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.

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.

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.

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.

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.

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.

Serum anti-Helicobacter pylori IgG antibodies and pepsinogens A and C as serological markers of chronic atrophic gastritis.

This study was designed to test the sensitivity and specificity of serum anti-Helicobacter pylori IgG antibodies and the ratio of serum pepsinogen A to pepsinogen C (PGA:PGC) in detecting chronic atrophic gastritis (CAG) and intestinal metaplasia. Parallel gastric biopsies and a serum sample were collected from a series of 87 patients aged 20-69 years attending a routine upper endoscopy clinic. The seroprevalence (> 10 micrograms IgG/ml) of anti-H. pylori antibodies was 42.7%, and of a low PGA:PGC ratio (< 1.5) was 17.7%. A positive H. pylori IgG antibody level was more sensitive than the level of PGA:PGC in diagnosing CAG (71.4% and 25.0%, respectively), moderate CAG (86.7% and 26.7%, respectively), and intestinal metaplasia (90.9% and 50.0%, respectively). Anti-H. pylori IgG antibody levels were less specific than PGA:PGC levels in diagnosing CAG (90.9% and 93.9%, respectively), moderate CAG (78.3% and 89.1%, respectively), and intestinal metaplasia (72.6% and 92.2%, respectively). A combination of anti-H. pylori antibodies and a low PGA:PGC ratio for the detection of CAG resulted in a specificity of 100%, but the sensitivity was 21.4%.

Helicobacter pylori antibodies in areas of Italy at varying gastric cancer risk.

In a survey of 930 adults aged 35-74 years randomly sampled from the general population of four areas of Italy, two at low and two at high risk for gastric cancer, plasma levels of Helicobacter pylori IgG antibodies were assayed in order to investigate associations with the geographical distribution of gastric cancer and other dietary and life-style factors, as assessed by personal interview. H. pylori positivity (antibody titer above or equal to 10 micrograms/ml), 45% overall, increased with age and was inversely associated with social class but showed little geographical variation or association with dietary variables and blood nutrients. H. pylori positivity was also associated with increased blood levels of pepsinogens, particularly pepsinogen II. The authors discuss these findings in relation to those from a previous case-control study of gastric cancer in the same areas.

Respiratory questionnaires in occupational studies: their use in multilingual workforces on the Witwatersrand.

The mother tongue of the majority of black workers in the industrial workforces of the Witwatersrand is either Zulu or S Sotho/Tswana, and these are also the main languages spoken in the area. However a substantial minority cite one of several other languages as their mother tongue. In consequence, in occupational surveys using a respiratory questionnaire, the accepted practice has been to use multilingual interviewers who administer the questionnaire in whichever of the two main languages the interviewee requests, but work from an English language version. To test the reproducibility of the information so gathered, a standardized questionnaire was administered to 56 subjects on two occasions approximately three weeks apart by each of two interviewers, one of whose mother tongue was Zulu and the other S Sotho. Reproducibility was little affected by whether the interviewer used her mother tongue or not, pointing to the multilingual competence of both interviewers. Reproducibility was, however, less in subjects not interviewed in their mother tongue compared to those who were. In general, reproducibility was also less for symptom than for history questions, though the phlegm question performed comparably to that reported for more homogeneous language/ethnic groups. Thus, even if internally valid, respiratory symptom information obtained by this method may have limited generalizability. However respiratory history information appears more reliable and may prove of value in the investigation of the natural history of chronic lung disease in this and similar communities.

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.

Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation.

OBJECTIVE: To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN: Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS: 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS: 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS: H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.

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.

Histologically diagnosed cancers in South Africa, 1988.

The National Cancer Registry (NCR) collects information on cancer diagnoses via a nation-wide network of public and private pathology laboratories. In 1988, 45,570 new laboratory-diagnosed cancer cases were reported to the NCR. Minimal age-standardised registration rates for black, white, coloured and Asian males were 112.2, 229.9, 192.2 and 91.6/100,000, respectively, and those for females 107.2, 201.3 148.1 and 118.0. About 40% of cancers in females and 31.3% in males occurred in potentially economically active adults aged 15-54 years. The top five cancers in males were: (i) basal cell skin cancer; (ii) cancer of the prostate gland; (iii) cancer of the oesophagus; (iv) lung cancer; and (v) squamous cell skin cancer. In females they were: (i) cancer of the cervix; (ii) breast cancer; (iii) basal cell skin cancer; (iv) squamous cell skin cancer; and (v) cancer of the oesophagus. Despite under-reporting, a number of cancers, especially those of the oesophagus and cervix in blacks and skin cancers in whites, rank among the highest in the world. Moreover, 40.4% of the cancers in adult males (15-64 years) and 15.2% of those in adult females were associated with tobacco use.(ABSTRACT TRUNCATED AT 250 WORDS)

Some observations on a cholera outbreak at the Umvoti Mission Reserve, Natal.

Between November 1981 and January 1982 154 consecutive patients with cholera El Tor Inaba were hospitalized at Stanger Hospital, Natal. These cases were traced to 130 households in the Umvoti Mission Reserve, which were ranked according to socioeconomic condition, permanence of housing materials, ablution facilities and purity of water source. Significant associations were found between cholera incidence and both socio-economic conditions and water source; the latter two were also strongly associated. In a number of instances the outbreak did not follow the downstream flow of the rivers. Increased mobility and social gathering over the holiday season appears to have played a role in transmission. The atypical pattern of spread may also have resulted from non-water-borne, person-to-person transmission.

Geographical epidemiology of prostate cancer: is there an association with infection?

Incidence and mortality data from the 1960s, when screening for cancers of the cervix and prostate was minimal, reveal a positive but statistically nonsignificant geographical association between the two diseases. Data on cancer incidence from African cancer registries and from the South African National Cancer Registry also show weak but positive associations. To determine whether infection is a cause of prostate cancer, case-control studies need to be conducted on individuals with and without prostate cancer or prostate cancer precursors. The screening of serum for prostate specific antigen provides an excellent opportunity to test for sexually transmitted agents.

Histologically diagnosed cancer in South Africa, 1987.

The National Cancer Registry collects information on cases of histologically diagnosed cancer via a country-wide network of private and public pathology laboratories. Minimal age-standardised incidence rates (ASIR, world standard) per 100,000, excluding basal and squamous cell skin cancers, for white, coloured and Asian males were 195.9, 76.2 and 82.9 respectively, and for females 161.8, 68.8 and 81.1 respectively. The oesophagus was the commonest site of cancer in black males, comprising 25.2% of all cancers in this group, and the cervix was the commonest site in black females (31.6%). Basal and squamous cell skin cancers were the leading cancers in white males (ASIR 191.9) and females (ASIR 96.9). Despite limitations, especially in data for blacks, rates for oesophageal, cervical and skin cancers rank among the highest in the world. The lung was the leading site of cancer in coloured males (ASIR 13.8) but this cancer is underestimated in all populations. Reasons for underestimation of cancer incidence include the use of non-histological methods for diagnosing cancer (cytology, radiographs, clinical examination) and variable access of populations, especially blacks and coloureds, to laboratory diagnostic facilities.

A role for the ecological study in the developing world.

Retrospective case-control or prospective (follow-up) studies are important epidemiological tools and have provided useful information on exposure disease associations. Prospective studies would be the ideal option, but many countries (particularly in the developing world) do not have the necessary infrastructure to follow people up. Both retrospective and prospective studies are, however, sometimes conducted without due regard for their own limitations. These limitations are exacerbated when measures of exposure or disease are based on a single measurement and where the population under study is homogeneous with regard to exposure. The former is responsible for regression dilution bias and the latter for a lack of contrasts between exposure groups. Both factors would attenuate any relationship between exposure and disease. Ecological studies in epidemiology are weaker in design than case-control or prospective studies, but in some circumstances an ecological approach, which looks at the prevalence of an exposure or disorder in a number of areas of varying disease rates, may offer some advantages.

The level of mortality in South Africa in 1985--what does it tell us about health?

South African mortality data are inadequate for health planning. Estimates of mortality levels in blacks for 1985, derived using indirect demographic techniques, have provided an opportunity to analyse South African mortality in a health context. The infant mortality rate (IMR) for the population as a whole was 64/1,000 live births in 1985, which is high when compared with those of other countries. The IMR varied between population groups and was highest in blacks (males 73, females 68) and lowest in whites (males 11, females 7). Adult mortality rates, measured in terms of the chance of a 15-year-old dying before reaching the age of 60, ranged from 42.8% for black males and 29.4% for black females, to 21.8% and 11.5% for white males and females respectively. Life expectancy at birth of black males and females was 55 and 61 years respectively, while for white males and females it was 68 and 76 years respectively. Infectious diseases are a leading cause of death in blacks under 5 years of age, while trauma, poverty-related diseases and chronic diseases related to lifestyle all contribute to the high levels of adult mortality in this group. Prevention and health promotion strategies focusing on these as well as HIV/AIDS must be incorporated in a primary health care strategy to reduce premature mortality. Most importantly, it is crucial to improve the registration system that is vital to facilitate ongoing evaluation.

Residual risk of transmission of HIV through blood transfusion in South Africa.

Despite the ongoing review of donor recruitment criteria by local blood transfusion services and the development of highly sensitive and specific testing for the presence of antibodies to HIV in blood and blood products, there remains a residue of HIV in donated blood. This is because of donors who are in the 'window period' between acquisition of HIV and seroconversion, human errors and limits to the sensitivity and specificity of current tests. Data available from a national survey of HIV seroprevalence in South African blood donors allowed for the estimation of the number of units screened negative but likely to be infected with HIV. Assuming window periods of 4.8 and 14 weeks, a test sensitivity of 99.9%, a specificity of 98.5% and a human error rate of 0.1%, the likely rate of HIV-infected blood in the South African blood transfusion supply ranges from 1.1 to 3.9/100,000 units, with a likely estimate of 2.2/100,000 units. In the current South African blood transfusion setting, between 8.1 and 28.2 units of blood per annum will be HIV-positive with a likely estimate of 15.9 units. This corresponds to an odds ratio of between 1:90 909 and 1:25 641 units infected with HIV. These data are comparable with the risk in developed countries. The expected increase in the incidence and prevalence of HIV infection in all adult South African populations necessitates additional measures to ensure a blood supply which is as safe as possible. Some of these measures have already been taken by local blood transfusion services.