6), non‐Hodgkin lymphoma (OR=5.0, 95%CI=2.7–9.5), vulval cancer (OR=4.8, 95%CI=1.9–12.2) and cervical cancer (OR=1.6, 95%CI=1.1–2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposis sarcoma, non‐Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposis sarcoma and non‐Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West. Int. J. Cancer 88:489–492, 2000.

The spectrum of human immunodeficiency virus-associated cancers in a South African black population: results from a case-control study, 1995-2004

The effect of the evolving HIV epidemic on cancer has been sparsely documented in Africa. We report results on the risk of cancer associated with HIV‐1 infection using data from an ongoing study. A case–control analysis was used to estimate the relative risk (odds ratio, OR) of cancer types known to be AIDS defining: Kaposis sarcoma (n = 333), non‐Hodgkin lymphoma (NHL, n = 223) and cancers of the cervix (n = 1,586), and 11 cancer types possibly associated with HIV infection: Hodgkin lymphoma (n = 154), cancers of other anogenital organs (n = 157), squamous cell cancer of the skin (SCC, n = 70), oral cavity and pharynx (n = 319), liver (n = 83), stomach (n = 142), leukemia (n = 323), melanoma (n = 53), sarcomas other than Kaposis (n = 93), myeloma (n = 189) and lung cancer (n = 363). The comparison group comprised 3,717 subjects with all other cancer types and 682 subjects with vascular disease. ORs were adjusted for age, sex (except cervical cancer), year of diagnosis, education and number of sexual partners. Significantly increased risks associated with HIV‐1 infection were found for HIV/AIDS associated Kaposis sarcoma (OR = 47.1, 95% CI = 31.9–69.8), NHL (OR = 5.9, 95% CI = 4.3–8.1) and cancer of the cervix (OR = 1.6, 95% CI = 1.3–2.0); Hodgkins disease (OR = 1.6, 95% CI = 1.0–2.7), cancers of anogenital organs other than the cervix (OR = 2.2; 95% CI = 1.4–3.3) and SCC (OR = 2.6, 95% CI = 1.4–4.9) were also significantly increased. No significant associations were found between HIV and any of the other cancers examined. Risks for HIV‐related cancers are consistent with previous studies in Africa, and are lower when compared to those observed in developed countries.

Risk factors for oesophageal, lung, oral and laryngeal cancers in black South Africans.

The authors used data collected from 1995 to 1999, from an on-going cancer case–control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5–4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6–204.6) for lung cancer in women, and 23.9 (95% CI 9.5–60.3) for lung cancer and 23.6 (95% CI 4.6–121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7–46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1–7.5) in men working in ‘potentially noxious’ industries. ‘Frequent’ alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0–2.9, for women and odds ratio=1.8, 95% CI 1.2–2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8–7.9 in males and odds ratio=4.8, 95% CI 3.2–6.1 in females). The above results are broadly in line with international findings.

Human Immunodeficiency Virus Infection and Hodgkin's Lymphoma in South Africa: An Emerging Problem

Hodgkins lymphoma (HL) occurs with increasing frequency in human-immunodeficiency-virus-(HIV-) infected individuals. The natural history and behaviour of HIV-HL is different, being more atypical and aggressive. The association between HIV and HL appears to be primarily EBV driven. HAART use does not significantly impact on the incidence of HL. Indeed, the risk of HL has increased in the post-HAART era. However, the advent of HAART has brought renewed hope, allowing standard therapeutic options to be used more optimally, with better treatment outcomes. Despite the renewed optimism, the overall survival of HIV-HL patients remains less favourable than that in HIV-seronegative patients. This is particularly true in sub-Saharan Africa, where there is a significant burden of HIV/AIDS and where more than half the patients are HAART naive at diagnosis of HL. The similarities and differences of a South African cohort of HIV-HL are presented in this paper.

Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

BackgroundInfection with human herpesvirus 8 (HHV-8), also known as Kaposis sarcoma-associated herpesvirus (KSHV), is the necessary causal agent in the development of Kaposis sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS.MethodsBetween January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis.ResultsOf the 2191 HIV-1 negative patients who did not have Kaposis sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis.ConclusionsAmong HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti-HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti-HHV-8 titers requires further, prospective study.

A Prospective Randomized Study of Chop Versus Chop Plus Alpha-2B Interferon in Patients with Intermediate and High Grade Non-Hodgkin's Lymphoma: The International Oncology Study Group NHL1 Study

The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. Background: The CHOP (Cyclophosphamide, Adriamycin, Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkins lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. Patients and Methods: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF SC for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week sub-cutaneously for 52 weeks in those patients who responded to CHOP plus INF. Results: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. Conclusions: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Classical Hodgkin Lymphoma involving the central nervous system (brain) - an unusual presentation.

Intracranial Hodgkin lymphoma (HL) is considered so atypical that an intracranial space‐occupying lesion in a patient with known HL should be thoroughly investigated to rule out a second disease process.

Human immunodeficiency virus infection and chronic myeloid leukemia

CML (chronic myeloid leukaemia) in association with HIV (human immunodeficiency virus) infection (HIV-CML) is rarely described and is likely to be coincidental. The natural history and behaviour of HIV-CML is different, being more atypical and aggressive. Both conditions, and their respective treatments may cause myelosuppression. Concurrent treatment with cART (combination antiretroviral therapy) and the tyrosine kinase inhibitors (TKIs) can result in appropriate control of CML and HIV infection, as well as long term survival. However, drug interactions between ARVs and TKIs may require adjustment of treatment.

Hepatosplenic T-cell lymphoma: A case series

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of Non-Hodgkin Lymphoma (NHL), grouped under the mature or peripheral T-cell lymphomas. It is characterised by extranodal infiltration and proliferation of malignant T-cells within the sinusoids of the liver, sinuses and red pulp of the spleen, and the bone marrow. The tumour cells express CD2 and CD3, but are CD4, CD5 and CD8 negative and express a clonally restricted gamma-delta (or less commonly alpha-beta) T-cell receptor. The disease has an aggressive clinical course associated with a poor prognosis. We highlight and report three patients from South Africa with HSTCL, all of whom had hepatosplenomegaly and cytopaenias, and despite being HIV seronegative and immunocompetent, had a poor outcome, with a mean survival of 7.5 months in the two evaluable patients. This rare entity has not previously been reported from South Africa and as yet needs to be adequately characterised in a population where lymphoma is the most common haematological malignancy in adults, and where approximately two thirds of the adult lymphoma population are HIV seropositive.

The spectrum of HIV-associated cancers in a South African black population: results from a case-control study, 1995–2004

Accumulating evidence confirms different patterns of HIV-associated cancers in developed and developing countries. We report results of risk for specific cancers associated with HIV-1 infection from an on-going case control study started in government hospitals in Johannesburg in 1995. Cases consisted of cancers known or suspected to be associated with HIV infection: Kaposi sarcoma (n = 333), Non-Hodgkin lymphoma (n = 223), cancer of the uterine cervix (n = 1586), Hodgkin lymphoma (n = 154), cancers of anogenital organs other than cervix (n = 157), squamous cell skin cancer (n = 70), oral cavity and pharyngeal cancers (n = 319), liver cancer (n = 83), stomach cancer (n = 142), leukaemias (n = 323), myelomas (n = 189), melanoma (n = 53), lung cancer (n = 363) and sarcomas other than Kaposi (n = 93). The comparison group comprised 3,717 patients with all other cancer types and 682 patients with cardiovascular diseases. Odds Ratios (OR) were adjusted for age, sex, year of diagnosis, education level and number of sexual partners. Significantly increased risks associated with HIV-1 infection were found for Kaposi sarcoma (OR = 47.1, 95% CI = 31.9 – 69.8), Non-Hodgkin lymphoma (OR = 5.9, 95% CI = 4.3 – 8.1), cancer of the cervix (OR = 1.6, 95% CI = 1.3 – 2.0), Hodgkin lymphoma (OR = 1.6, 95% CI = 1.0 – 2.7), cancers of anogenital organs other than cervix (OR = 2.2, 95% CI = 1.4 – 3.3) and squamous cell skin cancers (OR = 2.6, 95% CI = 1.4 – 4.9). Our study results are supported by data from the pathology-based South African National Cancer Registry. In 2001 Kaposi sarcoma was recorded as the leading cancer in black males age 20 to 44 and in black females aged 20 to 29. From age 30, cervical cancers was the most common cancer diagnosed in black women. The above figures reflect HIV-related cancers prior to the public health sector roll-out of ART (anti-retroviral therapy), which began in 2005.