Trends in laryngeal cancer mortality in Europe
Article first published online: 22 FEB 2006
Copyright © 2006 Wiley-Liss, Inc.
International Journal of Cancer
Volume 119, Issue 3, pages 673–681, 1 August 2006
How to Cite
Bosetti, C., Garavello, W., Levi, F., Lucchini, F., Negri, E. and LaVecchia, C. (2006), Trends in laryngeal cancer mortality in Europe. Int. J. Cancer, 119: 673–681. doi: 10.1002/ijc.21855
- Issue published online: 8 MAY 2006
- Article first published online: 22 FEB 2006
- Manuscript Accepted: 5 DEC 2005
- Manuscript Received: 14 OCT 2005
- Italian and Swiss Leagues Against Cancer
- The Swiss Foundation for Research Against Cancer
- The Italian Association for Cancer Research
- laryngeal cancer;
After a steady increase since the 1950s, laryngeal cancer mortality had tended to level off since the early 1980s in men from most European countries. To update trends in laryngeal cancer mortality in Europe, age-standardized (world standard) mortality rates per 100,000 were derived from the WHO mortality database for 33 European countries over the period 1980–2001. Jointpoint analysis was used to identify significant changes in mortality rates. In the European Union (EU) as a whole, male mortality declined by 0.8% per year between 1980 and 1989, by 2.8% between 1989 and 1995, by 5.3% between 1995 and 1998, and by 1.5% thereafter (rates were 5.1/100,000 in 1980–1981 and 3.3/100,000 in 2000–2001). This mainly reflects a decrease in rates in men from western and southern European countries, which had exceedingly high rates in the past. Male laryngeal mortality rose up to the early 1990s, and leveled off thereafter in several countries from central and eastern Europe. In 2000–2001 there was still a 10–15-fold variation in male laryngeal mortality between the highest rates in Croatia (7.9/100,000) and Hungary (7.7/100,000) and the lowest ones in Sweden (0.5/100,000) and Finland (0.8/100,000). Laryngeal cancer mortality was comparatively low in women from most European countries, with stable rates around 0.3/100,000 in the EU as a whole over the last 2 decades. Laryngeal cancer trends should be interpreted in terms of patterns and changes in exposure to alcohol and tobacco. Despite recent declines, the persistence of a wide variability in male laryngeal cancer mortality indicates that there is still ample scope for prevention of laryngeal cancer in Europe. © 2006 Wiley-Liss, Inc.
Male laryngeal cancer is one of the cancers with the largest variations in mortality across European countries.1, 2 In the 1950s, France and a few southern European countries (Italy and Spain) had the highest rates. In these countries, male mortality from laryngeal cancer had long been increasing, and reached a peak in the early to mid 1980s.2 Substantial increases in rates between the 1950s and the 1990s were also observed in men from central and eastern European countries, including Hungary, Poland and the Russian Federation.2, 3 Mortality rates were traditionally lower in Scandinavian countries.1 Laryngeal cancer is the neoplasm with the largest male-to-female ratio,1, 4, 5 and hence, trends in women are unremarkable compared to those in men in most European countries, with the exception of Denmark, Ireland and the United Kingdom.2
To further monitor recent trends in mortality from laryngeal cancer in Europe, we analyzed the data provided by the World Health Organization (WHO) over the last 2 decades, using also jointpoint regression analysis.6 These trends are discussed with reference to changes in the exposure to tobacco smoking and alcohol drinking, the main recognized risk factors for laryngeal cancer in developed countries.7, 8
Material and methods
Official death certification data from laryngeal cancer for 33 European countries for the period 1980–2001 were derived from WHO the database available on electronic support.9 Besides the United Kingdom as a whole, data were presented also for England and Wales, Scotland and Northern Ireland. 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, France and the Netherlands up to 2000.
The EU was defined as the union of 25 member states since May 2004 (i.e., Austria, Belgium, the Czech Republic, Cyprus, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden and UK). Data for Cyprus were not available.
In the 2 decades considered, most countries utilized the Ninth revision of the International classification of diseases (ICD),10 but some still used the Eighth revision,11 and some adopted the Tenth revision from 1995 onwards.12 Since differences in the definition of laryngeal cancer between various revisions were minor, laryngeal cancer deaths were recoded for all countries according to the Ninth revision of the ICD.11
Estimates of the resident population, generally based on official censuses, were obtained from the same WHO database.9 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 were based on the world standard population.13 In a few countries, data were missing for part of one or more calendar years. 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.14 This analysis allows to identify points where a significant change in the linear slope of the trend occurred.6 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 one 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 (EAPC) 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.
Table I gives overall age-standardized laryngeal mortality rates for men and women in various European countries and in the EU as a whole in 1980–1981, 1990–1991, 2000–2001, the corresponding percent change in rates and the number of deaths for the last year available in each country. For men in the EU, mortality declined by 10% between 1980–1981 and 1990–1991 (from 5.1 to 4.6/100,000), and by 28% between 1990–1991 and 2000–2001 to reach an overall age-standardized rate of 3.3/100,000 in 2000–2001. In 1980–1981, the highest rates for men were observed in France (10.9/100,000) and Spain (7.6/100,000), followed by Italy and the Russian Federation (rates over 6/100,000). The lowest rates were in Sweden (0.8/100,000), Norway (1.0/100,000) and England and Wales (1.7/100,000). In 2000–2001, the highest rates were in Croatia, Hungary and the Russian Federation (about 7–8/100,000), and the lowest ones in Nordic countries, such as Finland, Norway and Sweden (below 1.0/100,000).
|1980–1981||1990–1991||2000–2001||Number of deaths1||% Change (1991/81)||% Change (2001/91)||1980–1981||1990–1991||2000–2001||Number of deaths1||% Change (1991/81)||% Change (2001/91)|
|Republic of Moldova||5.924||6.10||6.02||100||3.0||−1.3||1.104||0.17||0.17||2||−84.6||0.0|
|UK, England and Wales||1.71||1.65||1.32||612||−3.5||−20.0||0.38||0.32||0.24||142||−15.8||−25.0|
In women from the EU, laryngeal cancer mortality rates were stable around 0.3/100,000 over the last 2 decades. In 1980–1981, the highest rates in women were in Ireland (0.8/100,000) and Romania (0.5/100,000), and the lowest ones in Nordic countries, such as Finland, the Netherlands, Norway and Sweden (rates below 0.2/100,000). The highest rates in 2000–2001 were observed in the Republic of Moldova (1.10/100,000), Hungary (0.7/100,000) and Poland (0.5/100,000), while all other countries showed rates between 0.2 and 0.4/100,000.
Table II gives corresponding values for truncated rates (age 35–64 years). In the EU as a whole, although starting from a higher level (9.3/100,000), the trend in male laryngeal cancer mortality was similar to that registered at all ages, with a 10% fall between 1980–1981 and 1990–1991, and a 30% decline thereafter (5.8/100,000 in 2000–2001). Laryngeal cancer mortality in middle-aged women from the EU was stable between 1980–1981 and 2000–2001 around 0.5/100,000.
|1980–1981||1990–1991||2000–2001||Number ofdeaths1||% Change (1991/81)||% Change (2001/91)||1980–1981||1990–1991||2000–2001||Number of deaths1||% Change (1991/81)||% Change (2001/91)|
|Republic of Moldova||12.964||13.99||12.97||67||8.0||−7.3||3.094||0.33||0.30||1||−89.3||−9.1|
|UK, England and Wales||2.38||2.32||1.94||204||−2.5||−16.4||0.67||0.44||0.32||39||−34.3||−27.3|
Figure 1 shows the trends in laryngeal cancer mortality at all ages and truncated 35–64 years in men from selected European countries between 1980 and 2001. Different scales have been adopted for each country in order to provide more readable and interpretable trends. A fall in male laryngeal cancer mortality was observed since the early 1980s in the EU as a whole, reflecting a decrease in western and southern European countries, including Italy, Spain and mostly France, which had exceedingly high rates in the past. Favorable trends were also observed in northern European countries, including Austria, England and Wales, Ireland, Finland, Sweden and Switzerland. Male laryngeal mortality rose up to the early 1990s in countries from central and eastern Europe, such as the Czech Republic, Hungary, Poland, Romania, as well as in the Russian Federation, and leveled off only thereafter. Upward trends were still observed in Bulgaria and Scotland over the last 2 decades. In most European countries, trends in male truncated rates over the period 1980–2001 were consistent with the overall ones, the only exception being Ireland, for which middle-age rates seemed to steadily increase up to the most recent years.
Figure 2 gives the trends in age-specific rates from 30–34 to 80–84 years for laryngeal cancer in men, plotted against the central year of birth from selected largest European countries, plus Hungary characterized by the highest rates in 2000–2001. In the EU as a whole, the generations born up to 1920 tended to have higher mortality as compared to the previous ones. All age-specific rates tended however to decline over recent calendar periods. Similar patterns were observed in France and Italy, which showed particularly evident decreases in mortality in more recent generations, while in the UK a moderate decline of rates was present since earlier generations of men. In countries of central and eastern Europe (i.e., Hungary, Poland, the Russian Federation, but also Germany), age-specific rates rose in the earlier calendar periods and declined thereafter.
Laryngeal cancer mortality trends in women from selected European countries at all ages and truncated 35–64 years over the period 1980–2001 are shown in Figure 3, using a different scale. In the EU as a whole, female mortality rates were approximately stable in the last 2 decades. Declining trends between the 1980s and the 2000s were observed in France, Ireland, Italy, Portugal, England and Wales, as well as in Romania and the Russian Federation. In a few countries, such as Denmark, Germany, Hungary and Scotland, laryngeal cancer mortality rates in women rose up to the mid-late 1990s, but leveled off thereafter. Only The Netherlands showed persistent upward trends over the last 2 decades, while rises were observed in Sweden and Switzerland in the last quinquennium. Trends in middle-aged women were similar—although more pronounced—to those of all women for most European countries. Only in Austria and particularly Scotland, female truncated rates rose over the last 2 decades, and in Sweden and Switzerland, truncated rates showed a larger increase in the last quinquennium.
The findings from the jointpoint regression analysis over the period 1980–2001 for laryngeal cancer mortality in selected largest European countries and in the EU as a whole are given in Table III. At all ages, male laryngeal cancer rates declined by 0.8% per year between 1980 and 1989, by 2.8% between 1989 and 1995, by 5.3% between 1995 and 1998, and by 1.5% thereafter. In middle-aged men, after a rise between 1980 and 1983 (by 1.4% per year), rates declined by 1.7% between 1983 and 1991, and by 4.1% thereafter. In women, a continuous slight decline was observed over the period considered (EAPC = 0.69% and 0.30% at all ages and in middle-age, respectively). Considering major European countries separately, a decline in rates was observed in Italy (−0.68) and particularly France (−2.79) between 1980 and 1986; stronger declines were observed thereafter (−4.70 in Italy and −5.64 in France). Increasing trends were found in Germany (1.42), England and Wales (0.13) and particularly in Hungary (3.70), Poland (2.62) and the Russian federation (2.55) up to the early 1990s. A decline in laryngeal cancer rates was observed thereafter also in these countries of central and eastern Europe (EAPC between −3.9 and −1.7). Similar patterns were observed in middle-aged men.
|Trend 1||Trend 2||Trend 3||Trend 4|
|UK, England and Wales|
The present comprehensive analysis indicates and further quantifies a decline of laryngeal cancer mortality in men from several European countries over the last 2 decades. In particular, male mortality rates substantially decreased in western and southern European countries, such as France, Italy and Spain, which had the highest rates in the past. In various countries from central and eastern Europe, including Hungary, Poland and the Russian Federation, steady upward rates in male laryngeal cancer mortality were registered up to the late 1990s, but a tendency to level off was observed over more recent years. Some persisting upward trends were seen only in Bulgaria and Scotland. In 2000–2001 there was still a 10–15-fold variation in male laryngeal mortality between the highest rates in Croatia (7.91) and Hungary (7.68) and the lowest ones in Sweden (0.51) and Finland (0.78).
In the interpretation of the data presented, it is important to consider problems related to random variation, which are clearly greater in relation to smaller populations. Moreover, there are problems of death certification reliability and validity in various countries. Despite potential uncertainties in the distinction between hypophaynx and epilarynx,15, 16 and a moderate degree of overreporting of this cause of death in the 1970s,17 death certification for laryngeal cancer is sufficiently reliable to permit meaningful inference on trends for most European countries.17, 18 As no major change has been introduced in the classification and coding of laryngeal cancer across subsequent revisions of ICD, it is unlikely that these trends have been materially influenced by changes in diagnosis and certification of the disease. Furthermore, rates in the middle-aged population are less likely to be affected by certification problems.
The geographical variations of mortality from laryngeal cancer and the trends in rates likely reflect differences in tobacco and alcohol consumption across European countries and the changes in subsequent calendar years in the pattern of exposure to these 2 risk factors. The stronger similarities of laryngeal mortality trends with those of other alcohol-related cancers (such as those of the oral cavity, pharynx and esophagus), rather than with those of lung cancer,2, 19 confirm that alcohol drinking is an important determinant of the geographical and temporal patterns of laryngeal cancer, either independently or jointly with tobacco smoking.20 Thus, the recent favorable trends in male laryngeal cancer mortality in former high-risk countries reflect the downward trends not only in alcohol consumption (by over 50% in France and Italy between 1960 and 2000) but also in tobacco consumption in men from some of these countries.21, 22, 23 Conversely, the upsurge in laryngeal mortality registered in Hungary and other eastern European countries up to the late 1990s is due to the increase in both tobacco consumption and alcohol drinking.21, 22, 23 Such countries have now the highest laryngeal mortality rates on a European scale, and the control of laryngeal cancer, as well as of other alcohol- and tobacco-related cancers, remains a major public health problem in these areas.24 The steady unfavorable trends in men from Scotland seem to be essentially attributable to alcohol drinking patterns, giving the discrepancy with trends in lung cancer mortality over the same period and more close similarities with trends for other alcohol-related neoplasms (such as oral, pharyngeal and esophageal cancer).2
Earlier diagnosis and better adoption of integrated therapeutic schemes may also have favorably influenced laryngeal cancer survival rates and consequently mortality trends in various areas of the continent. Five-year survival from laryngeal cancer is over 60% in both men and women from Europe, although it has been showed to be higher in northern Europe countries, than in eastern European ones,25 as indicated also by a higher incidence to mortality ratio.1 Improvements in survival from laryngeal cancer has been reported in the last decades in some, but not all, European countries,26, 27, 28, 29, 30 and could have had some favorable impact on mortality trends. Thus, the changes over time, as well as the variability of survival across European countries, could partly explain the observed trends in mortality from laryngeal cancer. Moreover, the discrepancy between trends in mortality from laryngeal and lung cancer in several European countries (including France, Portugal and Spain, and also Nordic countries) could be explained, besides by a role of alcohol consumption, by a difference in the survival for these 2 neoplasms.2, 26 However, survival data should be cautiously considered, since improvements in the diagnosis may advance the time at diagnosis, without prolonging life, thus affecting incidence more than mortality rates.
Although a different role of various types of alcoholic beverages on laryngeal cancer risk has been suggested,24, 31, 32 it is now clear that the risk of laryngeal cancer is mainly associated to the quantity of ethanol ingested.33 Thus, elevated laryngeal cancer mortality rates were found both in countries with high consumption of wine (such as France and Italy), hard drinks and fruit-derived spirits (such as Hungary, the Russian Federation and other eastern European countries).
Diet may also had an impact on laryngeal cancer mortality, and particularly consumption of vegetables and fruits, which have been related to a reduced laryngeal cancer risk, may have had some effect in reducing the mortality from this neoplasm.34, 35 The availability of vegetables and fruits has indeed increased in western Europe and mostly in former nonmarket economies of eastern Europe over the last few decades.36, 37
Laryngeal cancer mortality in women is substantially lower as compared to that in men. Trends were stable—or even slightly declining—over the last 2 decades in the EU as a whole and in most European countries, although rises were observed in some countries, such as Austria, Hungary, the Netherlands and Scotland. Further, recent rises were observed in Sweden and Switzerland, particularly in middle-aged women. As for men, the trends in women reflect the patterns of tobacco and mainly alcohol consumption in European women, and similarities are observed with other tobacco and alcohol-related cancers.2
In conclusion, this update analysis of laryngeal cancer mortality across Europe indicates that laryngeal cancer mortality had tended to decrease since the early 1980s after a steady increase since the 1950s in men from most European countries, particularly from western and southern Europe. More recent and smaller declines in trends were also observed in central and eastern Europe. However, it shows that a wide variability in male laryngeal cancer mortality persists despite the recent favorable trends, indicating that there is still ample scope for prevention of laryngeal cancer mortality in Europe.
The authors thank Mrs. M.P. Bonifacino for editorial assistance.
- 7IARC. Monographs on the evaluation of carcinogenic risks to humans. Alcohol drinking. vol. 44. Lyon: IARC, 1988.
- 8IARC. Monographs on the evaluation of carcinogenic risks to humans. Tobacco smoke and involuntary smoking. vol. 83. Lyon: IARC, 2004.
- 10WHO. International classification of disease, 8th revision. Geneva: World Health Organization, 1967.
- 11WHO. International classification of disease, 9th revision. Geneva: World Health Organization, 1977.
- 12WHO. International statistical classification of disease and related health problems, 10th revision. Geneva: World Health Organization, 1992.
- 13Comparison between registries: age-standardized rates. In: WaterhouseJAH, MuirCS, ShanmugaratnamK, PowellJ, PeachamD, WhelanS, eds. Cancer incidence in five continents. vol. 4 Lyon: IARC, 1982. IARC Scientific Publication no. 42, 671–5., .
- 14National Cancer Institute. Joinpoint regression program, version 2.7, September 2003. Available at http://srab.cancer.gov/joinpoint.
- 15Cancer of the larynx/hypopharynx, tobacco and alcohol: IARC international case-control study in Turin and Varese (Italy), Zaragoza and Navarra (Spain), Geneva (Switzerland) and Calvados (France). Int J Cancer 1988; 41: 483–91., , , , , , , , , , , , et al.
- 22WHO. Tobacco or health. A global status report. Geneva: World Health Organization, 1997.
- 23World Health Organization Statistical Information System. Health topics. Alcohol drinking. Geneva: WHO. Available at: www3.who. int/whosis/menu.cfm.
- 34World Cancer Research Fund in association with the American Institute for Cancer Research. Food, nutrition and the prevention of Cancer: a global perspective. Washington, DC: World Cancer Research Fund, 1997.