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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 year2000

D Maxwell Parkin

Estimation of the burden of cancer in terms ofincidence, mortality, and prevalence is a first step toappreciating appropriate control measures in a globalcontext. The latest results of such an exercise, based onthe most recent available international data, show thatthere were 10 million new cases, 6 million deaths, and22 million people living with cancer in 2000. The mostcommon cancers in terms of new cases were lung (1.2million), breast (1.05 million), colorectal (945 000),stomach (876 000), and liver (564 000). The profilevaries greatly in different populations, and theevidence suggests that this variation is mainly aconsequence of different lifestyle and environmentalfactors, which should be amenable to preventiveinterventions. World population growth and ageingimply a progressive increase in the cancer burden – 15million new cases and 10 million new deaths areexpected in 2020, even if current rates remainunchanged.Lancet Oncol 2001; 2: 533–43

Globalisation implies more than the application of marketcapitalism 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 providestatistical data on health-related indices. Of course, thesereports have a purpose beyond simply describing the statusquo. The distribution of disease between differentpopulations and over time helps to define causal hypotheses,and to quantify the potential for prevention. Data on diseaseoccurrence and outcome are essential to forming healthpolicy, by quantifying health problems, helping to definepriorities for preventive and curative programmes, and forevaluation of their outcomes in relation to resource inputs.

With respect to cancer, various statistical indices may beused, but the most basic indicators of cancer burden are listed below and data for these indices in 2000 are shown in Figure 1.�Incidence: the number of new cases occurring, expressed as

an absolute number of cases per year or as a rate per 100 000people per year. The latter estimates the average risk ofdeveloping cancer, and is used for comparisons betweenpopulations (countries, ethnic groups, or different timeperiods). Primary prevention strategies aim to reduceincidence.

� Mortality: death provides an unambiguous measure of theoutcome or impact of cancer. It is the product of theincidence and the fatality of a given cancer. Mortality ratestherefore measure the average risk to the population of

dying from a specific cancer, whereas survival (1-fatality)represents the probability that an individual with cancerwill not die from it. Mortality rates are frequently used as asubstitute measure of the risk of acquiring the disease(incidence) when comparing different groups, since thesedata may be more generally available. However, thisapproach assumes equal survival/fatality in the populationsbeing compared. Since this is rarely correct – there are, forexample, quite large differences between countries –mortality is a more appropriate measure of outcome thanoccurrence.

�Prevalence: the number of people alive with the disease ofinterest at a particular time. There is no clear agreement onwhat is meant by ‘having’ cancer. Some authors take it tomean ever having been diagnosed with cancer, even if thiswas many years ago, and the patient is cured. Thisdefinition makes little sense. It would be more useful to

DMP is at the International Agency for Research on Cancer, 150cours Albert Thomas, 69372 Lyon, France. Tel: +33 (0)4 72 73 8482. Fax: +33 (0)4 72 73 86 50. Email: [email protected]

Correspondence: Dr D Maxwell Parkin, MD, Unit of DescriptiveEpidemiology, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon, France.

Reviews

LungLiver

BreastCervix

Colon/rectumProstate

StomachOesophagus

(a) (b)

(c)

Figure 1. Worldwide data (2000) for cancer in both sexes. (a) Incidence,(b) mortality, and (c) prevalence.


THE LANCET Oncology Vol 2 September 2001534

consider people as ‘alive, with cancer’ if they are stillreceiving some form of treatment or, at least, beingfollowed up medically for the disease. Such a statistic is notonly hard to obtain, but would certainly vary betweenpopulations, depending on medical practice. However,since ‘cure’ is often taken to equate with survival beyond 5years, at least for statistical purposes, a compromise is toestimate prevalence as the number of people alive who havehad cancer diagnosed within the last 5 years.7

Other more complex statistics have been used to measurethe impact of disease. For instance, person-years of life lost,defined as how many years of normal lifespan are lost due todeaths from cancer. Disability-adjusted; or quality-adjustedlife-years lost attempt to give a numerical score to the yearslived with a reduced quality of life between diagnosis anddeath (where quality = 0) or cure (quality = 1).

In this article, the relative importance of different cancersworldwide is presented as the absolute numbers of peopledeveloping, living with (5-year prevalence), or dying from,cancer in the year 2000.

EstimationThe global estimates are built up from estimates of incidence,mortality, and prevalence in every nation in the world. Themethods used have been described with respect to earlierestimates for 1990.7–9 The basic data are the best availableinformation on incidence, mortality, and survival in acountry. Incidence rates are obtained from cancer registries.They may cover entire national populations or selectedregions. They also provide statistics on cancer survival,enabling incidence to be estimated from mortality. Mortalitydata, derived from the registration of deaths, are available formany countries, via the World Health Organization(http://www.dep.iarc.fr/dataava/globocan/who.htm).However, the detail and quality of the data (both theaccuracy of the recorded cause of death and the completenessof registration) vary substantially. Two types of correctionwere applied to adjust for quantified under-recording ofdeaths, and to redistribute deaths recorded as ‘uterus cancer’to the specific sites of cervix or corpus uteri. Estimationmethods were used when one or more indices wereunavailable. For example, national incidence rates wereestimated, in order of priority, from:�National incidence data from good-quality cancer registries �National mortality data, with estimation of incidence using

sets of regression models, specific for site, sex, and age,derived from local cancer-registry data (incidence plusmortality).

�Local (regional) incidence data from one or more regionalcancer registries within a country.

�Frequency data, when only data on the relative frequency ofdifferent cancers (by age and sex) are available. Thefrequencies are applied to an estimated ‘all sites’ incidencerate, derived from existing cancer registry results.

�If there are no data, the country-specific rates are those ofthe corresponding region (calculated from the othercountries for which estimates could be made).

Analogous procedures were followed for mortality, so that, for countries where mortality data were unavailableor known to be of poor quality, they were estimated

from incidence, using survival data specific to a country orregion.

The country-specific incidence and mortality rates wereestimated for 24 different types of cancer by sex, for fivebroad age groups (0–14, 15–44, 45–54, 55–64, and 65 yearsand over). Age-standardised rates (ASRs) were calculated byuse 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 threesources: the USA,10 several European countries,11 and lessdeveloped countries.12

A full description of the data used for each country, andthe detailed set of estimates, are available on a CD-ROM,GLOBOCAN 2000. This CD-ROM contains computerprograms to analyse and present the cancer database.13 Thedatabase itself can be downloaded from the Internet(http://www.dep.iarc.fr/globocan/globocan.htm), and thiswebsite also includes the most recently available incidenceand mortality rates from different countries. The most recentincidence and mortality data available are from 3–10 yearsago. These rates are used together with population estimatesin 200014 as the best possible estimate of global cancer burdenin 2000. Incidence and mortality rates were not projected to2000, partly because historic patterns are not always a soundbasis for future projections of time-trend data. In addition,for most of the world, there are simply insufficient historicaldata to permit such modelling. It is not easy to predict whateffect the use of ‘old’ rates (mainly from 1993–97) will haveon the accuracy of the ‘burden’ estimate for 2000. For cancersites for which rates are generally increasing worldwide (forexample, incidence of prostate and breast cancers), there willbe an underestimate of new cases, and where there is a globaldecrease, such as stomach cancer, there will be anoverestimate. However, for several sites, trends are indifferent directions in different world regions, and are likelyto have changed direction in the past decade, such as lung,colorectal, and cervical cancers, so the net effect is difficult toguess.

The estimates vary in accuracy, depending on the extentand validity of the data available for each country. Thus, forthe Nordic countries there are high-quality incidence andmortality statistics available nationally, whereas for severalless developed countries there are no available data at all, andthe estimate is made from data obtained from neighbouringpopulations (for instance, Afghanistan, Mozambique, andGhana). Nevertheless, the method does rely on use of the bestavailable data on cancer incidence and/or mortality atcountry level, and permits continuous updating of theGLOBOCAN database, as newer data become available. This‘data-based’ approach is rather different from the modellingmethod used in other estimates.15–18 Essentially, these use setsof regression models, which predict cause-specific mortalityrates of different populations from the corresponding all-cause mortality.19 The constants of the regression equationsderive from datasets with different overall mortality rates(often including historic data from more developedcountries). Cancer deaths in these regression models are thensubdivided into the different cancer types, according to thebest available information on relative frequencies.

Review Global cancer statistics



The 2000 estimatesWe estimate that there were 10.1million new cases, 6.2 million deaths,and 22 million people living withcancer (within 5 years of diagnosis) in2000 (Figure 1). These estimates arebased on the most recent incidence andmortality data available. The total ‘allcancer’ excludes non-melanoma skincancers, because of the difficulties ofmeasurement, and consequent lack ofdata. The 2000 estimate represents anincrease of about 22% in incidence andmortality since our last comprehensiveestimates in 1990.8,9 The cancer profilevaries, depending on whetherincidence or mortality is the focus ofinterest, as shown in Figure 2. In termsof incidence, the most commoncancers are those of the lung (12.3%),breast (10.4%) and colon and rectum(9.4%). The most common causes ofdeath due to cancer are cancers of thelung (17.8%), stomach (10.4%) andliver (8.8%).

Figure 3 shows the 12 mostcommon cancers for men and women(as number of new cases), in the lessand more developed regions of theworld. Developed countries comprisethose of North America, Europe(including the former USSR),Australia/New Zealand, and Japan; less developed countriesare the remainder.

Figure 4 shows the most prevalent cancers, in men andwomen, together with the number of annual new cases at thesame site. In terms of prevalence, the most common cancersare breast (17.2%), colorectal (10.6%) and prostate (6.9%).The ratio between prevalence and incidence is an indicator ofprognosis; thus breast cancer is the most prevalent cancer inthe world, although there are less new cases than for stomach(for women) or lung cancer, for which the outlook isconsiderably poorer.

A summary of global patterns and trends for the eightmost common cancers follows.

Lung cancer This is the most common cancer in the world, both in termsof incidence (1.2 million new cases or 12.3% of the worldtotal) and mortality (1.1 million deaths or 17.8% of thetotal); 52% of new cases occur in more developed countries.It is by far the most common cancer of men worldwide withthe highest rates observed in North America, Europe(especially eastern Europe), South America, andAustralia/New Zealand. Moderately high rates are also seenin parts of eastern Asia. In less developed countries thehighest rates are seen in the Middle East, China, theCaribbean, South Africa, Zimbabwe, and the Pacific. Inwomen, incidence rates are lower (overall, the rate is 11.1 per100 000 in women compared with 34.9 per 100 000 in men).

The highest rates are in North America and in northwesternEurope, with moderate rates in Australia, New Zealand, andChina.

National incidence rates closely reflect the history oftobacco smoking.20 The proportion of cases of lung cancercaused by tobacco smoking has been estimated by comparingobserved incidence in different areas with incidence rates innon-smokers from several large cohort studies.21 In 1990,86% of cases in men and 49% in women were estimated to becaused by smoking, although there was much regionalvariation. Thus, in countries and regions with a long historyof smoking, about 90% of cases in men are related totobacco, whereas the fraction is much lower in Africa andsouthern Asia. The proportions are more variable in women,even in Europe where they range from 80% in UK to virtuallynil in Spain and Portugal, where incidence rates are the sameas in non-smoking women in the USA and Japan.

Trends in lung-cancer incidence and mortality reflect thematurity of the smoking epidemic in different countries.22,23

Our estimate of the numbers of cases worldwide hasincreased by 20% since 1990 (17% in men and 27% inwomen). This overall upward trend disguises substantialdifferences between countries. In men, several populationshave now passed the peak of the tobacco-related epidemic,and incidence and mortality rates are now decreasing, such asin the USA and the countries of northern and westernEurope. In contrast, incidence and mortality rates areincreasing rapidly in southern and eastern European

ReviewGlobal cancer statistics

Lung

Breast

Colon/Rectum

Stomach

Liver

Prostate

Cervix uteri

Oesophagus

Bladder

Non-Hodgkinlymphoma

Leukaemia

Oral cavity

Pancreas

Kidney

Ovary

1000 800 600 400 200 0 200 400 600 800 1000

Men

5.3 million cases4.7 million deaths

Women

4.7 million cases2.7 million deaths

(Thousands)

Incidence

Mortality

337293

1050370

234446

318241

165166

471233

133111

7633

12168

11386

4797

101101

3471

192114

810902

499255

405558

398384

204543

279

260227

99

93167

144109

81170

116112

57119

Figure 2. Estimated numbers of new cases (incidence) and deaths (mortality), by sex and site.




Breast

Lung

Colon/Rectum

Stomach

Prostate

Cervix uteri

Oesophagus

Bladder

Non-Hodgkinlymphoma

Non-Hodgkinlymphoma

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.



countries. In women, the ‘epidemic’ isless advanced; most western countriesshow a rising trend in incidence andmortality, and in many less developedcountries (where smoking in women isgenerally rare), there is little change inrisk. A few countries, where prevalenceof smoking in women is declining,already show decreasing rates inyounger women.

Breast cancerThis is the second most frequentcancer in the world (1.05 millioncases), and is by far the most commonmalignant disease in women (22% ofall new cancer cases). Worldwide, theratio of mortality to incidence is about36%. Because of this relativelyfavourable prognosis, breast cancerranks fifth as a cause of death fromcancer overall (although it is theleading cause of cancer mortality inwomen – the 370 000 annual deathsrepresent 13.9% of cancer deaths inwomen). Breast cancer is the mostprevalent cancer in the world today;there are an estimated 3.9 millionwomen alive who have had breastcancer diagnosed within the past 5years (compared with just 1.4 million survivors – men orwomen – from lung cancer).

Incidence rates are high in all more developed countriesexcept Japan, with the highest age-standardised incidence inthe Netherlands (91.6 per 100 000) and the USA (91.4 per100 000) (Figure 5). High rates are also observed in southernSouth America, especially in Uruguay and Argentina. Incontrast, most African and Asian populations have low ratesof breast cancer, although these are increasing. In some Asianpopulations rates are already the same as in southern Europe,and in some cases, such as the Philippines, rates are evenhigher.

Prevalence of carriers of the major susceptibility genes(BRCA1 and BRCA2) in the general population is low andthe variation observed between populations can explain onlysome of the observed international and interethnic variationin incidence. Most breast cancer is due to environment andlifestyle factors, as illustrated by the striking changes in riskthat follow migration; for example, a rise in risk of breastcancer occurs in migrants to Australia from Europeancountries at relatively low risk (Italy, Poland), particularlywhen migration takes place in childhood.24,25 Studiescomparing the risks in migrants and their offspring,particularly among Asians migrating to the USA, show majorincreases in risk between first, second, and thirdgenerations.26

Incidence rates of breast cancer are increasing in mostcountries, and the changes are usually greatest where rateswere 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 arerecording increases much greater than this: 2% annually inJapan, for example, and cancer registries in China arerecording annual increases in incidence of 3–5%. Trends inmortality from breast cancer are less straightforward, and inmany countries there is evidence of a decrease in death ratesin recent years. This was first remarked on in the USA,27 but itis also evident in Canada and in some European countries, egthe UK, Netherlands, Denmark, and Norway.28 Thesechanges probably reflect improvements in treatment (and therefore, improved survival), as well as earlierdiagnosis, due to both screening programmes and to betterawareness of breast cancer and the early signs of the diseasein women.29

Colorectal cancersThese cancers rank third in frequency of incidence (945 000new cases, 9.4% of the world total) and mortality (492 000deaths, 7.9% of the total), with similar numbers in men andwomen (ratio 1.1 to 1). The relatively good prognosis meansthat colorectal cancer is the second most prevalent cancer inthe world after breast cancer, with an estimated 2.4 millionpeople alive with the disease diagnosed in the previous 5years (Figure 4).

The incidence of large-bowel cancer is high in NorthAmerica, western Europe, Australia/New Zealand, andsouthern South America, and low in Africa and Asia. Thegeographic distribution of colon cancer and rectal cancer issimilar, although the variation between countries is less forrectum than for colon. Thus, in high-risk populations, the


Lung

Breast

Colon/Rectum

Stomach

Prostate

Cervix uteri

Corpus uteri

Bladder

Non-Hodgkinlymphoma

Oral cavity

4000 3000 2000 1000 0 1000 2000 3000 4000(Thousands)

Prevalence

Incidence

38601050

4461134

1401471

496318

381

291121

97256

189716

76221

337

1245449

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 ofdiagnosis), by sex, and site.



ratio of colon to rectum is 2 to 1 or more (rather more inwomen), in low-risk countries, rates are similar and there iseven a slight excess of rectal cancer in India).

These large geographic differences probably represent theeffects of different environmental exposures, presumablymainly dietary. It has long been evident from migrant studiesthat the risk of colon cancer is quite labile to environmentalchange.30,31 Now, the rates in US Japanese – at least for coloncancer – exceed those in the white population.

Incidence rates have been increasing in countries wherethey were previously low, whereas in high-risk countries,there has been stabilisation or decrease in incidence,particularly in the younger age groups. For mortality, thepattern is similar, with an increase for countries with a lowinitial rate (eastern Europe, Japan, and Singapore), smallincreases or stable rates in countries with moderate rates, anda decrease for high-rate populations (western Europe, NorthAmerica).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 thesecases occured in less developed countries. Age-standardisedincidence rates are highest in Japan (69.2 per 100 000 in men,28.6 per 100 000 in women). High rates are also present inboth sexes in eastern Asia, eastern Europe, and Central andSouth America. The rates are low in eastern and northernAfrica, North America, and southern Asia. Survival forstomach cancer is moderately good only in Japan (52%),where mass screening by photofluoroscopy has been

practised since the 1960s; elsewhere – USA10, Europe11, andChina12 – it is generally in the range 20–25%.

The difference in incidence between countries is assumedto be related to dietary factors, which certainly influenceindividual risk in epidemiological studies. Their importanceis consistent with the descriptive data, and studies ofmigrants. In 1994, the International Agency for Research onCancer classified infection with Helicobacter pylori ascarcinogenic to human beings,34 although its action isprobably indirect, by provoking gastritis, a precursor ofgastric atrophy, metaplasia, and dysplasia. On the basis ofprospective (cohort) studies, the relative risk conferred by Hpylori infection is about 2.5.35 The proportion of thepopulation infected is large in less developed countries(80–90%); in more developed countries, the prevalence islower (about 50%). With these values, H pylori wouldaccount for half of the world total for these cancers (55% inless developed countries, and 42% elsewhere). Dietary andother exogenous factors probably have a synergistic orantagonistic role.36

Incidence and mortality of gastric cancer have beendecreasing in most countries. Our estimated incidence ratesin 2000 were about 11% lower than those for 1990.8 Thisdecrease may be related to improvements in preservation andstorage of foods; it may also represent changes in theprevalence of H pylori by birth cohort, perhaps as a result ofreduced transmission in childhood, after improved hygieneand reduction of crowding. In contrast to the overalldecreasing trend, there has been an increase in cancerslocalised to the cardia, and this is evident in severalpopulations.37,38 The reasons for this increase are not known;


Figure 5. Estimated age standardised by world standard incidence rates, by country: breast cancer.



they parallel the increased prevalence of Barrett’s oesophagusand adenocarcinoma of the lower third of the oesophagus.

Liver cancer This is the fifth most important cancer worldwide (564 000or 5.6% of new cancer cases) but, because of the very poorprognosis, the number of deaths is almost the same (549 000), and it is the third most common cause of deathfrom cancer; 81% of cases occur in the less developedcountries (with 54% in China). The highest incidence ratesare in western and central Africa (where it accounts foralmost a quarter of cancer in men), eastern and southeasternAsia, and in Melanesia. Incidence is low in most developedcountries, except for Japan, and a moderately increasedincidence in some southern European countries.

Most liver cancers are hepatocellular carcinomas. Themajor risk factors for this type are chronic infection with thehepatitis viruses, hepatitis B and C, both of which increasethe risk of liver cancer about 20-fold.39 Because hepatitis Bvirus is more common, the prevalence of chronic infectionworldwide largely explains the patterns of liver cancer. Theexception 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% ofcases in less developed countries, are caused by these twoviruses.41

Exposure to aflatoxins is probably also an importantcontributor to the high incidence of liver cancer in tropicalareas of the world, where contamination of food grains withthe fungus Aspergillus fumigatus is common. There is amultiplicative interaction between aflatoxin exposure andchronic infection with hepatitis B virus, suggesting that thecarcinogenic mechanisms differ.

Cholangiocarcinoma, a tumour of the epithelium of theintrahepatic bile ducts, comprises 10–25% of liver cancers inmen in Europe and North America, and a much greaterproportion in women. The incidence shows littleinternational variation, with rates in men between 0.5 and2.0 per 100 000, and lower rates in women.42 However, theincidence is much higher in some localised areas, whereinfection with liver flukes is common, such as northeastThailand.

Prostate cancerWith 543 000 new cases, prostate cancer is the sixth mostcommon cancer in the world, and third in importance inmen (10.2% of new cancer cases – 16.6% in more developedcountries and 4.5% in less developed countries). Theprognosis is relatively good, so it is a less prominent cause ofmortality, with 204 000 deaths (5.8% of cancer deaths inmen, 3.3% of all cancer deaths). The estimated prevalence in2000 was 1.6 million. More than any other cancer, this is amalignant disease of the elderly – 78% cases are in men overage 65.

Incidence rates are now influenced by the diagnosis oflatent cancers by screening of symptom-free individuals, sothat where screening is common, incidence may be very high.For example, it is 104 per 100 000 in the USA, where it is nowby 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 issignificantly better in high-risk countries (80% in the USAversus 40% in less developed countries), but much of this is aconsequence of latent cancer being detected by screeningprocedures. As a result, mortality rates are probably a betterguide to the risk of invasive prostate cancer in differentpopulations. Mortality rates are high in northern and westernEurope, Australia/New Zealand, the Caribbean and Northand South America, and also in much of sub-Saharan Africa.Mortality rates are low in Asian populations, and in northernAfrica. The difference in incidence between China and theUSA is about 60-fold and about 18-fold for mortality.

Migrants from low-risk countries, such as Japan, to areasof higher risk, such as the USA, show large increases inincidence. Some of this change reflects an elimination of thediagnostic bias influencing the international incidence rates,but it is almost certainly due partly to changes inenvironment, possibly including diet. Nevertheless, theinterethnic 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 betweenpopulations. Polymorphisms in genes controlling androgenmetabolism seem to provide at least part of the explanation.43

There has been a rapid increase in the incidence ofprostate cancer over the past 15 years – about 1.7% annualincrease worldwide. A review of international trends inincidence and mortality44 shows the greatest increases inincidence, especially in younger men, in high-risk countries,probably partly because of the effect of increasing detectionof latent cancers after transurethral resection of the prostate,and, more recently, by screening for prostate-specificantigen. In the USA, the burden of prevalent latent cancers inthe subset of the population reached by opportunisticscreening seems exhausted and incidence began to decreasein the USA after 1992.45 Similar trends have been reported inCanada,46 the UK,47 France,48 Australia,49 and theNetherlands,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 muchdebate as to whether this is the consequence of screening.51–53

Mortality and incidence in low-risk countries have alsoincreased: 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 mayrelate to better detection and diagnosis, much of it probablyrelates to westernisation of lifestyles, with increasing obesityand changes in diet, ie increased consumption of meat and fat.

Cervical cancer This is the second most common cancer in womenworldwide (471 000 annual cases, 233 000 deaths). Almost80% cases occur in less developed countries, where cervicalcancer accounts for 15% of cancer in women, with a lifetimerisk of about 2%. In more developed countries it accounts foronly 4.2% of new cancers, with a lifetime risk of 1%. Thehighest incidence rates are observed in Latin America and the




Caribbean, sub-Saharan Africa, and south and southeast Asia(Figure 6). In more developed countries, incidence rates aregenerally low, probably because of screening, with age-standardised rates less than 14 per 100 000. Very low rates arealso observed in China and in western Asia.

Human papillomavirus (HPV) is now accepted to be themost important cause of cervical cancer.54 Case-controlstudies suggest a very high risk associated with viral presencein middle age. With sensitive detection techniques, HPV isfound in virtually all cervical cancers, and might, therefore,be considered a necessary cause.55 Recent data frompopulation surveys suggest that there is a correlation betweenprevalence of HPV infection in the female population andincidence of cervical cancer.56 Other cofactors, such as parityand contraceptives, probably modify the risk in womeninfected with HPV.

Incidence and mortality in cervical cancer have decreasedquite 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-standardisedincidence rate in 2000 was 5.2, compared with an estimated17.8 in 1985.57 Although some of the differences reflectchanging data sources, cancer-registry results also indicate afairly dramatic decrease in rates in recent years.58 As a result ofthese trends, cervical cancer has ceded its place as the leadingcancer in less developed countries to breast cancer, and onlyin 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, causing412 000 new cases (4.1% of the total), and 338 000 deaths.Geographical variation in incidence is very striking. Thehighest risk areas of the world are in the Asian ‘oesophagealcancer belt’ (stretching from northern Iran through thecentral Asian republics to north-central China), withincidence rates as high as 200 per 100 000. High rates are alsopresent in parts of east and southeast Africa, eastern SouthAmerica, and certain parts of western Europe (especiallyFrance and Switzerland). For women, the pattern is much thesame, with the Indian subcontinent added to the high-ranking areas. Oesophageal cancer is more common in menthan in women in most areas – the sex ratio is 6.5 in Francefor example, although in the high-risk areas of Asia andAfrica the sex ratio is much closer to unity.

There are also striking variations in incidence withincountries in the high-risk areas. These represent exposures toimportant carcinogens, but it seems that these are quitedifferent in the various high-risk areas.49 Tobacco and alcoholare 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 theIndian subcontinent. Hot beverages have been shown toincrease risk, and drinking hot maté is probably the cause ofraised rates in Uruguay, southern Brazil, and northernArgentina. Nutritional deficiencies (specifically ofmicronutrients) are thought to underlie the high risk incentral Asia, China, and southern Africa. Here other factors


Figure 6. Estimated age standardised by world standard incidence rates, by country: cancer of the cervix uteri.



such as pickled vegetables, nitrosamine-rich foods, andmycotoxins may also be involved, as well as consumption ofopium residues (in Iran) or pipe-stem residues (in theTranskei of southern Africa).

The futureFuture cancer burden can be projected from trends ofincidence and mortality in the past. Our estimates for 2000did not incorporate any assumptions about existing trends.Prediction of future patterns is even more difficult. For onething, projections based on historical patterns are not alwaysa sound basis for future predictions. There can be quiteabrupt changes in trends in incidence and/or mortality withthe development of successful early detection or new formsof treatment, as described above for cancers of the prostate,breast, and cervix. It is hard to foresee what further changesof this type will occur in the next decade, let alone in the next50 years. Even preparing projections on a world scale isdifficult. Past trends varied widely in different world regions,and in many cases the trends have been in oppositedirections in different age groups (or birth cohorts) withinthe past decade, such as lung cancer or colorectal cancers. Formuch of the world, we do not have enough information onthe evolution of age-specific incidence and mortality to makea comprehensive set of projections.

On the other hand, it is easy to predict the effects ofdemographic change – population growth and ageing – oncancer burden in the next few decades. This is because canceraffects the older age groups, and prediction of the numbers ofpeople in these age groups in the next few decades is quitestraightforward, since it demands no assumptions aboutfuture fertility patterns.

In 2000, the world population was estimated at around 6 billion, and, with a projected increase of nearly 80 millionpeople a year, it will reach about 7.5 billion by 2020, and 8.9 billion by 2050.14 Growth rates are much lower in moredeveloped countries than in less developed countries, andwill be negative in most by the middle of next century. As aresult, population size will peak in more developed countriesin about 2020 and then decrease – by 2050 the overallpopulation should be about 2% lower than the 2000estimate, and the percentage of the world population livingin Europe and Northern America is projected to decreasefrom 17% to 11.5% during this period. In contrast, a 63%increase in the population of the less developed countries isexpected between 2000 and 2050. The expansion isparticularly evident in Africa – the population is forecast todouble by 2030.

The rapid increase in the absolute and relative numbers ofelderly people was one of the principal characteristics of theworld population in the 20th century, because of increasinglife expectancy. In less developed countries, for example, lifeexpectancy was 41 years in the mid-1950s, and 64 years by2000; by 2020 it is forecast to be about 71 years. As a result,the proportion of people over age 65 in less developed regionsis projected to increase from 5% in 2000 to 15% in 2050. Inmore developed areas, the proportion of elderly people in2000 (14%) is forecast to rise to over 25% by 2050.

The impact of population increase and ageing in the nexthalf century can be illustrated by applying the current

estimated incidence rates to the population projectionsspecific for age and sex in 2010, 2020, and 2050. Table 1shows the predicted number of new cases of cancer in themajor world regions at these dates. With current rates, the10.1 million cases in 2000 will increase by 25% in each of thetwo decades that follow, and by 2050, the number of newcancers will be nearly 24 million. The number of cancerdeaths will also rise, from 6.2 million in 2000, to 10 millionby 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 moredeveloped countries. Since the biggest changes in thedemography of the world in the next 50 years will take placein less developed areas, more and more of the future cancerburden will be in these regions. By 2020, populationprojections suggest that some 9 million new cases will occurin less developed countries compared with 6 million in moredeveloped regions; by 2050, the burden will be over 17million and 7 million new cases in less and more developedareas, respectively.

Population ageing means that an increasing proportionof cancers will develop in the elderly in both more and lessdeveloped areas. In 2000, 46% of cancers occurred in peopleaged 65 or over (57% cases in more developed countries and42% in less developed countries). This can be projected torise to 57% of all cancers occurring in the elderly in 2050(71% in more developed countries, and 53% in lessdeveloped countries).

These figures are based on current incidence andmortality rates. Clearly, these will not be maintained in thefuture; incidence and mortality rates of the major cancers areconstantly evolving, as described earlier. It is fairly certain


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 criteriaThe data published in this review are the work of theauthor, and the published articles explaining the methodshave been cited. Previous work on global estimates ofdisease published since 1985 were identified in PubMed.Selected English-language articles from my personalcollection were used to explain observed patterns and timetrends in the results.



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Clinical pictureHepatocellular carcinoma andlymphoma – two hepatitis B virus-related malignant diseases?In 1994, a 65-year-old man presentedwith vague abdominal discomfort anda right hepatic mass measuring 12 x 8cm, identified by ultrasound. He waspositive for hepatitis B surface antigen(HBsAg) with an � fetoprotein (AFP)concentration of 9490 ng/mL (normal< 10 ng/mL). He had a righthepatectomy and the lesion washistologically identified as a well-encapsulated hepatocellular carc-inoma (HCC) with a clear resectionmargin. The surrounding tissue wasnon-cirrhotic but there was evidenceof chronic persistent hepatitis. Heremained well for 6 years, but inOctober 2000 he presented with arapidly enlarging and painful leftbuttock mass (see insert), which had limited his mobility.

The AFP concentration was 3 ng/mL. An abdominal andpelvic CT scan (main image) showed evidence of hepaticcirrhosis with no evidence of recurrent HCC. However,there was para-aortic lymphadenopathy of 11 x 9 cm (Y onmain image) that extended to the left renal pelvis. Pelviclymphadenopathy extended directly through the sciaticnotch into the left gluteal mass (X on main image) andmeasured 15 x 12 cm with evidence of destruction of thebony pelvis. Options for diagnosis of the left gluteal massincluded lymphoma, pelvic sarcoma with metastases tolymph nodes and kidney, or an unusual extrahepaticrecurrance of his HCC, but in view of the long disease-freeinterval from his initial diagnosis of HCC this was unlikely.Biopsy was required to confirm the diagnosis.

Using USG-guided biopsy, the left gluteal mass wasidentified as a diffuse large B-cell non-Hodgkin lymphoma.The patient was treated with a combination of doxorubicin,vincristine, cyclophosphamide, and prednisolone, andachieved a good partial response after 6 cycles ofchemotherapy.

Lymphoma are not generally associated with HBVinfection, but in this patient, the possibility that this virushad a causative role in the pathogenesis of lymphoma andHCC cannot be ruled out.Winnie Yeo, Pun Hui, John HS Chow, and Tony SK MokWY, PH, and TSKM are at the Department of Clinical Oncology, andJHSC 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: [email protected]

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