Estimating the changing disease burden attributable to smoking in South Africa for 2000, 2006 and 2012.

BACKGROUND: Ongoing quantification of the disease burden attributable to smoking is important to monitor and strengthen tobacco control policies. OBJECTIVES: To estimate the attributable burden due to smoking in South Africa for 2000, 2006 and 2012. METHODS: We estimated attributable burden due to smoking for selected causes of death in South African (SA) adults aged ≥35 years for 2000, 2006 and 2012. We combined smoking prevalence results from 15 national surveys (1998 - 2017) and smoking impact ratios using national mortality rates. Relative risks between smoking and select causes of death were derived from local and international data. RESULTS: Smoking prevalence declined from 25.0% in 1998 (40.5% in males, 10.9% in females) to 19.4% in 2012 (31.9% in males, 7.9% in females), but plateaued after 2010. In 2012 tobacco smoking caused an estimated 31 078 deaths (23 444 in males and 7 634 in females), accounting for 6.9% of total deaths of all ages (17.3% of deaths in adults aged ≥35 years), a 10.5% decline overall since 2000 (7% in males; 18% in females). Age-standardised mortality rates (and disability-adjusted life years (DALYs)) similarly declined in all population groups but remained high in the coloured population. Chronic obstructive pulmonary disease accounted for most tobacco-attributed deaths (6 373), followed by lung cancer (4 923), ischaemic heart disease (4 216), tuberculosis (2 326) and lower respiratory infections (1 950). The distribution of major causes of smoking-attributable deaths shows a middle- to high-income pattern in whites and Asians, and a middle- to low-income pattern in coloureds and black Africans. The role of infectious lung disease (TB and LRIs) has been underappreciated. These diseases comprised 21.0% of deaths among black Africans compared with only 4.3% among whites. It is concerning that smoking rates have plateaued since 2010. CONCLUSION: The gains achieved in reducing smoking prevalence in SA have been eroded since 2010. An increase in excise taxes is the most effective measure for reducing smoking prevalence. The advent of serious respiratory pandemics such as COVID-19 has increased the urgency of considering the role that smoking cessation/abstinence can play in the prevention of, and post-hospital recovery from, any condition.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.

INTRODUCTION: The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design. MATERIAL AND METHODS: Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases. RESULTS: 10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer. DISCUSSION: This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.

Effects of tobacco smoking on cancer and cardiovascular disease in urban black South Africans.

Demographic and lifestyle information from 9690 black patients diagnosed with cancer or cardiovascular disease was collected in an ongoing case-control study in Johannesburg, South Africa. Compared to never smokers, the odds ratio (OR) for lung cancer among current smokers was 16.3 (95% confidence interval (CI), 9.6-27.6) for men and 6.4 (95% CI, 4.0-10.4) for women. The corresponding OR for other smoking-related cancers was 4.6 (95% CI, 3.7-5.7) among men and 1.9 (95% CI, 1.6-2.2) among women, and for cardiovascular disease, 3.4 (95% CI, 2.1-5.4) among men and 1.5 (95% CI, 1.1-2.1) among women. Risks were higher among smokers than former smokers, and all risk estimates increased with increasing levels of smoking duration and intensity. Non-electric domestic fuel was associated with approximately 60% increase in the risk of smoking-related cancer, but not cardiovascular disease. Risks for cancers of cervix, oesophagus, oral cavity/pharynx, stomach, larynx, pancreas and anogenital region, as well as squamous cell carcinoma of skin were all significantly higher among current than never-smokers, with ORs ranging from 1.5 for cervix (95% CI, 1.2-1.8) to 14.7 for larynx (95% CI, 7.2-30). The risks of tobacco-related disease reported here are similar to that currently observed in Western countries, even though cigarette consumption is relatively low in this population.

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: a case control study.

BACKGROUND: Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. METHODS: We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity (n = 88), the cervix (n = 53), the prostate (n = 66), Hodgkin lymphoma (n = 83), non-Hodgkin lymphoma (n = 80), multiple myeloma (n = 94) or leukaemia (n = 203). For comparison, patients with other cancers (n = 95) or cardiovascular disease (n = 101) were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. RESULTS: There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0.02, respectively). Odds ratios for the top tertile compared to the bottom tertile were 0.58 (95%CI 0.3-1.0) for myeloid leukaemia and 2.21 (95% CI 1.1-4.3) for oral cancer. CONCLUSION: In this population, using these tests for IgG, neither mean antibody measure nor high antibody measure against human herpesviruses 1-6 was strongly associated with any of the seven cancer groups. However, we may not have had sufficient power to detect weak associations or associations with a sub-type of cancer if they were present.

Tobacco attributable deaths in South Africa.

BACKGROUND: In mid 1998, a question "Was the deceased a smoker five years ago?" was introduced on the newly revised South African death notification form. DESIGN: A total of 16,230 new death notification forms from 1998 have been coded, and comparison of the prevalence of smoking among those who died of different causes was used to estimate, by case-control comparisons, tobacco attributed mortality in South Africa. Cases comprised deaths from causes known (from other studies) to be causally associated with smoking, and controls comprised deaths from medical conditions expected to be unrelated to smoking. Those who died from external causes, and from diseases strongly related to alcohol consumption, were excluded. SUBJECTS: Reports were available from 5340 deceased adults (age 25+), whose smoking status was given by a family member. RESULTS: Significantly increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0), other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart disease (OR 1.7, 95% CI 1.2 to 2.3). CONCLUSION: If smokers had the same death rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8% of all adult deaths in South Africa (more than 20 000 deaths a year) were caused by smoking.

Antibodies against human herpesvirus 8 in South African renal transplant recipients and blood donors.

OBJECTIVE: To examine the seroprevalence of human herpesvirus 8 (HHV-8) antibodies in a selected group of renal transplant recipients and blood donors, in relation to various socio-demographic variables. SUBJECTS: Anonymised serum samples were obtained from 306 black donors attending blood donations at the SA National Blood Transfusion Service, Johannesburg, and 430 recipients of renal transplants at Johannesburg General Hospital, from 1998 to 1999. METHODOLOGY: Serum samples were tested by indirect immunofluorescence assay to detect IgG antibodies against HHV-8. Crude and adjusted seroprevalence, and odds ratios were calculated to examine the relationship between antibodies to HHV-8 and age, sex, population, and risk group. RESULTS: Adjusted HHV-8 seroprevalence at 'medium to high' antibody titres (at least 1:51,200) increased with age, from 2% (age 15-24; 95% CI=0.7-5.2) to 10% (age 45+; 95% CI=6.3-15.2). Whites had the lowest % adjusted seroprevalence (1.8; 95% CI:0.8-4.2), followed by blacks (7.4; 95% CI=5.1-10.8), Asians/Indians (9.5; 95% CI=3.6-22.9), and individuals of mixed race (12.5; 95% CI=4.5-30.2). Seroprevalence was not related to gender, or to occupation of blood donors. HHV-8 seroprevalence did not differ significantly between first-time blood donors, repeat donors, and transplant recipients (P=0.49). Transplant recipients had a greater proportion of persons with high HHV-8 antibody intensity; however, this difference was statistically not significant (P=0.08). CONCLUSIONS: Blood donors and renal transplant patients had relatively high HHV-8 antibody titres. Given the strong association between HHV-8 seropostivity and the risk of developing Kaposi's sarcoma, it may be prudent in settings where HHV-8 seroprevalence is high to screen for HHV-8 in donated blood used for these immunocompromised individuals.

Low socioeconomic status and risk for infection with human herpesvirus 8 among HIV-1 negative, South African black cancer patients.

Between January 1994 and October 1997, we interviewed 2576 black in-patients with newly diagnosed cancer in Johannesburg and Soweto, South Africa. Blood was tested for HIV-1 and HHV-8 antibodies and the study was restricted to 2191 HIV-1 antibody-negative patients. We examined the relationship between infection with HHV-8 and sociodemographic and behavioural factors using unconditional logistic regression models. Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.1%) were positive for antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 in a immunofluorescence assay. Infection with HHV-8 was independently associated with increasing age (P trend = 0.02). For females, independent risk factors also included working in a paid domestic capacity (OR 1.63, 95% CI 1.09-2.44, P = 0.02), defining occupational status as economically non-active unemployed (OR 1.70, 95% CI 1.06-2.72, P = 0.03), having a state pension or being on a disability grant (OR 1.49, 95% CI 1.05-2.11, P = 0.02), using oral contraceptives (OR 1.43, 95% CI 1.03-1.99, P = 0.03) and having a delayed age at menarche (P trend = 0.04). The relationship between these variables and HHV-8 antibody status requires further, prospective study.

Human herpesvirus-8 antibodies and DNA in HIV-1 infected patients in South Africa.

HIV-infected individuals with high levels of IgG antibodies against human herpesvirus-8 (HHV-8) are at increased risk of developing Kaposi's sarcoma. The aim of this study was to measure the association between HHV-8 viraemia and IgG antibody responses (by immunofluorescence) in a group of 201 HIV-infected individuals attending outpatient clinics, 91 in-patients with AIDS and 87 HIV-infected patients admitted with Kaposi's sarcoma. Compared to HIV-infected outpatients, the adjusted odds ratio in relation to Kaposi's sarcoma was 15.4 (95% CI 4.4-54.2) in those with viraemia, 25.1 (95% CI 6.6-95.6) in those with a positive immunofluorescent signal and infinity (lower exact CI 33.6) in those with a high immunofluorescent signal (all P trend < 0.001). Among those without HHV-8 viraemia, 23% were IgG-positive, but only 5.5% had a high immunofluorescent signal. In those who were viraemic, 89.1% were IgG-positive, and 28.2% had a high immunofluorescent signal, suggesting viraemia is associated with high HHV-8 immunofluorescence IgG signal.

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.

A minimum estimate for the incidence of gastric cancer in Eastern Kenya.

We documented available information concerning incident cases of gastric cancer in part of Kenya's Eastern Province between 1991 and 1993. By reviewing the records of all major health facilities in the area, 200 cases of gastric carcinoma were found giving an annual average crude incidence rate of 7.01 per 100 000 males and 3.7 for females (world age-standardised rates, 14.3 for males and 7.1 for females). There is likely to be underascertainment of cases especially among those aged over 65 years. Previous incidence estimates for the same area of Kenya were reviewed and a 10-fold increase in the recorded indirectly standardised incidence rate between the periods 1965-70 and 1991-93 was noted but this may be due to improved diagnostic facilities. The recent rates in this part of Kenya are comparable to Eastern European rates and similar to those recorded in other highland regions of Africa.

Breast cancer incidence in South Africa.

Cancer in South Africa is an emerging health problem, with breast cancer being one of the leading cancers in women, following similar worldwide statistics. Lifetime risks of developing breast cancer vary from a low of one in 81 in African women (similar to Japan) to a high of one in 13 among white women, similar to rates in Western countries. Age and stage at diagnosis vary considerably between the different races and populations (urban v rural) living in South Africa. Many different determinants (socioeconomic, cultural, geographic accessibility to medical centers with oncologic services, availability of traditional healers, and so on) affect patients with breast cancer (mainly rural black women) in their decisions to obtain early medical help as well as to refrain from the proposed therapeutic methods (surgery, radiotherapy, and chemotherapy). A brief overview of breast cancer in South Africa with special reference to some of the above determinants is presented.

Kaposi's sarcoma in South Africa.

Kaposi's sarcoma was endemic in South Africa even before the advent of the human immunodeficiency virus (HIV). Between 1988 and 1996, the incidence of Kaposi's sarcoma in South Africa has risen at least threefold and continues to increase as the HIV epidemic grows. Research from South Africa has shown that infection with human herpesvirus 8 (HHV8) is associated with Kaposi's sarcoma but not with any other major cancer site or type. In addition, the risk of Kaposi's sarcoma increases with increasing antibody titer to HHV8, but, for a given titer, the risk is greater in HIV-seropositive compared with HIV-seronegative individuals. The age- and sex-standardized seroprevalence of HHV8 in black South African hospital patients was found to be slightly more than 30%; the seroprevalence of HHV8 increased with age and was similar in men and in women. The modes of transmission of HHV8 are yet to be fully elucidated. Limited evidence exists for sexual transmission in black South African adults, but mother-to-child and person-to-person transmission in childhood is also likely. Furthermore, the seroprevalence of HHV8 decreases with increasing levels of education and is lower in whites than in blacks, suggesting that factors associated with poverty may be important determinants of transmission. Future research should focus on risk factors for Kaposi's sarcoma in HHV8-infected individuals, on determinants and mode of transmission of HHV8, and on the elucidation of the effect of primary HHV8 infection in adults and in children.

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 Kaposi's 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 Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

Antibodies against human herpesvirus 8 in black South African patients with cancer.

BACKGROUND: Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. METHODS: Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti-HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV infection were examined with the use of unconditional logistic-regression models. RESULTS: Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti-HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti-HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1-positive patients than among those who were HIV-1-negative (P<0.001). CONCLUSIONS: Among black patients with cancer in South Africa, the seroprevalence of anti-HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

Lung cancer, tobacco, and environmental factors in the African population of the Northern Province, South Africa.

DESIGN: Case-control study among incident African patients with cancer. Questionnaire assessment of exposure to tobacco, occupation, and place of birth. SETTING: Northern Province, South Africa. SUBJECTS: Between 1993 and 1995, 288 men and 60 women with lung cancer and 183 male and 197 female controls (consisting of patients newly diagnosed with cancers other than those known to be associated with smoking) were interviewed. Unmatched, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of developing lung cancer in relation to a number of variables. MAIN OUTCOME MEASURE: Risk of developing lung cancer related to exposure to tobacco, indoor pollution, dusty work environment, and residential exposure to asbestos. RESULTS: There was a significant increase in the risk of developing lung cancer through smoking. In men, the ORs were 2.2 (95% CI = 1.0 to 4. 6) in ex-smokers, 9.8 (95% CI = 5.9 to 16.4) in light smokers (0-14 g/day), and 12.0 (95% CI = 6.5 to 22.3) in heavy smokers. In women, the ORs were 5.8 (95% CI = 1.3 to 25.8) in ex-smokers and 5.5 (95% CI = 2.6 to 11.3) in current smokers. Work in a dusty industry showed an elevated risk (OR = 3.2, 95% CI = 1.8 to 5.8) for lung cancer only in men. Male residents of areas where asbestos was shipped for distribution (termed moderately polluted asbestos areas) had a 2.5-fold increase (95% CI = 1.0 to 4.4) in the risk (OR) of developing lung cancer, and residents of areas where asbestos was mined (termed heavily polluted asbestos areas) had a 2.8-fold increase in risk (95% CI = 0.7 to 10.4). Female residents of heavily polluted asbestos areas showed elevated risks of 5.4 (95% CI = 1.3 to 22.5) of developing lung cancer. CONCLUSION: The data suggest that tobacco smoking is the most important risk factor for the development of lung cancer in this setting. Risks for lung cancer are reminiscent of those observed in Western countries in the 1960s and 1970s. However, environmental exposure to asbestos, a dusty occupation (in men), and perhaps indoor air pollution may also contribute to the development of lung cancer in this province.