Paola Pisani

Estimating the world cancer burden : GLOBOCAN 2000

Describing the distribution of disease between different populations and over time has been ahighly successfu l way of devising hypothese s about causation and for quantifying the potential for preventive activities.1 Statistical data are also essentia l componentsof diseasesurveillanceprograms. Theseplay acritical role in the developmen t and implementation of health policy, through identification of health problems, decisions on priorities for preventive and curative programs and evaluation of outcomes of programs of prevention, early detection/screenin g and treatment in relation to resource inputs. Over the last 12 years, aseries of estimates of the global burden of cancer have been published in the International Journal of Cancer. 2–6 The methods have evolved and been refined, but basically they rely upon the best availabl e data on cancer incidence and/or mortality at country level to build up theglobal picture. The results are more or less accurat e for different countries, depending on the extent and accuracy of locally availabl e data. This “databased” approach is rather different from themodeling method used in other estimates. 7–10 Essentially, these use sets of regression models, which predict cause-specifi c mortality rates of different populations from the correspondin g all-cause mortality.11 The constant s of the regression equations derive from dataset s with different overal mortality rates (often including historic data from wester n countries) . Cancer deaths are then subdivided into the different cancer types, according to the best availabl e information on relative frequencies. GLOBOCAN 2000 updates thepreviousl y published data-based global estimates of incidence, mortality and prevalence to the year 2000.12

Estimates of the worldwide incidence of 25 major cancers in 1990.

The annual incidence rates (crude and age‐standardized) and numbers of new cases of 25 different cancers have been estimated for the year 1990 in 23 areas of the world. The total number of new cancer cases (excluding non‐melanoma skin cancer) was 8.1 million, just over half of which occur in the developing countries. The most common cancer in the world today is lung cancer, accounting for 18% of cancers of men worldwide, and 21% of cancers in men in the developed countries. Stomach cancer is second in frequency (almost 10% of all new cancers) and breast cancer, by far the most common cancer among women (21% of the total), is third. There are large differences in the relative frequency of different cancers by world area. The major cancers of developed countries (other than the 3 already named) are cancers of the colon‐rectum and prostate, and in developing countries, cancers of the cervix uteri and esophagus. The implications of these patterns for cancer control, and specifically prevention, are discussed. Tobacco smoking and chewing are almost certainly the major preventable causes of cancer today.Int. J. Cancer 80:827–841, 1999.

Estimates of the worldwide mortality from 25 cancers in 1990

We present here worldwide estimates of annual mortality from all cancers and for 25 specific cancer sites around 1990. Crude and age‐standardised mortality rates and numbers of deaths were computed for 23 geographical areas. Of the estimated 5.2 million deaths from cancer (excluding non‐melanoma skin cancer), 55% (2.8 million) occurred in developing countries. The sex ratio is 1.33 (M:F), greater than that of incidence (1.13) due to the more favourable prognosis of cancer in women. Lung cancer is still the most common cause of death from cancer worldwide with over 900,000 deaths per year, followed by gastric cancer with over 600,000 deaths and colorectal and liver cancers accounting for at least 400,000 deaths each. In men, deaths from liver cancer exceed those due to colo‐rectal cancer by 38%. Over 300,000 deaths of women are attributed to breast cancer, which remains the leading cause of death from cancer in women, followed by cancers of the stomach and lung with 230,000 annual deaths each. In men, the risk of dying from cancer is highest in eastern Europe, with an age‐standardised rate for all sites of 205 deaths per 100,000 population. Mortality rates in all other developed regions are around 180. The only developing area with an overall rate of the same magnitude as that in developed countries is southern Africa. All of eastern Asia, including China, has mortality rates above the world average, as do all developed countries. The region of highest risk among women is northern Europe (age‐standardised rate = 125.4), followed by North America, southern Africa and tropical South America. Only south‐central and western Asia (Indian subcontinent, central Asia and the middle‐eastern countries) and Northern Africa are well below the world average of 90 deaths per 100,000 population annually. Our results indicate the potential impact of preventive practices. It is estimated that 20% of all cancer deaths (1 million) could be prevented by eliminating tobacco smoking. Infectious agents account for a further 16% of deaths. Int. J. Cancer 83:18–29, 1999.

Genetic pathways to glioblastoma: a population-based study.

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C→A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Overweight as an avoidable cause of cancer in Europe

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post‐menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta‐analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex‐specific estimates of the prevalence of overweight [body mass index (BMI) 25–29 kg/m2] and obesity (BMI ≥30 kg/m2) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

Estimates of the world‐wide prevalence of cancer for 25 sites in the adult population

In health services planning, in addition to the basic measures of disease occurrence incidence and mortality, other indexes expressing the demand of care are also required to develop strategies for service provision. One of these is prevalence of the disease, which measures the absolute number, and relative proportion in the population, of individuals affected by the disease and that require some form of medical attention. For most cancer sites, cases surviving 5 years from diagnosis experience thereafter the same survival as the general population, so most of the workload is therefore due to medical acts within these first 5 years. This article reports world‐wide estimates of 1‐, 2–3‐ and 4–5‐year point prevalence in 1990 in the population aged 15 years or over, and hence describes the number of cancer cases diagnosed between 1986 and 1990 who were still alive at the end of 1990. These estimates of prevalence at 1, 2–3 and 4–5 years are applicable to the evaluation of initial treatment, clinical follow‐up and point of cure, respectively, for the majority of cancers. We describe the computational procedure and data sources utilised to obtain these figures and compare them with data published by 2 cancer registries. The highest prevalence of cancer is in North America with 1.5% of the population affected and diagnosed in the previous 5 years (about 0.5% of the population in years 4–5 and 2–3 of follow‐up and 0.4% within the first year of diagnosis). This corresponds to over 3.2 million individuals. Western Europe and Australia and New Zealand show very similar percentages with 1.2% and 1.1% of the population affected (about 3.9 and 0.2 million cases respectively). Japan and Eastern Europe form the next batch with 1.0% and 0.7%, followed by Latin America and the Caribbean (overall prevalence of 0.4%), and all remaining regions are around 0.2%. Cancer prevalence in developed countries is very similar in men and women, 1.1% of the sex‐specific population, while in developing countries the prevalence is some 25% greater in women than men, reflecting a preponderance of cancer sites with poor survival such as liver, oesophagus and stomach in males. The magnitude of disease incidence is the primary determinant of crude prevalence of cases diagnosed within 1 year so that differences by region mainly reflect variation in risk. In the long‐term period however different demographic patterns with long‐life expectancy in high‐income countries determine a higher prevalence in these areas even for relatively uncommon cancer sites such as the cervix.

Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand

Liver cancer is the most common cancer in Khon Kaen, Northeast Thailand, because of the high incidence of cholangiocarcinoma (CHCA). Opisthorchis viverrini (OV), a liver fluke, is endemic in the area, and has been evaluated as a cause of CHCA by International Agency for Research on Cancer. Residents of 20 districts in the province were invited to attend a mobile screening programme between 1990 and 2001. Of 24 723 participants, 18 393 aged 35–69 years were tested for OV infection, by examining stools for the presence of eggs. Prevalence of infection in each district was estimated from the sample of the population who had been tested. The incidence of liver cancer in 1990–2001 was obtained for each district from the cancer registry. The average crude prevalence of OV infection in the sample subjects was 24.5%, ranging from 2.1% to 70.8% in different districts. Truncated age‐standardized incidence of CHCA at ages >35 years varied threefold between districts, from 93.8 to 317.6 per 100 000 person‐years. After adjustment for age group, sex and period of sampling, there was a positive association between prevalence of OV infection and incidence of CHCA at the population level. Associations between CHCA and active OV infection in individuals have become hard to demonstrate, because of effective anti‐OV treatment. The relationship may, however, be clear in comparisons between populations, which, for infectious diseases, take into account the contextual effects of group exposure in determining individual outcome. The cancer registry is an appropriate tool for disease monitoring in small areas.

Outcome of screening by clinical examination of the breast in a trial in the Philippines

The value of screening by Clinical Examination of the Breast (CBE) as a means of reducing mortality from breast cancer (BC) is not established. The issue is relevant, as CBE may be a suitable option for countries in economic transition, where incidence rates are on the increase but limited resources do not permit screening by mammography. Our aims were to assess whether mass screening by CBE carried out by trained para‐medical personnel is feasible in an urban population of a low‐income country, and its efficacy in reducing BC mortality. Our study was designed as a randomised controlled trial of the effect on BC mortality of 5 annual CBE carried out by trained nurses. The target population was women aged 35–64 years, resident in 12 municipalities of the National Capital Region of Manila, Philippines. The units of randomization were the 202 health centres (HC) within the selected municipalities. During 1995 nurses and midwives were recruited and trained in performing CBE. The first round of screening took place in 1996–1997. The intervention however showed a refractory attitude of the population with respect to clinical follow‐up and was discontinued after the completion of the first screening round. Cases of breast cancer occurring in the study population during 1996–1999 were identified by the 2 local population‐based registries. In the single screening round 151,168 women were interviewed and offered CBE, 92% accepted (138,392), 3,479 were detected positive for a lump and referred for diagnosis. Of these only 1220 women (35%) completed diagnostic follow‐up, whereas 42.4% actively refused further investigation even with home visits, and 22.5% were not traced. Of 53 cases that occurred among screen‐positive women in the 2 years after CBE only 34 were diagnosed through the intervention. Eighty cases occurred among screen‐negative women. The test sensitivity for CBE repeated annually was 53.2%. The actual sensitivity of the programme was 25.6% and positive predictive value 1%. Screen‐detected cases were non‐significantly less advanced than the others. Previous studies have shown that most breast cancer cases in the Philippines present at advanced stages and have an unfavourable outcome. Although CBE undertaken by health workers seems to offer a cost‐effective approach to reducing mortality, the sensitivity of the screening programme in the real context was low. Moreover, in this relatively well‐educated population, cultural and logistic barriers to seeking diagnosis and treatment persist and need to be addressed before any screening programme is introduced.

Environmental exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis Environmental exposure to asbestos and mesothelioma

A number of epidemiological studies have addressed the risk of pleural mesothelioma from environmental (household and neighborhood) exposure to asbestos, but no overall risk estimate is available. We reviewed the epidemiological studies on risk of pleural mesothelioma and household or neighborhood exposure to asbestos. We identified eight relevant studies; most were conducted in populations with relatively high exposure levels. We combined the risk estimates in a meta-analysis based on the random-effects model. The relative risks (RRs) of pleural mesothelioma for household exposure ranged between 4.0 and 23.7, and the summary risk estimate was 8.1 (95% confidence interval [CI]: 5.3–12). For neighborhood exposure, RRs ranged between 5.1 and 9.3 (with a single RR of 0.2) and the summary estimate was 7.0 (95% CI: 4.7–11). This review suggests a substantial increase in risk of pleural mesothelioma following high environmental exposure to asbestos; however, the available data are insufficient to estimate the magnitude of the excess risk at the levels of environmental exposure commonly encountered by the general population in industrial countries.

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India

Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster‐randomized, controlled oral cancer screening trial in southern India and its early results.