Trends in oesophageal cancer incidence and mortality in Europe
Article first published online: 7 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 5, pages 1118–1129, 1 March 2008
How to Cite
Bosetti, C., Levi, F., Ferlay, J., Garavello, W., Lucchini, F., Bertuccio, P., Negri, E. and Vecchia, C. L. (2008), Trends in oesophageal cancer incidence and mortality in Europe. Int. J. Cancer, 122: 1118–1129. doi: 10.1002/ijc.23232
- Issue published online: 24 DEC 2007
- Article first published online: 7 NOV 2007
- Manuscript Accepted: 10 SEP 2007
- Manuscript Received: 22 JUN 2007
- Italian and Swiss Leagues Against Cancer
- Swiss Foundation for Research Against Cancer
- Italian Association for Cancer Research
- International Agency for Research on Cancer
- histologic types;
- oesophageal cancer trends
To monitor recent trends in mortality from oesophageal cancer in 33 European countries, we analyzed the data provided by the World Health Organization over the last 2 decades, using also joinpoint regression. For selected European cancer registration areas, we also analyzed incidence rates for different histological types. For men in the European Union (EU), age-standardized (world population) mortality rates were stable around 6/100,000 between the early 1980s and the early 1990s, and slightly declined in the last decade (5.4/100,000 in the early 2000s, annual percent change, APC = −1.1%). In several western European countries, male rates have started to level off or decline during the last decade (APC = −3.4% in France, and −3.0% in Italy). Also in Spain and the UK, which showed upward trends in the 1990s, the rates tended to level off in most recent years. A levelling of rates was observed only more recently in countries of central and eastern Europe, which had had substantial rises up to the late 1990s. Oesophageal cancer mortality rates remained comparatively low in European women, and overall EU female rates were stable around 1.1–1.2/100,000 over the last 2 decades (APC = −0.1%). In northern Europe a clear upward trend was observed in the incidence of oesophageal adenocarcinoma, and in Denmark and Scotland incidence of adenocarcinoma in men is now higher than that of squamous-cell carcinoma. Squamous-cell carcinoma remained the prevalent histological type in southern Europe. Changes in smoking habits and alcohol drinking for men, and perhaps nutrition, diet and physical activity for both sexes, can partly or largely explain these trends. © 2007 Wiley-Liss, Inc.
There are substantial geographical and temporal variations in oesophageal cancer mortality across Europe. In the 1960s, the highest rates for men were in France, but in the subsequent decades oesophageal cancer mortality has been steadily increasing in the UK, and mainly in Hungary and other countries of central and eastern Europe. However, there was some evidence for these rises to level off since the late 1990s. Oesophageal cancer mortality is much lower in women, and its trends have been unremarkable as compared to those in men, with the exclusion of Denmark, the Netherlands and the UK4 were increases have been observed.1, 2
To monitor recent trends in mortality from oesophageal cancer in Europe, we analyzed the data provided by the World Health Organization (WHO) over the last 2 decades, using also joinpoint regression,3 and discussed them in relation to main recognized risk factors for oesphageal cancer, particularly alcohol and tobacco consumption. For selected European cancer registration areas, we also gave incidence data for various histological types for the more recent years available.
Material and methods
Official death certification data from oesophageal cancer for 33 European countries and for the European Union (EU) overall4 the period 1980–2004 were derived from the World Health Organization (WHO) database available on electronic support.4 Data were presented for England and Wales and Scotland separately. Data for Estonia, Latvia, Lithuania, the Republic of Moldova and Ukraine were available only since 1981; for Croatia, the Czech Republic and Slovenia since the mid 1980s, and for Slovakia since the early 1990s. For Belgium, data were available only up to 1997; for Denmark up to 2001; for Italy, Slovakia and Sweden up to 2002; for France, Hungary and Portugal up to 2003.
The EU was defined as the 27 member states as since January 2007 (i.e., Austria, Belgium, Bulgaria, the Czech Republic, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, UK). Data for Cyprus were not available.
In the 2 decades considered, most countries utilized the 9th revision of the International Classification of Diseases (ICD),5 but some still used the 8th revision,6 and some adopted the 10th revision7 from the mid 1990s onwards. Since differences in the definition of oesophageal cancer between various revisions were minor, oesophageal cancer deaths were recoded for all countries according to the 9th revision of the ICD.
Estimates of the resident population, based on official censuses, were obtained from the same WHO database.4 From the matrices of certified deaths and resident populations, age-specific rates for each 5-year age group and calendar period were computed. Age-standardized rates per 100,000, at all ages and truncated 35–64 years, were computed using the direct method, and based on the world standard population.8 In a few countries, data were missing for part of 1 or more calendar years (as mentioned in Tables I and II). No extrapolation was made for missing data.
Joinpoint regression analysis was performed using the software provided by the Surveillance Research Program of the US National Cancer Institute.9 This analysis allows to identify points where a significant change in the linear slope (on a log scale) of the trend occurred.3 In joinpoint analysis, the best fitting points (the “joinpoints”) are chosen where the rate significantly changes. The analysis starts with the minimum number of joinpoints (e.g., 0 joinpoints, which is a straight line), and tests whether 1 or more joinpoints (up to 3) are significant and must be added to the model. In the final model each joinpoint informs of a significant change in the slope. The estimated annual percent change (APC) is then computed for each of those trends by fitting a regression line to the natural logarithm of the rates using calendar year as a regressor variable (i.e., given y = a + bx, where y = ln(rate) and x = calendar year, the APC is estimated as 100*(eb − 1)).
For selected European cancer registration areas, we also showed age-standardized (world population) incidence rates, derived from local or national cancer registry data,10 for different histological types of oesophageal cancer, i.e., squamous-cell, adenocarcinoma, other oesophageal cancers and unspecified oesophageal cancers.
Table I gives the overall age-standardized mortality rates from oesophageal cancer for men and women in various European countries and in the EU as a whole in 1980–1984, 1990–1994, 2000–2004, and the corresponding percent changes. For men in the EU, rates were stable around 6/100,000 between the early 1980s and early 1990s, and slightly declined in the last decade (5.4/100,000 in the early 2000s). In 1980–1984, the highest male rates were in France (13.0/100,000), Scotland (8.3/100,000), and the Russian Federation (7.8/100,000); the lowest ones in Bulgaria (1.2/100,000), Romania (1.6/100,000) and Greece (1.9/100,000). In 2000–2004, the highest male rates were in Scotland (10.9/100,000), England and Wales (8.5/100,000), and Hungary (8.4/100,000), followed by France, Ireland, the Netherlands and Slovakia (about 7–8/100,000), while the lowest ones were in Greece and Bulgaria (below 2.0/100,000), followed by Finland, Italy and Sweden (around 3/100,000). In EU women, rates were stable around 1.1–1.2/100,000 over the last 2 decades. In 1980–1984, the highest female rates were in Scotland (4.2/100,000) and Ireland (3.9/100,000), and the lowest ones in central and eastern European countries, such as Austria, Bulgaria, the Czech Republic, Latvia, Lithuania, and Romania (rates below 0.5/100,000). In 2000–2004, the highest female rates were in Scotland (4.0/100,000) and Ireland (3.2/100,000), and the lowest ones in Bulgaria, Estonia, Greece, Latvia, Malta, the Moldova Republic, Romania, Spain and Ukraine (below 0.5/100,000).
|1980–84||1990–94||2000–04||Deaths1||% change||% change||1980–84||1990–94||2000–04||Deaths1||% change||% change|
|Czech Republic (1985–89)||3.71||4.50||4.60||346||21.3||2.2||0.48||0.59||0.60||66||22.9||1.7|
|Moldova Republic (1981–82)||2.66||3.90||3.06||56||46.6||−21.5||0.90||0.58||0.43||12||−35.6||−25.9|
|Russian Federation (2001–04)||7.80||8.69||6.52||5341||11.4||−25.0||2.11||1.58||0.98||1667||−25.1||−38.0|
|UK, England and Wales||6.12||8.02||8.45||3943||31.1||5.4||2.86||3.20||3.12||2264||11.9||−2.5|
|European Union (2000–02)||5.63||5.83||5.39||20466||3.6||−7.6||1.17||1.16||1.13||6824||−0.9||−2.6|
Table II shows the corresponding values for middle-aged population (age 35–64 years). In the EU as a whole, male truncated oesophageal cancer mortality rates were around 9–10/100,000 between 1980–84 and 2000–02. In women, truncated rates were 1.4/100,000 in the early 1980s and 1.5/100,000 in 2000–02. In most countries the pattern of mortality rates was similar to those observed at all ages.
|1980–84||1990–94||2000–04||Deaths1||% change||% change||1980–84||1990–94||2000–04||Deaths1||% change||% change|
|Czech Republic (1985–89)||6.72||8.99||8.92||195||33.8||−0.8||0.47||0.66||0.93||21||40.4||40.9|
|Moldova Republic (1981–82)||5.47||7.88||6.02||33||44.1||−23.6||1.16||0.77||0.68||5||−33.6||−11.7|
|Russian Federation (2001–04)||12.50||15.69||11.43||2750||25.5||−27.2||2.30||1.74||1.02||321||−24.4||−41.4|
|UK, England and Wales||8.29||10.56||11.13||1162||27.4||5.4||3.36||3.46||3.22||344||3.0||−6.9|
|European Union (2000–02)||9.29||10.05||9.11||8709||8.2||−9.4||1.36||1.45||1.48||1491||6.6||2.1|
Figure 1 shows the trends in oesophageal cancer mortality at all ages and truncated 35–64 years in men from selected European countries between 1980 and 2004. Different scales have been used for each country in order to provide more easily interpretable trends. In the EU as a whole, male mortality rates were approximately stable in the last 2 decades. Declines were observed in France, Italy and Switzerland. After rises up to the early/mid 1990s, levelling off or declines in rates were also observed in Bulgaria, the Czech Republic, Germany, Hungary, Ireland, Norway, the Russian Federation, Spain and the UK. Upward trends were still observed in Belgium, Denmark, the Netherlands, Romania, England and Wales and Scotland.
Oesophageal cancer mortality trends in women from selected European countries at all ages and truncated 35–64 years over the period 1980–2004 are shown in Figure 2. The trends were stable in the EU as a whole at all ages, while they were slightly upwards in middle-aged women. Favourable trends were observed in Finland, Greece, Ireland, Italy, Portugal, the Russian Federation and Spain. In countries from central and northern Europe, such as Bulgaria, the Czech Republic, and the UK mortality increased up to the mid 1990s and tended to level off over most recent years. Female oesophageal mortality was upwards in Austria, Denmark, Germany, Hungary, the Netherlands and Norway.
The findings from the joinpoint regression analysis for oesophageal cancer mortality over the period 1980–2004 in selected largest European countries and in the EU as a whole are given in Table III. France and Italy had the largest falls in the last 2 decades, particularly in men (APC = −3.4 and −3.0%, respectively), while Denmark and the Netherlands had the highest rises (APC = +2.6% in men and +2.4% in women, +2.0% in men and +2.5% in women, in the 2 countries respectively). Trends were discontinuous in most other European countries considered, where, however, rates tended to level off in the last years, particularly in men. In the EU as a whole, rates slightly declined in men in the last decade (APC = −1.1%), and were stable between 1980 and 2002 in women (APC = −0.1%). The results of the joinpoint analysis for middle-aged men and women were consistent with those for overall mortality.
|Trend 1||Trend 2||Trend 3||Trend 4||Trend 1||Trend 2||Trend 3||Trend 4|
|UK, England and Wales||1980–1993||2.61||1993–2004||0.2||1980–1993||1.21||1993–2004||−0.5|
|UK, England and Wales||1980–1994||2.11||1994–2004||0.0||1980–2004||−0.2|
Figure 3 gives trends in age-adjusted incidence rates for various histological types of oesophageal cancer in men for selected European cancer registration areas between 1980 and 1997. In northern Europe (Denmark, Finland, Norway, Sweden, Scotland, but also Switzerland), a clear upward trend was observed in oesophageal adenocarcinoma, and in Denmark and Scotland men incidence of adenocarcinoma is now higher than that of squamous-cell carcinoma. The pattern is different in central and southern Europe, where the rise of adenocarcinoma is much smaller, and squamous-cell cancer remains the predominant histological type, despite falls in Italy and mostly in France.
Figure 4 gives the corresponding figures for women. Given the low rates, trends are less stable and hence more difficult to interpret. Still, some rise in adenocarcinoma is observed in most registration areas considered, and particularly in Scotland. Substantial rises in squamous-cell oesophageal cancer incidence were registered in Denmark, Norway and, to a lesser degree, France, Switzerland and Scotland.
Figure 5 gives the trends in the prevalence of alcohol consumption (litres of ethanol per year) in adult populations (≥15 years) from selected European countries during the period 1961 and 2001. A steady decrease in alcohol consumption was observed in France since the early 1960s, Italy since the early 1970s, and in Portugal, and Spain since the mid 1970s. Alcohol consumption increased between the 1960s and the mid-late 1980s in Belgium, Bulgaria, the Czeck Republic, Denmark, Germany, Hungary, the Netherlands, Poland and Romania, to level off thereafter, while it was still upward in Finland, Ireland and the UK in the last decade. Alcohol consumption showed no clear pattern of trends in other countries considered.
Figure 6 shows the trends in the number of cigarettes smoked per year in populations of both sexes combined from selected European countries between 1970 and 1999. In the last 3 decades, cigarette consumption has been decreasing in countries from northern Europe including Austria, Belgium, Finland, Ireland, Sweden and particularly the UK. A more recent decline was also observed in countries like France and Italy. Conversely, smoking was still increasing in Bulgaria, Greece, Portugal and Spain.
There are at least 4 main findings from this updated analysis of oesophageal cancer incidence and mortality trends in Europe. First, after several decades of appreciable rises, male oesophageal cancer mortality has started to level off or decline since the late 1980s or 1990s in several western European countries. In a few countries still showing upward trends in the 1990s, like Spain and the UK, the rise became less steep over the last years. Second, in central and eastern Europe and in the Russian Federation, male mortality rates—which were substantially upwards until the mid 1990s—have tended to level off over the last years. Still, Hungary and a few other countries in this area of the continent presently have among the highest rates across Europe. Third, oesophageal cancer rates remain comparatively low in European women, and decreased over the last decade in several Western countries. Fourth, oesophageal adenocarcinoma incidence has risen in men, particularly in northern Europe, and is now the first histotype for incidence in Denmark and Scotland. Although the increase in Scottish men is probably real, its interpretation is hampered by the decrease of the cancers with unspecified morphology.
Thus, the pattern of oesophageal cancer mortality has largely changed over the last 2 decades across Europe. In the early 1980s, male oesophageal cancer mortality was over 2-fold in France as compared to England and Wales, and Italy had intermediate to high rates, whereas in the last few years mortality was higher in England than in France, and Italy had one of the lowest rates. These trends in mortality from oesophageal cancer partly reflect the patterns in alcohol drinking, which declined by over 50% in Italy or France over the last 2 decades, but has steadily increased in Britain.11, 13, 14 Likewise, the widespread favourable trends in mortality rates over the last few years reflect the fall in tobacco consumption in men from most (Western) European countries during the last few decades.15 The pattern of tobacco is more difficult to interpret with reference to oesophageal cancer rates, given the diverging trends in consumption in men and women over the last few decades. On an individual level, oesophageal cancer risk declines in the few years after stopping smoking,16 while the pattern of risk is less clear after stopping drinking.17, 18 Still, on a population level, oesophageal cancer rates appear to be consistently related to changes in alcohol drinking.14
Oesophageal cancer includes 2 major histological types, squamous-cell cancer, and adenocarcinoma. Both are directly related to tobacco smoking, but only squamous-cell cancer to alcohol drinking, while adenocarcinoma risk is increased by overweight, obesity, lack of physical activity and gastro-oesophageal reflux.19–23 Following the increased prevalence of overweight and inactivity in North America24, 25 and northern Europe,26–28 increases in oesophageal adenocarcinoma have been reported in recent periods. At least part of the unfavourable trends in Denmark, the Netherlands, Scotland and other northern European countries are due to increased incidence of adenocarcinoma.26–30
The role of other risk factors on oesophageal cancer mortality on a national level is smaller than that of tobacco and alcohol, and remains largely unquantified. Some aspects of diet and nutrition, such as low fruit and vegetable consumption, have been directly related to the risk of oesophageal cancer31, 32 and may account for a non negligible fraction of oesophageal cancers in some European populations.33 Oesophageal cancer trends are also influenced by improvements in diagnosis and disease management. Although the prognosis of oesophageal cancer has been poor—with a relative survival of between 5 and 10% up to the 1980s—some recent data showed the existence of appreciable improvements for both histologic types of oesophageal cancer over the last decades,34–38 probably as a consequence of earlier diagnosis and detection through wider adoption of endoscopy, as well as to advancements in treatment of the disease. The impact of such improvements on oesophageal cancer mortality is, however, difficult to evaluate.
It is unlikely that trends in oesophageal cancer mortality in Europe have been appreciably influenced by changes in diagnosis and certification of the disease, since oesophageal cancer is easy to diagnose, and no major change has been introduced in certification of this neoplasm across the ICD revisions considered in the present analysis.
In conclusion, therefore, after decades of rises, oesophageal cancer mortality has started to level off or decline for both sexes in several European countries over the last decades. In northern Europe, however, adenocarcinoma has shown substantial rises in incidence. Changes in smoking and alcohol drinking for men, and perhaps nutrition, diet and physical activity for both sexes, can partly or largely explain these trends.
This work was conducted with the contribution of the Italian and Swiss Leagues Against Cancer, the Swiss Foundation for Research Against Cancer, and the Italian Association for Cancer Research. The work of this article was undertaken while CLV was a Senior Fellow at the International Agency for Research on Cancer. The authors thank Mrs. I. Garimoldi for editorial assistance.
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- 7World Health Organization. International statistical classification of disease and related health problems, 10th revision. Geneva: World Health Organization, 1992.
- 8Comparison between registries: age-standardized rates. In: WaterhouseJAH,MuirCS,ShanmugaratnamK,PowellJ,PeachamD,WhelanS, eds. Cancer incidence in five continents,vol. 4. IARC Sci Publ. No. 42. Lyon: IARC, 1982. 671–5., .
- 9National Cancer Institute. Joinpoint Regression Program, version 3.0. Available at: http://srab.cancer.gov/joinpoint 2005.
- 10Cancer incidence in five continents, vols. 1–8. [Cancer base No.7 IARC Press Lyon]. France: International Agency for Research on Cancer, 2005., , , .
- 11World Health Organization Statistical Information System. Health topics. Alcohol drinking. Available at: http://www.who.int/topics/alcohol_drinking/en. 2006.
- 12World Health Organization Regional Office for Europe. European health for all database (HFA-DB). Available at: http://data.euro.who. int/hfadb. 2007.
- 23Smoking and cancer of the oesophagus tobacco and public health: science and policy. In: BoyleP,GrayN,KenningfieldJ,SeffinJ,ZatonskiW, eds. Oxford: Oxford University Press, 2004; 383–96..