PII: S1470-2045(01)00486-7


Published on

  • Be the first to comment

  • Be the first to like this

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

PII: S1470-2045(01)00486-7

  1. 1. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 533 Global cancer statistics in the year 2000 D Maxwell Parkin Estimation of the burden of cancer in terms of incidence, mortality, and prevalence is a first step to appreciating appropriate control measures in a global context. The latest results of such an exercise, based on the most recent available international data, show that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer in 2000. The most common cancers in terms of new cases were lung (1.2 million), breast (1.05 million), colorectal (945 000), stomach (876 000), and liver (564 000). The profile varies greatly in different populations, and the evidence suggests that this variation is mainly a consequence of different lifestyle and environmental factors, which should be amenable to preventive interventions. World population growth and ageing imply a progressive increase in the cancer burden – 15 million new cases and 10 million new deaths are expected in 2020, even if current rates remain unchanged. Lancet Oncol 2001; 2: 533–43 Globalisation implies more than the application of market capitalism free from constraint by local or national authority. Health and disease are increasingly seen in a global context, and a proliferation of reports from international1–4 and non- governmental organisations,5 and from individuals6 provide statistical data on health-related indices. Of course, these reports have a purpose beyond simply describing the status quo. The distribution of disease between different populations and over time helps to define causal hypotheses, and to quantify the potential for prevention. Data on disease occurrence and outcome are essential to forming health policy, by quantifying health problems, helping to define priorities for preventive and curative programmes, and for evaluation of their outcomes in relation to resource inputs. With respect to cancer, various statistical indices may be used, but the most basic indicators of cancer burden are listed below and data for these indices in 2000 are shown in Figure 1. GIncidence: the number of new cases occurring, expressed as an absolute number of cases per year or as a rate per 100 000 people per year. The latter estimates the average risk of developing cancer, and is used for comparisons between populations (countries, ethnic groups, or different time periods). Primary prevention strategies aim to reduce incidence. G Mortality: death provides an unambiguous measure of the outcome or impact of cancer. It is the product of the incidence and the fatality of a given cancer. Mortality rates therefore measure the average risk to the population of dying from a specific cancer, whereas survival (1-fatality) represents the probability that an individual with cancer will not die from it. Mortality rates are frequently used as a substitute measure of the risk of acquiring the disease (incidence) when comparing different groups, since these data may be more generally available. However, this approach assumes equal survival/fatality in the populations being compared. Since this is rarely correct – there are, for example, quite large differences between countries – mortality is a more appropriate measure of outcome than occurrence. GPrevalence: the number of people alive with the disease of interest at a particular time. There is no clear agreement on what is meant by ‘having’ cancer. Some authors take it to mean ever having been diagnosed with cancer, even if this was many years ago, and the patient is cured. This definition makes little sense. It would be more useful to DMP is at the International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France. Tel: +33 (0)4 72 73 84 82. Fax: +33 (0)4 72 73 86 50. Email: parkin@iarc.fr Correspondence: Dr D Maxwell Parkin, MD, Unit of Descriptive Epidemiology, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France. Reviews Lung Liver Breast Cervix Colon/rectum Prostate Stomach Oesophagus (a) (b) (c) Figure 1. Worldwide data (2000) for cancer in both sexes. (a) Incidence, (b) mortality, and (c) prevalence.
  2. 2. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001534 consider people as ‘alive, with cancer’ if they are still receiving some form of treatment or, at least, being followed up medically for the disease. Such a statistic is not only hard to obtain, but would certainly vary between populations, depending on medical practice. However, since ‘cure’ is often taken to equate with survival beyond 5 years, at least for statistical purposes, a compromise is to estimate prevalence as the number of people alive who have had cancer diagnosed within the last 5 years.7 Other more complex statistics have been used to measure the impact of disease. For instance, person-years of life lost, defined as how many years of normal lifespan are lost due to deaths from cancer. Disability-adjusted; or quality-adjusted life-years lost attempt to give a numerical score to the years lived with a reduced quality of life between diagnosis and death (where quality = 0) or cure (quality = 1). In this article, the relative importance of different cancers worldwide is presented as the absolute numbers of people developing, living with (5-year prevalence), or dying from, cancer in the year 2000. Estimation The global estimates are built up from estimates of incidence, mortality, and prevalence in every nation in the world. The methods used have been described with respect to earlier estimates for 1990.7–9 The basic data are the best available information on incidence, mortality, and survival in a country. Incidence rates are obtained from cancer registries. They may cover entire national populations or selected regions. They also provide statistics on cancer survival, enabling incidence to be estimated from mortality. Mortality data, derived from the registration of deaths, are available for many countries, via the World Health Organization (http://www.dep.iarc.fr/dataava/globocan/who.htm). However, the detail and quality of the data (both the accuracy of the recorded cause of death and the completeness of registration) vary substantially. Two types of correction were applied to adjust for quantified under-recording of deaths, and to redistribute deaths recorded as ‘uterus cancer’ to the specific sites of cervix or corpus uteri. Estimation methods were used when one or more indices were unavailable. For example, national incidence rates were estimated, in order of priority, from: GNational incidence data from good-quality cancer registries GNational mortality data, with estimation of incidence using sets of regression models, specific for site, sex, and age, derived from local cancer-registry data (incidence plus mortality). GLocal (regional) incidence data from one or more regional cancer registries within a country. GFrequency data, when only data on the relative frequency of different cancers (by age and sex) are available. The frequencies are applied to an estimated ‘all sites’ incidence rate, derived from existing cancer registry results. GIf there are no data, the country-specific rates are those of the corresponding region (calculated from the other countries for which estimates could be made). Analogous procedures were followed for mortality, so that, for countries where mortality data were unavailable or known to be of poor quality, they were estimated from incidence, using survival data specific to a country or region. The country-specific incidence and mortality rates were estimated for 24 different types of cancer by sex, for five broad age groups (0–14, 15–44, 45–54, 55–64, and 65 years and over). Age-standardised rates (ASRs) were calculated by use of the weights of the ‘world standard’ population (0.31, 0.43, 0.11, 0.08, and 0.07) in the five age groups. Prevalence was estimated from incidence and survival.7 Population-based survival data were collected from three sources: the USA,10 several European countries,11 and less developed countries.12 A full description of the data used for each country, and the detailed set of estimates, are available on a CD-ROM, GLOBOCAN 2000. This CD-ROM contains computer programs to analyse and present the cancer database.13 The database itself can be downloaded from the Internet (http://www.dep.iarc.fr/globocan/globocan.htm), and this website also includes the most recently available incidence and mortality rates from different countries. The most recent incidence and mortality data available are from 3–10 years ago. These rates are used together with population estimates in 200014 as the best possible estimate of global cancer burden in 2000. Incidence and mortality rates were not projected to 2000, partly because historic patterns are not always a sound basis for future projections of time-trend data. In addition, for most of the world, there are simply insufficient historical data to permit such modelling. It is not easy to predict what effect the use of ‘old’ rates (mainly from 1993–97) will have on the accuracy of the ‘burden’ estimate for 2000. For cancer sites for which rates are generally increasing worldwide (for example, incidence of prostate and breast cancers), there will be an underestimate of new cases, and where there is a global decrease, such as stomach cancer, there will be an overestimate. However, for several sites, trends are in different directions in different world regions, and are likely to have changed direction in the past decade, such as lung, colorectal, and cervical cancers, so the net effect is difficult to guess. The estimates vary in accuracy, depending on the extent and validity of the data available for each country. Thus, for the Nordic countries there are high-quality incidence and mortality statistics available nationally, whereas for several less developed countries there are no available data at all, and the estimate is made from data obtained from neighbouring populations (for instance, Afghanistan, Mozambique, and Ghana). Nevertheless, the method does rely on use of the best available data on cancer incidence and/or mortality at country level, and permits continuous updating of the GLOBOCAN database, as newer data become available. This ‘data-based’ approach is rather different from the modelling method used in other estimates.15–18 Essentially, these use sets of regression models, which predict cause-specific mortality rates of different populations from the corresponding all- cause mortality.19 The constants of the regression equations derive from datasets with different overall mortality rates (often including historic data from more developed countries). Cancer deaths in these regression models are then subdivided into the different cancer types, according to the best available information on relative frequencies. Review Global cancer statistics
  3. 3. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 535 The 2000 estimates We estimate that there were 10.1 million new cases, 6.2 million deaths, and 22 million people living with cancer (within 5 years of diagnosis) in 2000 (Figure 1). These estimates are based on the most recent incidence and mortality data available. The total ‘all cancer’ excludes non-melanoma skin cancers, because of the difficulties of measurement, and consequent lack of data. The 2000 estimate represents an increase of about 22% in incidence and mortality since our last comprehensive estimates in 1990.8,9 The cancer profile varies, depending on whether incidence or mortality is the focus of interest, as shown in Figure 2. In terms of incidence, the most common cancers are those of the lung (12.3%), breast (10.4%) and colon and rectum (9.4%). The most common causes of death due to cancer are cancers of the lung (17.8%), stomach (10.4%) and liver (8.8%). Figure 3 shows the 12 most common cancers for men and women (as number of new cases), in the less and more developed regions of the world. Developed countries comprise those of North America, Europe (including the former USSR), Australia/New Zealand, and Japan; less developed countries are the remainder. Figure 4 shows the most prevalent cancers, in men and women, together with the number of annual new cases at the same site. In terms of prevalence, the most common cancers are breast (17.2%), colorectal (10.6%) and prostate (6.9%). The ratio between prevalence and incidence is an indicator of prognosis; thus breast cancer is the most prevalent cancer in the world, although there are less new cases than for stomach (for women) or lung cancer, for which the outlook is considerably poorer. A summary of global patterns and trends for the eight most common cancers follows. Lung cancer This is the most common cancer in the world, both in terms of incidence (1.2 million new cases or 12.3% of the world total) and mortality (1.1 million deaths or 17.8% of the total); 52% of new cases occur in more developed countries. It is by far the most common cancer of men worldwide with the highest rates observed in North America, Europe (especially eastern Europe), South America, and Australia/New Zealand. Moderately high rates are also seen in parts of eastern Asia. In less developed countries the highest rates are seen in the Middle East, China, the Caribbean, South Africa, Zimbabwe, and the Pacific. In women, incidence rates are lower (overall, the rate is 11.1 per 100 000 in women compared with 34.9 per 100 000 in men). The highest rates are in North America and in northwestern Europe, with moderate rates in Australia, New Zealand, and China. National incidence rates closely reflect the history of tobacco smoking.20 The proportion of cases of lung cancer caused by tobacco smoking has been estimated by comparing observed incidence in different areas with incidence rates in non-smokers from several large cohort studies.21 In 1990, 86% of cases in men and 49% in women were estimated to be caused by smoking, although there was much regional variation. Thus, in countries and regions with a long history of smoking, about 90% of cases in men are related to tobacco, whereas the fraction is much lower in Africa and southern Asia. The proportions are more variable in women, even in Europe where they range from 80% in UK to virtually nil in Spain and Portugal, where incidence rates are the same as in non-smoking women in the USA and Japan. Trends in lung-cancer incidence and mortality reflect the maturity of the smoking epidemic in different countries.22,23 Our estimate of the numbers of cases worldwide has increased by 20% since 1990 (17% in men and 27% in women). This overall upward trend disguises substantial differences between countries. In men, several populations have now passed the peak of the tobacco-related epidemic, and incidence and mortality rates are now decreasing, such as in the USA and the countries of northern and western Europe. In contrast, incidence and mortality rates are increasing rapidly in southern and eastern European ReviewGlobal cancer statistics Lung Breast Colon/Rectum Stomach Liver Prostate Cervix uteri Oesophagus Bladder Non-Hodgkin lymphoma Leukaemia Oral cavity Pancreas Kidney Ovary 1000 800 600 400 200 0 200 400 600 800 1000 Men 5.3 million cases 4.7 million deaths Women 4.7 million cases 2.7 million deaths (Thousands) Incidence Mortality 337 293 1050 370 234 446 318 241 165 166 471 233 133 111 76 33 121 68 113 86 47 97 101 101 34 71 192 114 810 902 499 255 405 558 398 384 204 543 279 260 227 99 93 167 144 109 81 170 116 112 57 119 Figure 2. Estimated numbers of new cases (incidence) and deaths (mortality), by sex and site.
  4. 4. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001536 Review Global cancer statistics Breast Lung Colon/Rectum Stomach Prostate Cervix uteri Oesophagus Bladder Non-Hodgkin lymphoma Non-Hodgkin lymphoma Leukaemia Oral cavity Pancreas Kidney Ovary Liver Larynx Lung Colon/Rectum Stomach Oesophagus Leukaemia Liver 600 500 400 300 200 100 0 100 200 300 400 500 600 More developed Less developed Less developed Men (Thousands) (Thousands) 79 62 58 60 39 80 86 110 86 96 224 325 180 127 350 430471 208 416 319 73 55 164 80 Corpus uteri 600 500 400 300 200 100 0 100 200 300 400 500 600 More developed Women 39 55 132 75 101 142 193 154 379 471 117 65 61 66 34 114 91 175 125 292 91 579 16 47 2 176 000 2 562 000Total 2 504 000 2 814 000Total Figure 3. Estimated numbers of new cases in more developed and less developed countries. The 12 most common cancers in each sex are shown.
  5. 5. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 537 countries. In women, the ‘epidemic’ is less advanced; most western countries show a rising trend in incidence and mortality, and in many less developed countries (where smoking in women is generally rare), there is little change in risk. A few countries, where prevalence of smoking in women is declining, already show decreasing rates in younger women. Breast cancer This is the second most frequent cancer in the world (1.05 million cases), and is by far the most common malignant disease in women (22% of all new cancer cases). Worldwide, the ratio of mortality to incidence is about 36%. Because of this relatively favourable prognosis, breast cancer ranks fifth as a cause of death from cancer overall (although it is the leading cause of cancer mortality in women – the 370 000 annual deaths represent 13.9% of cancer deaths in women). Breast cancer is the most prevalent cancer in the world today; there are an estimated 3.9 million women alive who have had breast cancer diagnosed within the past 5 years (compared with just 1.4 million survivors – men or women – from lung cancer). Incidence rates are high in all more developed countries except Japan, with the highest age-standardised incidence in the Netherlands (91.6 per 100 000) and the USA (91.4 per 100 000) (Figure 5). High rates are also observed in southern South America, especially in Uruguay and Argentina. In contrast, most African and Asian populations have low rates of breast cancer, although these are increasing. In some Asian populations rates are already the same as in southern Europe, and in some cases, such as the Philippines, rates are even higher. Prevalence of carriers of the major susceptibility genes (BRCA1 and BRCA2) in the general population is low and the variation observed between populations can explain only some of the observed international and interethnic variation in incidence. Most breast cancer is due to environment and lifestyle factors, as illustrated by the striking changes in risk that follow migration; for example, a rise in risk of breast cancer occurs in migrants to Australia from European countries at relatively low risk (Italy, Poland), particularly when migration takes place in childhood.24,25 Studies comparing the risks in migrants and their offspring, particularly among Asians migrating to the USA, show major increases in risk between first, second, and third generations.26 Incidence rates of breast cancer are increasing in most countries, and the changes are usually greatest where rates were previously low. Since our previous estimates for 1990, there has been an overall increase in incidence rates of about 1.5% annually. However, many low-risk countries are recording increases much greater than this: 2% annually in Japan, for example, and cancer registries in China are recording annual increases in incidence of 3–5%. Trends in mortality from breast cancer are less straightforward, and in many countries there is evidence of a decrease in death rates in recent years. This was first remarked on in the USA,27 but it is also evident in Canada and in some European countries, eg the UK, Netherlands, Denmark, and Norway.28 These changes probably reflect improvements in treatment (and therefore, improved survival), as well as earlier diagnosis, due to both screening programmes and to better awareness of breast cancer and the early signs of the disease in women.29 Colorectal cancers These cancers rank third in frequency of incidence (945 000 new cases, 9.4% of the world total) and mortality (492 000 deaths, 7.9% of the total), with similar numbers in men and women (ratio 1.1 to 1). The relatively good prognosis means that colorectal cancer is the second most prevalent cancer in the world after breast cancer, with an estimated 2.4 million people alive with the disease diagnosed in the previous 5 years (Figure 4). The incidence of large-bowel cancer is high in North America, western Europe, Australia/New Zealand, and southern South America, and low in Africa and Asia. The geographic distribution of colon cancer and rectal cancer is similar, although the variation between countries is less for rectum than for colon. Thus, in high-risk populations, the ReviewGlobal cancer statistics Lung Breast Colon/Rectum Stomach Prostate Cervix uteri Corpus uteri Bladder Non-Hodgkin lymphoma Oral cavity 4000 3000 2000 1000 0 1000 2000 3000 4000 (Thousands) Prevalence Incidence 3860 1050 446 1134 1401 471 496 318 381 291 121 97 256 189 716 76 221 337 1245 449 543 558 902 260 1555 902 1013 779 451 381 170 167 Men Women Figure 4. Estimated numbers of new cases (incidence) and prevalent cases (alive within 5 years of diagnosis), by sex, and site.
  6. 6. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001538 ratio of colon to rectum is 2 to 1 or more (rather more in women), in low-risk countries, rates are similar and there is even a slight excess of rectal cancer in India). These large geographic differences probably represent the effects of different environmental exposures, presumably mainly dietary. It has long been evident from migrant studies that the risk of colon cancer is quite labile to environmental change.30,31 Now, the rates in US Japanese – at least for colon cancer – exceed those in the white population. Incidence rates have been increasing in countries where they were previously low, whereas in high-risk countries, there has been stabilisation or decrease in incidence, particularly in the younger age groups. For mortality, the pattern is similar, with an increase for countries with a low initial rate (eastern Europe, Japan, and Singapore), small increases or stable rates in countries with moderate rates, and a decrease for high-rate populations (western Europe, North America).32,33 Stomach cancer Stomach cancer is the fourth most frequent cancer, with 876 000 new cases (8.7% of the total) and 647 000 deaths (10.4% of cancer deaths) in 2000. Almost two-thirds of these cases occured in less developed countries. Age-standardised incidence rates are highest in Japan (69.2 per 100 000 in men, 28.6 per 100 000 in women). High rates are also present in both sexes in eastern Asia, eastern Europe, and Central and South America. The rates are low in eastern and northern Africa, North America, and southern Asia. Survival for stomach cancer is moderately good only in Japan (52%), where mass screening by photofluoroscopy has been practised since the 1960s; elsewhere – USA10 , Europe11 , and China12 – it is generally in the range 20–25%. The difference in incidence between countries is assumed to be related to dietary factors, which certainly influence individual risk in epidemiological studies. Their importance is consistent with the descriptive data, and studies of migrants. In 1994, the International Agency for Research on Cancer classified infection with Helicobacter pylori as carcinogenic to human beings,34 although its action is probably indirect, by provoking gastritis, a precursor of gastric atrophy, metaplasia, and dysplasia. On the basis of prospective (cohort) studies, the relative risk conferred by H pylori infection is about 2.5.35 The proportion of the population infected is large in less developed countries (80–90%); in more developed countries, the prevalence is lower (about 50%). With these values, H pylori would account for half of the world total for these cancers (55% in less developed countries, and 42% elsewhere). Dietary and other exogenous factors probably have a synergistic or antagonistic role.36 Incidence and mortality of gastric cancer have been decreasing in most countries. Our estimated incidence rates in 2000 were about 11% lower than those for 1990.8 This decrease may be related to improvements in preservation and storage of foods; it may also represent changes in the prevalence of H pylori by birth cohort, perhaps as a result of reduced transmission in childhood, after improved hygiene and reduction of crowding. In contrast to the overall decreasing trend, there has been an increase in cancers localised to the cardia, and this is evident in several populations.37,38 The reasons for this increase are not known; Review Global cancer statistics Figure 5. Estimated age standardised by world standard incidence rates, by country: breast cancer.
  7. 7. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 539 they parallel the increased prevalence of Barrett’s oesophagus and adenocarcinoma of the lower third of the oesophagus. Liver cancer This is the fifth most important cancer worldwide (564 000 or 5.6% of new cancer cases) but, because of the very poor prognosis, the number of deaths is almost the same (549 000), and it is the third most common cause of death from cancer; 81% of cases occur in the less developed countries (with 54% in China). The highest incidence rates are in western and central Africa (where it accounts for almost a quarter of cancer in men), eastern and southeastern Asia, and in Melanesia. Incidence is low in most developed countries, except for Japan, and a moderately increased incidence in some southern European countries. Most liver cancers are hepatocellular carcinomas. The major risk factors for this type are chronic infection with the hepatitis viruses, hepatitis B and C, both of which increase the risk of liver cancer about 20-fold.39 Because hepatitis B virus is more common, the prevalence of chronic infection worldwide largely explains the patterns of liver cancer. The exception is Japan, where prevalence of infection is low, but where the generations most at risk of liver cancer have a relatively high rate of infection with hepatitis C virus.40 More than 75% of cases worldwide, and 85% of cases in less developed countries, are caused by these two viruses.41 Exposure to aflatoxins is probably also an important contributor to the high incidence of liver cancer in tropical areas of the world, where contamination of food grains with the fungus Aspergillus fumigatus is common. There is a multiplicative interaction between aflatoxin exposure and chronic infection with hepatitis B virus, suggesting that the carcinogenic mechanisms differ. Cholangiocarcinoma, a tumour of the epithelium of the intrahepatic bile ducts, comprises 10–25% of liver cancers in men in Europe and North America, and a much greater proportion in women. The incidence shows little international variation, with rates in men between 0.5 and 2.0 per 100 000, and lower rates in women.42 However, the incidence is much higher in some localised areas, where infection with liver flukes is common, such as northeast Thailand. Prostate cancer With 543 000 new cases, prostate cancer is the sixth most common cancer in the world, and third in importance in men (10.2% of new cancer cases – 16.6% in more developed countries and 4.5% in less developed countries). The prognosis is relatively good, so it is a less prominent cause of mortality, with 204 000 deaths (5.8% of cancer deaths in men, 3.3% of all cancer deaths). The estimated prevalence in 2000 was 1.6 million. More than any other cancer, this is a malignant disease of the elderly – 78% cases are in men over age 65. Incidence rates are now influenced by the diagnosis of latent cancers by screening of symptom-free individuals, so that where screening is common, incidence may be very high. For example, it is 104 per 100 000 in the USA, where it is now by far the most commonly diagnosed cancer in men, 65–75 per 100 000 in Scandinavia, and 76 per 100 000 in Australia (probably for the same reason). Mortality is affected by survival, and survival is significantly better in high-risk countries (80% in the USA versus 40% in less developed countries), but much of this is a consequence of latent cancer being detected by screening procedures. As a result, mortality rates are probably a better guide to the risk of invasive prostate cancer in different populations. Mortality rates are high in northern and western Europe, Australia/New Zealand, the Caribbean and North and South America, and also in much of sub-Saharan Africa. Mortality rates are low in Asian populations, and in northern Africa. The difference in incidence between China and the USA is about 60-fold and about 18-fold for mortality. Migrants from low-risk countries, such as Japan, to areas of higher risk, such as the USA, show large increases in incidence. Some of this change reflects an elimination of the diagnostic bias influencing the international incidence rates, but it is almost certainly due partly to changes in environment, possibly including diet. Nevertheless, the interethnic variations in incidence observed within countries – such as between whites, blacks, and Asians in the USA – imply that there are important genetic determinants of risk, and that the prevalence of the relevant genes differs between populations. Polymorphisms in genes controlling androgen metabolism seem to provide at least part of the explanation.43 There has been a rapid increase in the incidence of prostate cancer over the past 15 years – about 1.7% annual increase worldwide. A review of international trends in incidence and mortality44 shows the greatest increases in incidence, especially in younger men, in high-risk countries, probably partly because of the effect of increasing detection of latent cancers after transurethral resection of the prostate, and, more recently, by screening for prostate-specific antigen. In the USA, the burden of prevalent latent cancers in the subset of the population reached by opportunistic screening seems exhausted and incidence began to decrease in the USA after 1992.45 Similar trends have been reported in Canada,46 the UK,47 France,48 Australia,49 and the Netherlands,50 although, in general, they are less striking. Since 1992 in white men, and since 1994 in black men, mortality rates have begun to fall in the USA. There is much debate as to whether this is the consequence of screening.51–53 Mortality and incidence in low-risk countries have also increased: 104% in Chinese in Singapore, 84% in Miyagi, Japan, 55% in Hong Kong, and 44% in Shanghai, China, between 1975 and 1990.43 Although some of this change may relate to better detection and diagnosis, much of it probably relates to westernisation of lifestyles, with increasing obesity and changes in diet, ie increased consumption of meat and fat. Cervical cancer This is the second most common cancer in women worldwide (471 000 annual cases, 233 000 deaths). Almost 80% cases occur in less developed countries, where cervical cancer accounts for 15% of cancer in women, with a lifetime risk of about 2%. In more developed countries it accounts for only 4.2% of new cancers, with a lifetime risk of 1%. The highest incidence rates are observed in Latin America and the ReviewGlobal cancer statistics
  8. 8. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001540 Caribbean, sub-Saharan Africa, and south and southeast Asia (Figure 6). In more developed countries, incidence rates are generally low, probably because of screening, with age- standardised rates less than 14 per 100 000. Very low rates are also observed in China and in western Asia. Human papillomavirus (HPV) is now accepted to be the most important cause of cervical cancer.54 Case-control studies suggest a very high risk associated with viral presence in middle age. With sensitive detection techniques, HPV is found in virtually all cervical cancers, and might, therefore, be considered a necessary cause.55 Recent data from population surveys suggest that there is a correlation between prevalence of HPV infection in the female population and incidence of cervical cancer.56 Other cofactors, such as parity and contraceptives, probably modify the risk in women infected with HPV. Incidence and mortality in cervical cancer have decreased quite substantially, particularly in more developed countries, where there are long-standing screening programmes. Decreases are also seen in some less developed countries, particularly in China where the estimated age-standardised incidence rate in 2000 was 5.2, compared with an estimated 17.8 in 1985.57 Although some of the differences reflect changing data sources, cancer-registry results also indicate a fairly dramatic decrease in rates in recent years.58 As a result of these trends, cervical cancer has ceded its place as the leading cancer in less developed countries to breast cancer, and only in sub-Saharan Africa, Central America, south-central Asia, and Melanesia is it now the main cancer of women. Oesophageal cancer This is the eighth most common cancer worldwide, causing 412 000 new cases (4.1% of the total), and 338 000 deaths. Geographical variation in incidence is very striking. The highest risk areas of the world are in the Asian ‘oesophageal cancer belt’ (stretching from northern Iran through the central Asian republics to north-central China), with incidence rates as high as 200 per 100 000. High rates are also present in parts of east and southeast Africa, eastern South America, and certain parts of western Europe (especially France and Switzerland). For women, the pattern is much the same, with the Indian subcontinent added to the high- ranking areas. Oesophageal cancer is more common in men than in women in most areas – the sex ratio is 6.5 in France for example, although in the high-risk areas of Asia and Africa the sex ratio is much closer to unity. There are also striking variations in incidence within countries in the high-risk areas. These represent exposures to important carcinogens, but it seems that these are quite different in the various high-risk areas.49 Tobacco and alcohol are the main agents involved in Europe and North America, where over 90% of cases can be attributed to these causes. Chewing tobacco and betel are important carcinogens in the Indian subcontinent. Hot beverages have been shown to increase risk, and drinking hot maté is probably the cause of raised rates in Uruguay, southern Brazil, and northern Argentina. Nutritional deficiencies (specifically of micronutrients) are thought to underlie the high risk in central Asia, China, and southern Africa. Here other factors Review Global cancer statistics Figure 6. Estimated age standardised by world standard incidence rates, by country: cancer of the cervix uteri.
  9. 9. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 541 such as pickled vegetables, nitrosamine-rich foods, and mycotoxins may also be involved, as well as consumption of opium residues (in Iran) or pipe-stem residues (in the Transkei of southern Africa). The future Future cancer burden can be projected from trends of incidence and mortality in the past. Our estimates for 2000 did not incorporate any assumptions about existing trends. Prediction of future patterns is even more difficult. For one thing, projections based on historical patterns are not always a sound basis for future predictions. There can be quite abrupt changes in trends in incidence and/or mortality with the development of successful early detection or new forms of treatment, as described above for cancers of the prostate, breast, and cervix. It is hard to foresee what further changes of this type will occur in the next decade, let alone in the next 50 years. Even preparing projections on a world scale is difficult. Past trends varied widely in different world regions, and in many cases the trends have been in opposite directions in different age groups (or birth cohorts) within the past decade, such as lung cancer or colorectal cancers. For much of the world, we do not have enough information on the evolution of age-specific incidence and mortality to make a comprehensive set of projections. On the other hand, it is easy to predict the effects of demographic change – population growth and ageing – on cancer burden in the next few decades. This is because cancer affects the older age groups, and prediction of the numbers of people in these age groups in the next few decades is quite straightforward, since it demands no assumptions about future fertility patterns. In 2000, the world population was estimated at around 6 billion, and, with a projected increase of nearly 80 million people a year, it will reach about 7.5 billion by 2020, and 8.9 billion by 2050.14 Growth rates are much lower in more developed countries than in less developed countries, and will be negative in most by the middle of next century. As a result, population size will peak in more developed countries in about 2020 and then decrease – by 2050 the overall population should be about 2% lower than the 2000 estimate, and the percentage of the world population living in Europe and Northern America is projected to decrease from 17% to 11.5% during this period. In contrast, a 63% increase in the population of the less developed countries is expected between 2000 and 2050. The expansion is particularly evident in Africa – the population is forecast to double by 2030. The rapid increase in the absolute and relative numbers of elderly people was one of the principal characteristics of the world population in the 20th century, because of increasing life expectancy. In less developed countries, for example, life expectancy was 41 years in the mid-1950s, and 64 years by 2000; by 2020 it is forecast to be about 71 years. As a result, the proportion of people over age 65 in less developed regions is projected to increase from 5% in 2000 to 15% in 2050. In more developed areas, the proportion of elderly people in 2000 (14%) is forecast to rise to over 25% by 2050. The impact of population increase and ageing in the next half century can be illustrated by applying the current estimated incidence rates to the population projections specific for age and sex in 2010, 2020, and 2050. Table 1 shows the predicted number of new cases of cancer in the major world regions at these dates. With current rates, the 10.1 million cases in 2000 will increase by 25% in each of the two decades that follow, and by 2050, the number of new cancers will be nearly 24 million. The number of cancer deaths will also rise, from 6.2 million in 2000, to 10 million by 2020, and to 16 million in 2050. In 2000 there were slightly more new cancer cases (53%) and deaths (57%) occurring in less developed than in more developed countries. Since the biggest changes in the demography of the world in the next 50 years will take place in less developed areas, more and more of the future cancer burden will be in these regions. By 2020, population projections suggest that some 9 million new cases will occur in less developed countries compared with 6 million in more developed regions; by 2050, the burden will be over 17 million and 7 million new cases in less and more developed areas, respectively. Population ageing means that an increasing proportion of cancers will develop in the elderly in both more and less developed areas. In 2000, 46% of cancers occurred in people aged 65 or over (57% cases in more developed countries and 42% in less developed countries). This can be projected to rise to 57% of all cancers occurring in the elderly in 2050 (71% in more developed countries, and 53% in less developed countries). These figures are based on current incidence and mortality rates. Clearly, these will not be maintained in the future; incidence and mortality rates of the major cancers are constantly evolving, as described earlier. It is fairly certain ReviewGlobal cancer statistics Table 1. Estimated (2000) and projected numbers of cancer cases The number of new cases (millions) of all cancers Region 2000 2010 2020 2050 World 10.06 12.34 15.35 23.83 More developed regions 4.68 5.31 6.03 6.79 Less developed regions 5.38 7.03 9.32 17.04 Africa 0.3 0.79 1.04 2.53 Asia (Japan) 0.52 0.61 0.67 0.65 Asia (other) 3.94 5.17 6.75 10.74 Europe 2.77 3.06 3.36 3.64 South America 0.83 1.10 1.48 28.81 North America 1.38 1.65 2.03 2.61 Oceania 0.11 0.13 0.16 0.24 Search strategy and selection criteria The data published in this review are the work of the author, and the published articles explaining the methods have been cited. Previous work on global estimates of disease published since 1985 were identified in PubMed. Selected English-language articles from my personal collection were used to explain observed patterns and time trends in the results.
  10. 10. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001542 that stomach cancer rates will continue to decrease, whereas the increasing risk of prostate and breast cancer is likely to be maintained for some time. The decrease in lung cancer finally being achieved in some countries will be offset by the current increases in some countries of eastern Europe and, quite probably, by future increases in many less developed countries. Nevertheless, these simple projections illustrate the increasing toll that cancer will take in our ageing world populations, and highlight the need to seek and apply effective preventive measure, as well as to strive for continued improvements in the effectiveness of treatment. References 1 United Nations Development Programme (UNDP). Human development report 2000. Oxford: Oxford University Press, 2000. 2 United Nations Environment Programme. Global environment outlook 1997. New York: Oxford University Press, 1997. 3 World Health Organisation. World Health Report 2000. WHO, Geneva, 2000. 4 The World Bank. World Development Report 1993. Investing in health. New York: Oxford University Press, 1993. 5 Brown L, French H, Flavin C, et al, Eds. State of the world 2000. The Worldwatch Institute, New York: WW Norton, 2001. 6 Mackay J. The state of health atlas. London: Simon and Schuster, 1993. 7 Pisani F, Bray F, Parkin DM. Estimates of worldwide prevalence of cancer for twenty five sites in the adult population. Int J Cancer (in press). 8 Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of twenty-five major cancers in 1990. Int J Cancer 1999; 80: 827–41. 9 Pisani P, Parkin DM, Bray FI, Ferlay J. Estimates of the worldwide mortality from twenty-five major cancers in 1990: implications for prevention, and projections of future burden. Int J Cancer 1999; 83: 18–29. 10 Ries LA, Kosary CL, Hankey BF, et al, Eds. SEER cancer statistics review 1973–1994. NIH Publication No 97–2789, Bethesda: US Department of Health and Human Services, NCI, 1997. 11 Berrino F, Capocaccia R Est’ve J, Gatta J, et al, Eds. Survival of cancer patients in Europe: the EUROCARE-2 study. IARC Scientific Publication No. 151, Lyon: IARC Press, 1999. 12 Sankaranarayanan R, Black RJ, Parkin DM. Cancer survival in developing countries, IARC Scientific Publication No 145, Lyon: IARC Press, 1998. 13 Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. IARC CancerBase No 5. Lyon: IARC Press, 2001. 14 United Nations. World Population Prospects: the 1998 revision. Volume 1 comprehensive tables, New York: United Nations, 1999. 15 Hakulinen T, Hansluwka, Lopez AD, Nakada T. Global and regional mortality patterns by cause of death in 1980. Int J Epidemiol 1986; 15: 227–33. 16 Bulatao RA, Stevens PW. Estimates and projections of mortality by cause: a global overview, 1970–2015. In: Jamieson DT, Mosley WH, Eds. Evolving health sector priorities in developing countries. Washington: Population, Health and Nutrition Division, The World Bank, 1989. 17 Murray CJL, Lopez A. The global burden of disease. Cambridge: Harvard University Press, 1996. 18 Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 1997; 349: 1436–42. 19 Preston HS. Mortality patterns in national populations. New York: Academic Press, 1976. 20 Doll R, Peto R. The causes of cancer. Oxford: Oxford University Press, 1981. 21 Parkin DM, Pisani P, Lopez AD, Masuyer E. At least one in seven cases of cancer is caused by smoking. Global estimates for 1985. Int J Cancer 1994; 59: 494–504. 22 Gilliland FD, Samet JM. Lung cancer. Cancer Surv 1994; 19–20: 175–95. 23 Lopez-Abente G, Pollan M, de-la Iglesia P, Ruiz M. Characterization of the lung cancer epidemic in the European Union (1970–1990). Cancer Epidemiol Biomarkers Prev 1995; 4: 813–20. Review Global cancer statistics 24 Geddes M, Parkin DM, Khlat M, Balzi D, Buiatti E, Eds. Cancer in Italian migrants populations. IARC Scientific Publication No 123. Lyon: IARC Press, 1993. 25 Tyczynski J, Tarkowski W, Parkin DM, Zatonski W. Cancer mortality among Polish migrants to Australia. Eur J Cancer 1994; 30A, 478–84. 26 Ziegler RG, Hoover RN, Pike MC, et al. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 1993; 85: 1819–27. 27 Blot WJ, Fraumeni JF. Trends in esophageal cancer mortality among US blacks and whites. Am J Public Health 1987; 77: 296–98. 28 Hermon G, Beral V. Breast cancer mortality rates are levelling off or beginning to decrease in many western countries: analysis of time trends, age – cohort and age – period models of breast cancer mortality in 20 countries. Br J Cancer 1996; 73: 955–60. 29 Blanks RG, Moss SM, McGahan CE, et al. Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990–1998: comparison of observed with predicted mortality. BMJ 2000; 321: 665–69. 30 Haenszel W, Kurihara M. Studies of Japanese migrants. I Mortality from cancer and other diseases among Japanese in the United States. J Natl Cancer Inst 1968; 40: 43–68. 31 McMichael AJ, McCall MG, Hartshorne JM, Woodings TL. Patterns of gastrointestinal cancer in European migrants to Australia: the role of dietary change. Int J Cancer 1980; 5: 431–37. 32 McMichael AJ, Giles GG. Colorectal cancer. Cancer Surv 1994; 1920 77–98. 33 Koo LC, Mang OWK, Ho JHC. An ecological study of trends in cancer incidence and dietetary changes in Hong Kong. Nutr Cancer 1997; 28: 289–301. 34 IARC Monograph on the evaluation of carcinogenic risks to humans, Vol 61. Schistosomes, liver flukes and Helicobacter pylori. Lyon: IARC Press, 1994. 35 Danesh J. Helicobacter pylori infection and gastric cancer: systematic review of the epidemiological studies. Aliment Pharmacol Ther 1999; 13: 851–56. 36 World Cancer Research Fund (WCRF) Panel. Diet, nutrition and the prevention of cancer: a global perspective. Washington: World Cancer Research Fund, 1997. 37 Devesa SS, Blot WJ, Fraumeni JF. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83: 2049–53. 38 Laheij RJ, Straatman H, Verbeek AL, Jansen JB. Mortality trend from cancer of the gastric cardia in The Netherlands, 1969–94. Int J Epidemiol 1999; 28: 391–95. 39 Donato F, Boffetta P, Puoti M A. Meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer 1998; 75: 347–54. 40 Tanaka H, Hiyama T, Tsukuma H, et al. Prevalence of second generation antibody to hepatitis C antibody among voluntary blood donors in Osaka, Japan. Cancer Causes Control 1994; 5: 409–13. 41 Parkin DM, Pisani P, Munoz N, Ferlay J. The global health burden of infection associated cancers. In: Weiss RA, Beral V, Newton R, Eds. Infections and human cancer. Vol 33 Cancer Surveys, 1999. 42 Parkin DM, Ohshima H, Srivatanakul P, Vatanasapt V. Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention. Cancer Epidemiol Biomarkers Prev 1993; 2: 537–44. 43 Shibata A, Whittemore A. Genetic predisposition to prostate cancer: possible explanations for ethnic differences in risk. Prostate 1997; 32: 65–72. 44 Hsing AW, Tsao L, Devesa SS. International trends and patterns of prostate cancer incidence and mortality. Int J Cancer 2000; 85: 60–67. 45 Legler JM, Feuer EJ, Potosky AL, et al. The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence decline in the United States. Cancer Causes Control 1998; 9: 519–27. 46 Mercer SL, Goel V, Levy IG, et al. Prostate cancer screening in the midst of controversy: Canadian men’s knowledge, beliefs, utilization, and future intentions. Can J Public Health 1997; 88: 327–32. 47 Chamberlain J, Melia J, Moss S, Brown J. The diagnosis, management, treatment and costs of prostate cancer in England and Wales. Health Technol Assess 1997; 1: 1–53. 48 Grosclaude P, Menegoz F, Schaffer P, et al. Prostate cancer screening (II): is prostate cancer a public health problem? Update of incidence and mortality figures in France from 1982 to 1990. Prog Urol 1997; 7: 647–54.
  11. 11. For personal use. Only reproduce with permission from The Lancet Publishing Group. THE LANCET Oncology Vol 2 September 2001 543 49 Threlfall TJ, English DR, Rouse IL. Prostate cancer in Western Australia: trends in incidence and mortality from 1985 to 1996. Med J Aust 1998; 169: 21–24. 50 Post PN, Kil PJ, Crommelin MA, et al. Trends in incidence and mortality rates for prostate cancer before and after prostate-specific antigen introduction. A registry-based study in southeastern Netherlands, 1971–95. Eur J Cancer 1998; 34: 705–09. 51 Hankey BF, Feuer EJ, Clegg LX, et al. Cancer surveillance series: interpreting trends in prostate cancer-part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J Natl Cancer Inst 1999; 91: 1017–24. 52 Feuer EJ, Merrill RM, Hankey BF. Cancer surveillance series: interpreting trends in prostate cancer, part II: cause of death misclassification and the recent rise and fall in prostate cancer mortality. J Natl Cancer Inst 1999; 91: 1025–32. 53 Etzioni R, Legler JM, Feuer EJ, et al. Cancer surveillance series: interpreting trends in prostate cancer, part III: quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality. J Natl Cancer Inst 1999; 91: 1033–39. 54 IARC Monographs on the evaluation of carcinogenic risks to humans. Volume 64, human papillomavirus. IARC, Lyon, France (1995). 55 Walboomers JMM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 39–43. 56 Herrero R, Munoz N, Lazcano E, et al. HPV international prevalence surveys in general populations. 18th International Papillomavisus Conference, Barcelona, 2000: (abstr 054). 57 Parkin DM, Pisani P, Ferlay J. Estimates of worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993; 54: 594–606. 58 Jin F, Devesa SS, Chow WH, et al. Cancer incidence trends in urban Shanghai, 1972–94: an update. Int J Cancer 1999; 83: 435–40. 59 Munoz N, Day N. Esophageal Cancer. In: Schottenfeld D, Fraumeni JF. Cancer epidemiology and prevention (2nd ed). Oxford University Press, New York, USA (1996). ReviewGlobal cancer statistics Clinical picture Hepatocellular carcinoma and lymphoma – two hepatitis B virus- related malignant diseases? In 1994, a 65-year-old man presented with vague abdominal discomfort and a right hepatic mass measuring 12 x 8 cm, identified by ultrasound. He was positive for hepatitis B surface antigen (HBsAg) with an ␣ fetoprotein (AFP) concentration of 9490 ng/mL (normal < 10 ng/mL). He had a right hepatectomy and the lesion was histologically identified as a well- encapsulated hepatocellular carc- inoma (HCC) with a clear resection margin. The surrounding tissue was non-cirrhotic but there was evidence of chronic persistent hepatitis. He remained well for 6 years, but in October 2000 he presented with a rapidly enlarging and painful left buttock mass (see insert), which had limited his mobility. The AFP concentration was 3 ng/mL. An abdominal and pelvic CT scan (main image) showed evidence of hepatic cirrhosis with no evidence of recurrent HCC. However, there was para-aortic lymphadenopathy of 11 x 9 cm (Y on main image) that extended to the left renal pelvis. Pelvic lymphadenopathy extended directly through the sciatic notch into the left gluteal mass (X on main image) and measured 15 x 12 cm with evidence of destruction of the bony pelvis. Options for diagnosis of the left gluteal mass included lymphoma, pelvic sarcoma with metastases to lymph nodes and kidney, or an unusual extrahepatic recurrance of his HCC, but in view of the long disease-free interval from his initial diagnosis of HCC this was unlikely. Biopsy was required to confirm the diagnosis. Using USG-guided biopsy, the left gluteal mass was identified as a diffuse large B-cell non-Hodgkin lymphoma. The patient was treated with a combination of doxorubicin, vincristine, cyclophosphamide, and prednisolone, and achieved a good partial response after 6 cycles of chemotherapy. Lymphoma are not generally associated with HBV infection, but in this patient, the possibility that this virus had a causative role in the pathogenesis of lymphoma and HCC cannot be ruled out. Winnie Yeo, Pun Hui, John HS Chow, and Tony SK Mok WY, PH, and TSKM are at the Department of Clinical Oncology, and JHSC is at the Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. Correspondence: Dr Winnie Yeo. Email: winnieyeo@cuhk.edu.hk