Global mesothelioma epidemic: Trend and features.

BACKGROUND: Mesothelioma incidence has taken epidemic proportions in various countries. The trend of the epidemic remains undefined.
OBJECTIVE: To collect the most recent available data on mesothelioma incidence in order to determine the present trend of the epidemic.
MATERIALS AND METHODS: Data of the Cancer and Mesothelioma Registries have been reviewed. In addition, numerous researchers were contacted to obtain supplementary information.
RESULTS: The highest incidence rates are reported from some countries in Europe (United Kingdom, The Netherlands, Malta, Belgium), and in Oceania (Australia, New Zealand). Relatively low incidence/mortality rates are reported from Japan and from Central Europe. In many countries a trend to increase continues to be observed. Data are not available for the mostly populous countries.
CONCLUSION: Mesothelioma epidemic does not show signs of attenuation. The lack of data for a large majority of the world does not allow that the consciousness of the risks related to asbestos exposure is reached.

INTRODUCTION

Asbestos has been banned in 55 countries.[1] The inhabitants of such countries (about 1,110,000,000) correspond to 16% of the world population. This means that asbestos use continues in a large part of the world. In this context it would be opportune that data on the incidence of malignant mesothelioma, a sentinel event indicating the effects of asbestos exposure, are available. However, the mesothelioma geography at a global level is poorly known.[2345678] In fact, data on mesothelioma incidence/mortality are lacking for a large majority of the world population.

In the present study the available data on mesothelioma incidence in the last years have been reviewed, in order to delineate the trend of mesothelioma epidemic.

Countries at high incidence

The highest mesothelioma incidence rates are reported from some countries in Europe (UK, The Netherlands, Malta, Belgium) and in Oceania (Australia, New Zealand).

The UK has a long tradition of studies on mesothelioma. Mesothelioma mortality has been monitored in Great Britain since 1968. The annual number of deaths from mesothelioma progressively increased, being 153 in 1968 and 2,360 in 2010. In 2011 the numbers of deaths was 2,291.[9] In the period 2000-2011 the age-standardized incidence rates (world population) (ASIR W) in the UK were 3.3-3.6 per 100,000 among men, and 0.5-0.7 among women [Figure 1].[10]

Figure 1

Mesothelioma in the UK. Age-standardized (world) incidence rates per 100,000, 2000-2011

In Australia, the annual number of mesothelioma cases progressively increased passing from 156 in 1982 to 666 in 2009.[11] ASIR (W) in 2011 were 3.2 per 100,000 among men and 0.7 among women. Mesothelioma incidence rates in Australia in the period 1982-2010 are reported in Figure 2. The Figure 3 shows a comparison of the incidence rates among men in the UK and Australia.

Figure 2

Mesothelioma in Australia. Age-standardized (world) incidence rates per 100,000, 1982-2010

Figure 3

Mesothelioma in Australia and in the UK. Age-standardized (world) incidence rates per 100,000, men, 2000-2011

In The Netherlands the mean annual number of mesotheliomas registered in the period 2008-2011 was 526.[12] In 2011 the ASIR (W) were 2.85 per 100,000 among men, and 0.35 among women.

In New Zealand the number of cases registered in the period 2000-2010 ranged between 60 and 102. The ASIR (W) among men were 3.2 per 100,000 in the period 2005-2006, and 2.5 in the period 2009-2010. In 2010 the incidence rates were 2.5 per 100,000 among men, and 0.3 among women.[13]

In Belgium, 273 mesotheliomas were registered in 2011 (223 men, and 50 women). The ASIR (W) were 2.0 per 100,000 among men, and 0.4 among women.[14]

High incidence rates were observed also in the Republic of Malta (about 400,000 inhabitants). In the biennium 2005-2006 the ASIR (W) among men was higher than 3 per 100,000; wide fluctuations were seen in the following years with values of 2.20 in 2009 and of 1.06 in 2012. Among women the rates ranged between 0.0 and 0.62.[15]

Countries with intermediate incidence rates

A second group of countries includes a large part of Europe, and the United States.

In Denmark, a Cancer Registry is active since 1943. Among men the ASIR (W) has progressively increased in the period 1943-2009, reaching a maximum in the biennium 2008-2009 with a rate of 1.76 per 100,000.[16] Among women the incidence rate remained relatively stable with a maximum of 0.5 per 100,000 in the quinquennium 1973-1977.[16]

In Finland, the ASIR (W) among men was 0.2 per 100,000 in the quiquennium 1966-1970, progressively raised in the following decades reaching the value of 1.4 in the period 1996-2000 and the value of 1.5 in the period 2001-2012 [Figure 4].[17] Among women the incidence rate was 0.1 in the decade 1966-1975; in the period 1976-2000 the rate ranged between 0.3 and 0.5 and was 0.3 in the period 2001-2012.[17]

Figure 4

Mesothelioma in Finland. Age-standardized (world) incidence rates per 100,000 men, 1966-2012

In Norway, the ASIR (W) among men was 0.1 per 100,000 in the quinquennium 1963-1967, 1.6 in the quinquennium 2003-2007, and 1.4 in the quinquennium 2008-2012 [Figure 5].[18] Among women the ASIR (W) ranged between 0.0 and 0.2 in the period 1963-2007; in the period 2008-2012 the rate was 0.3.

Figure 5

Mesothelioma in Norway. Age-standardized (world) incidence rates per 100,000 men, 1963-2012

In Sweden, mesothelioma incidence showed fluctuations in the period 2000-2011. The ASIR (W) (including malignant synovialoma) among men reached a maximum of 1.55 per 100,000 in 2002 and a minimum of 0.97 in 2008. The rate was 1.11 in 2011, and 1.34 in 2012.[19] Among women the ASIR (W) in the period 2000-2011 ranged between a minimum of 0.23 in 2005 and a maximum of 0.51 in 2004; the rate was 0.29 in 2010 and 0.38 in 2012.

In Iceland, the ASIR (W) of pleural cancer in the period 2007-2011 were 0.9 among men and 0.2 among women.[20]

In Germany, the number of mesothelioma cases registered in 2010 amounted to 1673 (1320 men and 353 women). Mesothelioma incidence remained stable in the period 2000-2010. Among men the ASIR (W) was 1.8 per 100,000 in 2000, and 1.4-1.5 in the following years.[21] Among women the rate was 0.5 in 2000, and 0.3 in the following period.[21]

In France, after the data of the Mesothelioma Surveillance National Program the mean annual number of cases in the period 1998-2010 was 675 among men; among women the number of cases ranged between 200 and 370.[22] The data corresponded to a crude incidence among men of 2.3 per 100,000.

In Italy, after the data collected by the National Mesothelioma Registry, in 2008 the ASIR (on Italian population) among men was 3.55 per 100,000 for pleural mesothelioma and 0.24 for peritoneal mesothelioma;[23] among women the rates were 1.35 and 0.12, respectively.

In Croatia, the ASIR (W) in the period 2001-2011 ranged between 1.17 and 1.84 per 100,000 among men, and between 0.20 and 0.44 among women.[24] The highest rates were reached in 2009 for men and in 2010 for women.

In Austria, the ASIR (W) in the period 2003-2011 were around 1 per 100,000 among men (1.2 in 2009), and 0.3-0.4 among women.[25]

In Cyprus, the ASIR (W) among men showed marked variations in the period 1998-2009 with a minimum of 0.1 per 100,000 and a maximum of 1.9 (in 2006). In the biennium 2008-2009 the rate was 1.4. Among women the rate ranged between 0.1 and 0.6.[26]

Mesothelioma incidence in the United States has been the object of a recent study.[27] In the period 2003-2008 over 3000 cases were diagnosed each year, with a maximum of 3284 in 2005. In this period the mean ASIR (on US population) was 1.93 per 100,000 among men, and 0.41 among women.

In Israel, the ASIR (W) in the period 2000-2010 among Jews men ranged between 0.41 and 1.23 per 100,000, being higher than 1 in 2003 and in 2008.[28] In the same period, among the Jewish women the rates ranged between 0.14 and 0.31.

In South Africa the number of mesotheliomas diagnosed histologically in 2004 amounted to 180 cases (147 in men and 33 in women). The ASIR (W) were 1.07 per 100,000 among men, and 0.18 among women.[29]

Countries with low incidence rates and/or insufficient data

Low incidence/mortality rates are reported from various countries of Central Europe, Ireland, Spain, and from several countries of Asia.

In Poland, the ASIR among men was 0.3 per 100,000 in the period 1999-2001, 0.4 in the following biennium, and 0.5-0.6 in the following years [Figure 6].[30] In the same period the rate among women ranged between 0.1 and 0.3.

Figure 6

Mesothelioma in Poland, men. Age-standardized (world) incidence rates per 100,000, 1999-2011

In Estonia, 166 mesothelioma cases were registered in the period 1968-2004 (89 in men, and 26 in women).[31] In addition it has been reported that 21 cases were registered in the period 2003-2007 with ASIR of 0.3 per 100,000 among men, and 0.1 among women.[3]

Low incidence rates have also been reported from Lithuania[3] and Albania.[3]

In Slovakia, 79 cases of malignant mesothelioma were registered in the period 2005-2008 (50 in men, and 29 in women).[32333435]

In Ireland, 337 cases of malignant pleural mesothelioma were registered in the period 1994-2009, with 87.6% involving men.[36] Mean annual ASIR (on the European population) were 0.5 per 100,000 in the period 1994-1997, and 0.7 in the period 2006-2009. In 2011 34 cases have been registered (28 in men, and 6 in women), with ASIR (W) of 0.8 per 100,000 among men, and 0.2 among women.[37]

Mortality data from pleural cancer in Spain were recently reported by Lopez Abente et al.[38] In the period 1975-2010, 6037 deaths were registered. Mortality rate among men, age-standardized on the European population, was 0.6 per 100,000 both in the quiquennium 2001-2005 as well as in the quinquennium 2006-2010. In the same periods mortality rates among women were 0.2 per 100,000.

In Japan, the number of deaths from mesothelioma increased from 500 in 1995 to 1,400 in 2012 [Figure 7].[39] The increase involved mainly men, while a smaller increase has been observed among women (from 144 in 1995 to 272 in 2012).

Figure 7

Mesothelioma in Japan. No. of deaths in the period 1995-2012

In Lebanon, in the period 2004-2008 the ASIR (W) among men ranged between 0.3 and 0.6 per 100,000.[40] Among women it ranged between 0.0 and 0.1.

In Jordan, the number of registered mesotheliomas is extremely low, with two cases reported in 2009, and six cases registered in 2010.[4142]

Asbestos-related diseases in China have been the object of a recent review.[43] Data on mesothelioma incidence at a national level are not available. The number of Cancer Registries in China has markedly increased in the last years.[4445] However, it has been estimated that in 2011 Cancer Registries covered only 13% of the population.[46]

Low mesothelioma incidences are reported from South Korea, Taiwan, Hong Kong, and Singapore.[7]

In India, 25 population-based cancer registries are active, covering 7.45% of the population. Mesothelioma cases have been reported only in four of such Registries with ASIR (W) of 0.05-0.08 per 100,000 among men and 0.05-0.1 among women.[47]

In Thailand, one of the major importers and users of asbestos, only sporadic cases of mesothelioma have been reported.[48]

In the Middle East the Gulf Center for Cancer Registration provides data on the cancer incidence in six countries (Bahrain, Kuweit, Oman, Qatar, Saudi Arabia, and United Arab Emirates), whose population amounts to about 33 million people. In the period 1998-2007, 144 mesothelioma cases were registered with very low incidences.[49]

Data are not available for very large countries such Bangladesh, Brazil, Indonesia, Nigeria, Pakistan, and Russia.

The most recent available incidence rates among men in some countries are reported in Figure 8.

Figure 8

Mesothelioma in some countries. Age-standardized (world) incidence rates per 100,000, men

Microepidemiology

It is well known that inside a given country mesothelioma incidence shows huge variations from one area to another. Consequently, incidence rates at a national level are in some way misleading. Especially in large countries, the high incidence/mortality rates observed in small areas are hidden, when the incidence at a national level is considered. The key factor is the clustering of mesothelioma cases in very restricted areas. Generally, these areas are or have been the site of asbestos mines, or asbestos industries in which asbestos was largely employed (mainly shipyards and asbestos-cement factories). Good examples of such uneven distribution are offered by Great Britain,[50] Sweden,[51] Italy,[52] Croatia,[53] United States,[27] etc. In Italy the difference in mortality rates from pleural cancer among men from one Province to another in the period 1988-1997 reached the value of 40 folds.[52]

Reliability of the data

The reliability of epidemiological data about mesothelioma is reduced by various factors. Firstly, the diagnosis of this tumor may be very difficult. A diagnosis of certainty must be based on histological examination. Also, the histological diagnosis remains often difficult, as recent reviews have emphasized.[545556] Malignant mesothelioma is proteiform and the alternative diagnoses include from one side flogistic-reactive processes and from the other various other types of neoplasia. Immunohistochemical reactions are useful in distinguishing between epithelial mesothelioma and carcinoma metastasis; for sarcomatoid mesothelioma the relevance of immunohistochemical findings is markedly reduced, since the mesothelial markers are often negative. Beside the well-known histological types of mesothelioma, a rare variety has recently been described, that may simulate both radiologically and histologically an interstitial pneumopathy or other pathological lesions.[57]

Relevant elements to confirm or to exclude the diagnosis of mesothelioma may come from the necropsy. Moreover, necropsy may reveal mesotheliomas that clinically have not been suspected or not demonstrated. However, necropsy practice showed a dramatic decline in the last decades;[58] probably this fact has serious effects on the knowledge of mesothelioma.[1659] Problems may also arise in the mesothelioma registration; for instance an inadequate registration of the death causes has been detected in the past in Japan.[60]

Finally, an important point to consider is the age classes in which the highest mesothelioma incidences occur. After the study of Henley et al.[27] on the mesothelioma incidence in the United States, mean annual incidence rate among men in the period 2003-2008 was 8.34 per 100,000 in the age class 65-74, but reached the value of 17.07 in the class 75-84, and 17.62 in the class 85 and more. In Australia, the incidence rate among men in 2008 was 40.1 in the age class 75-79, 46.0 in the class 80-84, and 50.0 in the class 85 and more.[11] When the patient is old or very old, the examinations that are conducted are more reduced and this reflects on the diagnosis reliability.

It is probable that the difficulties before quoted induced an underestimation of mesothelioma incidence.

The low mesothelioma incidence/mortality in some countries like Japan or Poland have already been object of different interpretations and discussion.[7616263] The relatively low mortality from mesothelioma registered in Japan does not agree with the fact that this country was one of the most important shipbuilders in the world, particularly in the second half of the XX century, but also in the first half of the same century. Also the low incidence rates registered in Poland does not seem to agree with the high shipbuilding activity of the country. The low mortality from mesothelioma in Spain[38] is also difficult to interpret and seems to be in contrast with the fact that this country showed a marked increase in shipbuilding activity in the second half of the XX century. In this period the production passed from 51,000 tons in 1955 to 830,000 in 1971, and the annual number of ships passed from 23 to 161.[64]

CONCLUSIONS

The most recent data available on mesothelioma epidemiology show that in many countries the incidence of the tumor does not present signs of attenuation. On the basis of global asbestos consumption in the last decades, one may predict that a further mesothelioma wave will involve large geographic areas. These are exactly the same for which data are not at present available. This lack of data does not allow that an adequate consciousness of the risk is obtained. The epidemic of asbestos-related diseases in general and of mesothelioma in particular requires that the problem is faced in a more incisive way by health international institutions.