The oral cancer epidemic in central and eastern Europe

Authors

  • Werner Garavello,

    Corresponding author
    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Clinica Otorinolaringoiatrica, DNTB, Università Milano-Bicocca, Monza, Italy
    • Istituto di Ricerche Farmacologiche “Mario Negri”, Via Giuseppe La Masa 19. 20156 Milan, Italy
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    • Tel.: +390239014652, Fax: +39-0233200231

  • Paola Bertuccio,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
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  • Fabio Levi,

    1. Unité d'Epidémiologie du Cancer et Registres Vaudois et Neuchâtelois des Tumeurs, Institut de Médecine Sociale et Préventive, Centre Hospitalier Universitaire Vaudois et Faculté de Biologie et Médecine, Falaises 1, Lausanne, Switzerland
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  • Franca Lucchini,

    1. Unité d'Epidémiologie du Cancer et Registres Vaudois et Neuchâtelois des Tumeurs, Institut de Médecine Sociale et Préventive, Centre Hospitalier Universitaire Vaudois et Faculté de Biologie et Médecine, Falaises 1, Lausanne, Switzerland
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  • Cristina Bosetti,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
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  • Matteo Malvezzi,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Istituto di Statistica Medica e Biometria, “G.A. Maccacaro”, Università degli Studi di Milano, Milan, Italy
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  • Eva Negri,

    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
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  • Carlo La Vecchia

    1. Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
    2. Istituto di Statistica Medica e Biometria, “G.A. Maccacaro”, Università degli Studi di Milano, Milan, Italy
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Abstract

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975–2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000–2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000–2004. In France and Italy—which had the highest rates in the past—male rates have steadily declined during the last two decades (annual percent change, APC = −4.8% in 1998–2004 in France and −2.6% in 1986–2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC = 6.9% in 1975–1993 and 1.4% in 1993–2004) and Slovakia (16.9/100,000; APC = 0.14% in 1992–2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.3/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC = 4.7% in 1975–2004) and Denmark (1.6/100,000; APC = 1.3% in 1975–2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe.

Oral and pharyngeal cancer is the 7th most common cancer in Europe, and the 9th site of cancer death, with an estimated number of 67,000 incident cases and 26,000 deaths in 2004.1 In the European Union (EU) as a whole, male mortality from oral and pharyngeal cancer peaked in the early 1990's and levelled off in the late 1990's around 6/100,000 men. Mortality rates moderately increased in women to reach 1.1/100,000.2–4 In the late 1990's, there was, however, substantial variation in patterns and trends of oral cancer mortality across Europe. The highest rates for men in countries of central Europe (Hungary, Slovakia) were almost 10-fold higher than the lowest ones in Finland, Sweden and Greece, and the range of variation was about 4-fold in women. These patterns and trends can largely be related to changes in consumption of tobacco and alcohol, i.e., the two major recognized risk factors for oral and pharyngeal cancer.5–7 Countries like France and Italy, which had the highest alcohol consumption up to the early 1980's, but where alcohol drinking has substantially declined over the last few decades,8 showed favourable trends in oral cancer mortality over the last 20 years, whereas trends were less favourable in most countries from northern Europe, where alcohol drinking has increased. The most unfavourable trends and the highest mortality from oral and pharyngeal cancer, however, were reported in central and eastern Europe.

To provide an updated analysis of oral and pharyngeal cancer mortality in Europe, we considered rates in selected European countries between 1975 and 2004. For the largest countries, we also analyzed changes over time, using joinpoint regression analysis.9 A specific focus was given to central European countries.

Material and Methods

Official death certification data from oral and pharyngeal cancer for 38 European countries in the period 1975–2004 were derived from the World Health Organization (WHO) database available on electronic support.10 Besides the United Kingdom, data were considered for England and Wales, Northern Ireland and Scotland separately. Data for Belarus, Lithuania, the Republic of Moldova, the Russian Federation and Ukraine were available only since the early 1980's; for Croatia, the Czech Republic and Slovenia since the mid 1980's, and for Slovakia since 1992. For Denmark, data were only available up to 2001; for Belarus, Bulgaria, Italy, Macedonia and Portugal up to 2003.

The EU was defined as the 27 member states, 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, United Kingdom. Data for Cyprus were not available and those for Belgium were only available up to 1997, and were therefore excluded.

During the calendar period considered (1975–2004), three different Revisions of the International Classification of Diseases (ICD) were used.11–13 As differences in classifications between various Revisions were minor, oral and pharyngeal cancer deaths were re-coded for all countries according to the 10th Revision of the ICD (ICD-10: C00–C14).13

Estimates of the resident population, based on official censuses, were obtained from the same WHO database.10 From the matrices of certified deaths and resident populations, we computed age-specific rates for each 5-year age group (from 0, 1–4 to 85+ years) and calendar period. Age-standardized rates per 100,000 men and women, at all ages and truncated 35–64 years, were computed using the direct method, on the basis of the world standard population.14 In a few countries, mortality data were missing for 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.15 This analysis allowes to identify points where a significant change in the linear slope (on a log scale) of the trend occurred.9 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 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)).

Results

Table 1 gives the overall age-standardized mortality rates from oral and pharyngeal cancer in men and women from various European countries and in the EU as a whole in 1990–1994 and 2000–2004, and the corresponding percent changes. Figure 1a shows the histograms of oral and pharyngeal cancer mortality in various European countries for the last calendar period considered for men and women at all ages and at 35–64 years. For EU men, rates declined by 8% between the early 1990–1994 and 2000–2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000–2004. In 1990–1994, the highest male rates were in Hungary (17.1/100,000), Slovakia (16.0/100,000) and France (12.4/100,000); the lowest ones in Greece and Iceland (1.8/100,000), and Finland (2.2/100,000). In 2000–2004, the highest male rates were in Hungary (21.1/100,000) and other countries from central and eastern Europe, such as Slovakia (16.9/100,000), the Republic of Moldova, Lithuania, Ukraine and Croatia (around 10–11/100,000), while the lowest ones were in Nordic countries, such Iceland, Sweden, Finland (around 2/100,000), the United Kingdom (2.8/100,000) and Greece (1.8/100,000). Oral and pharyngeal cancer mortality in men declined over the last decade in several large European countries, including France (with a rate of 8.6/100,000 in the early 2000's), Spain (6.0/100,000), Germany (5.7/100,000) and Italy (4.3/100.000). Persisting rises were, however, observed in several central and eastern European countries, including in particular Hungary, but also Belarus, Lithuania and Romania. Rates were much lower in women, but increased moderately from 1.08 to 1.14/100,000 over the last decade in the EU as a whole. In 2000–2004, the highest rates for women were in Hungary, too (3.3/100,000), followed by Denmark (1.6/100,000) and Scotland (1.4/100,000), and the lowest ones were in Bulgaria (0.8/100,000) and Greece (0.7/100,000).

Figure 1.

Average overall (a) and 35–64 years (b) age-standardized (world population) death certification rates from oral and pharyngeal cancer per 100,000 in the European Union and selected European countries, 2000–2004 (unless otherwise mentioned).

Table 1. Overall age-standardized (world population) mortality rates from oral and pharyngeal cancer per 100,000 men and women in selected European countries and in the European Union, in 1990–1994, 2000–2004 (unless otherwise mentioned in parenthesis), and corresponding percent changes in rates
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Corresponding figures for the truncated 35–64 years rates are given in Table 2 and Figure 1b. The strong excess and the upwards trends in oral and pharyngeal cancer mortality over the last decade in Hungary and other selected eastern European countries were even more evident. Male truncated rates reached 55.3/100,000 in Hungary, 40.8/100,000 in Slovakia, 22 to 25/100,000 in Belarus, Croatia, Lithuania, Moldova, Romania and Ukraine. For women, too, the highest truncated rate was in Hungary (8.0/100,000).

Table 2. Age-standardized (world population) mortality rates from oral and pharyngeal cancer per 100,000 men and women aged 35–64 years in selected European countries and in the European Union, in 1990–1994, 2000–2004 (unless otherwise mentioned in parenthesis), and corresponding percent changes in rates
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Findings from joinpoint regression analysis over the period 1975–2004 for oral and pharyngeal cancer mortality at all ages and truncated 35–64 years from selected European countries and the EU as a whole are given in Figure 2 and Table 3 in men, and Figure 3 and Table 4 in women. In the EU, overall male mortality rates from oral and pharyngeal cancer rose by 2.09% per year between 1975 and 1984, by 0.98% between 1984 and 1993, but declined by 1.32% between 1993 and 2004. In women, oral and pharyngeal cancer mortality rose by 0.93% per year up to 2000, and levelled off thereafter. Male rates were favourable over recent years in countries from southern Europe, which had the highest rates in the past, such as France (APC = −4.81%) between 1998 and 2004, and Italy (APC = −2.63%) between 1986 and 2003, but were still rising over most recent years in Hungary, Belarus, Lithuania, Romania, Slovakia as well as in Denmark. In Hungary, oral and pharyngeal cancer mortality in women increased by 4.67% per year during all the calendar period considered. Several other countries also showed upwards trends, though, given the low rates in women, much fewer joinpoints emerged from the models. The pattern was similar for truncated rates up to the late 1990's, but tended to be more favourable for men in several countries over recent years.

Figure 2.

Joinpoint analysis for oral and pharyngeal cancer mortality in men (all ages and aged 35–64 years) from the European Union and selected European countries, 1975–2004. All ages +—+; 35–64 years □—□.

Figure 3.

Joinpoint analysis for oral and pharyngeal cancer mortality in women (all ages and aged 35–64 years) from the European Union and selected European countries, 1975–2004. All ages +—+; 35–64 years □—□.

Table 3. Joinpoint analysis for oral and pharyngeal cancer mortality in men (at all ages and truncated 35–64 years) from selected European countries and the European Union, 1975–20041
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Table 4. Joinpoint analysis for oral and pharyngeal cancer mortality in women (at all ages and truncated 35–64 years) from selected European countries and the European Union, 1975–20041
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Figure 4 gives the trends in male age-specific mortality rates from oral and pharyngeal cancer from 30–34 to 80–84 years plotted against year of birth in the EU and in 7 major European countries. In the EU, male rates were rising in cohorts born before 1945–1950 and falling in more recent ones, across subsequent age groups. The decline started in earlier cohorts (i.e., those born around 1935–1940) in Italy and France, and later in Germany, the United Kingdom, Poland and the Russian Federation. In Hungary, oral cancer mortality was substantially upwards up to the cohort born around 1960, and some hint of decline was observed only in most recent ones, although based on small absolute number of deaths.

Figure 4.

Trends in age-specific death certification rates from oral and pharyngeal cancer per 100,000 men in the European Union and 7 major European countries by year of birth. Age groups from 30–34 to 80–84 years.

Discussion

The main finding from this updated analysis of oral and pharyngeal cancer mortality in Europe is the strong excess in Hungary, where the rate for middle aged men was 55/100,000, comparable to those of lung cancer in several western countries (i.e., 50 to 60/100,000 in Germany, Italy and the United Kingdom).16, 17 Only in most recent cohorts (i.e., those born after 1960) there was some initial hint of reversal of trends. Male rates appreciably decreased in southern European countries, such as France, Italy and Spain, which had the highest rates in the past, but not in several northern European countries, such as Denmark, the United Kingdom and the Netherlands.18–20 Oral and pharyngeal cancer mortality is comparatively low in European women, though trends have been rising over the last decades, and rates in some countries (Hungary in particular, but also Denmark and Romania) have reached relatively high levels, especially in middle age, reflecting drinking and smoking patterns by women in those populations. Across European countries, there was still an over 10-fold variation in male oral and pharyngeal mortality between the highest rates in Hungary (21.1/100,000) and Slovakia (16.9/100,000), and the lowest ones in Greece (1.8/100,000) and Sweden (2.2/100,000).

The diverging trends in the two sexes essentially reflect different patterns in tobacco smoking and alcohol drinking. The favourable trends in male mortality rates reflect the fall in tobacco consumption in men from most (western) European countries over the last few decades. A favourable effect of stopping smoking is in fact evident already within few years after smoking cessation,21 while the risk may remain persistently high for several years after stopping drinking.22 Conversely, tobacco consumption has increased in women in several countries,23, 24 and this has led to unfavourable oral and pharyngeal cancer mortality trends.

Oral and pharyngeal cancer mortality trends and geographic patterns also appear to be related to changes in alcohol consumption.25 The exceedingly high rates in Hungary and in a few other countries of central and eastern Europe (Slovakia, Moldova, Lithuania, Croatia, Romania) can be related to the overall quantity of alcohol consumed, but also to the drinking pattern (out of meals, binge) and to the type of alcohol consumed. In these countries, a substantial proportion of alcohol derives from fruit (plums, peaches, apricots), and home-made alcoholic beverages are widespread.8, 26–28 These may include high levels of acetaldehyde, which is an established human carcinogen.29

Age and cohort-specific analyses appear to reflect available information on the prevalence of tobacco smoking in subsequent generations of men from major European countries,30 as well as possibly the patterns of alcohol drinking, though generation specific data on alcohol consumption are not available for most countries.

The role of other factors on oral and pharyngeal cancer mortality in Europe is likely smaller than that of tobacco and alcohol, and remains largely unquantified. Some aspects of diet may influence oral and pharyngeal cancer mortality.31 Low consumption of vegetables and fruit has been related to oral and pharyngeal cancer risk32–34 and may account for a non-negligible fraction of this neoplasms in some European countries. In an Italian study, low consumption of β-carotene—considered an indicator of fruit and vegetable intake—accounted for 24% of oral and pharyngeal cancer.35

It is unlikely that trends in oral and pharyngeal cancer in Europe have been appreciably influenced by changes in diagnosis and improved certification of the disease, as oral and pharyngeal cancer is relatively easy to diagnose, and no major change in certification of this neoplasm across the subsequent ICD revisions considered in the present analysis has been introduced.

Incidence data are not available for most European countries on a national level. Some estimates have been proposed for selected countries over the last decade.3 These are broadly consistent with mortality trends, as they show increases for men in United Kingdom and the Czech Republic and declines in France, Italy and Spain. This is not surprising since, although treatment strategies have changed, 5-year survival has only moderately improved in the last decades (with a 5-year survival around 45%).3, 36–38 Thus, it is unlikely that early diagnosis and disease management have played a major role in determining the observed trends.

Though oral and pharyngeal mortality in Europe has declined in the last decade in men, there were still rises in a few central and eastern European countries, reaching exceedingly high rates in Hungary and Slovakia, which now have the highest rates on a European scale. The control of oral and pharyngeal cancer, as well as of other alcohol- and tobacco-related cancers remain, therefore, a major public health problem in those areas of the continent.39, 40

Acknowledgements

The authors thank Mrs I. Garimoldi for editorial assistance.

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