IJC

International Journal of Cancer

Thyroid cancer mortality and incidence: A global overview

Carlo La Vecchia1, Matteo Malvezzi2, Cristina Bosetti2, Werner Garavello3, Paola Bertuccio2, Fabio Levi4 and Eva Negri2
1
Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, Milan, Italy
2
Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
3
Clinica Otorinolaringoiatrica, Department of Surgery and Translational Medicine, Universit
a degli Studi di Milano Bicocca, Milan, Italy
4
Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland

In most areas of the world, thyroid cancer incidence has been appreciably increasing over the last few decades, whereas mortal-
ity has steadily declined. We updated global trends in thyroid cancer mortality and incidence using official mortality data from
the World Health Organization (1970–2012) and incidence data from the Cancer Incidence in Five Continents (1960–2007). Male
mortality declined in all the major countries considered, with annual percent changes around 22/23% over the last decades.
Only in the United States mortality declined up to the mid 1980s and increased thereafter. Similarly, in women mortality declined
in most countries considered, with APCs around 22/25% over the last decades, with the exception of the UK, the United States
and Australia, where mortality has been declining up to the late 1980s/late 1990s to level off (or increase) thereafter. In 2008–
2012, most countries had mortality rates (age-standardized, world population) between 0.20 and 0.40/100,000 men and 0.20
and 0.60/100,000 women, the highest rates being in Latvia, Hungary, the Republic of Moldova and Israel (over 0.40/100,000)
for men and in Ecuador, Colombia and Israel (over 0.60/100,000) for women. In most countries, a steady increase in the inci-
dence of thyroid cancer (mainly papillary carcinomas) was observed in both sexes. The declines in thyroid cancer mortality reflect
both variations in risk factor exposure and changes in the diagnosis and treatment of the disease, while the increases in the inci-
dence are likely due to the increase in the detection of this neoplasm over the last few decades.

About 230,000 new cases of thyroid cancer were estimated in
2012 among women and 70,000 among men, with an age-
standardized (world population) rate of 6.10/100,000 women
and 1.90/100,000 men.1 International comparisons are com-
plex due to differences in diagnosis and ascertainment of the
disease. In any case, there is an over tenfold difference in
incidence across different parts of the world in women, high-
incidence areas (over 10/100,000 women) including selected
countries of South and North America, Italy in Europe, Japan
but relatively smaller in men.1 Incidence rates are more than
twofold higher in high-income countries as compared to low/
middle-income ones both in women (11.10/100,000 and 4.70/
100,000, respectively) and in men (3.60/100,000 and 1.40/
100,000, respectively). Globally in 2012, estimated numbers
of deaths from thyroid cancer were 27,000 in women and
13,000 in men, corresponding to mortality rates of approxi-
mately 0.6/100,000 women and 0.3/100,000 men.
In most countries, incidence rates have been appreciably
increasing over the last few decades,2,3 and if recent trends

and the Pacific Islands; the absolute variation is substantial,
Key words: incidence, joinpoint analysis, mortality, thyroid cancer,
trends
Abbreviations: APC: annual percent change; EU: European
Union; ICD: International Classification of Diseases; WHO: World
Health Organization
Additional Supporting Information may be found in the online
version of this article.
Grant sponsor: Italian Association for Cancer Research (AIRC);
Grant number: 10264; Grant sponsor: Swiss Leagues Against
Cancer; Grant sponsor: Swiss Foundation for Research Against
Cancer (KFS); Grant number: 2437-08-2009
DOI: 10.1002/ijc.29251
History: Received 1 Aug 2014; Accepted 30 Sep 2014; Online 4 Oct
2014
Correspondence to: Cristina Bosetti, Department of Epidemiology,
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via Giu-
seppe La Masa 19-20156 Milan, Italy, Tel.: 139-0239014526, Fax:
139–0233200231, E-mail: cristina.bosetti@marionegri.it
Epidemiology
are maintained, thyroid cancer may become the fourth most
common cancer by 2030 in the United States.4 Such an
increase is likely due to improved ascertainment, diagnosis
and certification, and largely or totally reflects overdiagnosis
of indolent disease, i.e., small papillary carcinomas.2,3,5 Con-
versely, mortality rates have been steadily declining in most
areas of the world,6–8 likely due to improved diagnosis, man-
agement and treatment of the disease. Survival, particularly
for papillary carcinoma (i.e., the most frequent histotype in
(young) women) is in fact extremely good (over 98% five-
year survival rate in Europe or North America), resulting in
comparatively low mortality rates.
In order to provide an updated overview of trends in
mortality from thyroid cancer in European countries and
selected other areas of the world, we have analyzed death cer-
tification data over the period 1970–2012. For a few larger
countries with long-term cancer registration data, we have
also analyzed trends in incidence by major histotypes over
the period 1960–2007.

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 2188
What’s new?
Trends in thyroid cancer incidence and mortality vary widely by country, but for most areas of the world, the data indicate an
upward trend in incidence and a downward trend in mortality. Those trends are supported by the present analysis of thyroid
cancer mortality and incidence globally. The analyses are based on data maintained by the World Health Organization (1970–
2012) and Cancer Incidence in Five Continents (1960–2007). The authors attribute the rise in thyroid cancer incidence to
increased detection of the disease and the decline in mortality to changes in diagnosis, treatment, and risk factor exposure.
Material and Methods
Mortality
Official data for thyroid cancer mortality in 28 European
countries and in 20 countries from other areas of the world
were derived from the World Health Organization (WHO)
online database, for the period 1970–2012.9 We did not con-
sider a few former Soviet Union countries (i.e., Armenia,
Azerbaijan, Georgia, Kazakhstan, Kyrgyzstan and Uzbekistan)
which had low national death certification coverage and com-
pleteness; Albania, Belarus, the Russian Federation and
Ukraine, which had no recent data; and a few other Euro-
pean countries (i.e., Iceland, Malta and Luxemburg) which
had a limited number of deaths (<10 per year in the two
sexes combined). In the American continent, 13 countries
with satisfactory death certification coverage and complete-
ness were included (i.e., Canada, the United States, Argen-
tina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador,
Mexico, Puerto Rico, Uruguay and Venezuela). Mortality
data from thyroid cancer were also available for five Asian
countries (i.e., Hong Kong, Israel, Japan, the Republic of
Korea and Singapore) and for Australia and New Zealand.
Since three different Revisions of the International Classi-
fication of Diseases (ICD) were used in the period consid-
ered, we extracted, as applicable, those corresponding to the
codes ICD-8 193,10 ICD-9 19311 and ICD-10 C73.12
Epidemiology
For most countries, population figures based on official
censuses were obtained from the same WHO database9; only
for a few countries of the Americas, population data were
retrieved from the Pan American Health Organization
(PAHO) database.13,14
We computed country- and sex-specific mortality rates
for each 5-year age group and calendar period and derived
age-standardized rates by the direct method, using the world
standard population, at all ages and truncated at 35–64
years (i.e., a widely adopted definition of middle-age popula-
tion15). For the European Union (EU) as a whole, rates
were computed using the aggregated number of deaths in
its 28 member states as defined in June 2014, and the cor-
responding populations; Cyprus was excluded as mortality
data were available for a limited number of (recent) years
only. Interpolation of missing data was only made for the
construction of the overall EU rates; when data were not
available for a country, the nearest available figures (i.e.,
generally those of the previous or subsequent year) were
replicated.
Thyroid cancer mortality and incidence
In order to identify significant changes in mortality trends
for selected countries worldwide, we performed joinpoint
regression analysis allowing for up to three joinpoints.16 For
each of the identified trends, we computed the estimated
annual percent change (APC) by fitting a regression line to
the natural logarithm of the rates using calendar year as a
regression variable. We also calculated the average APC,
based on an underlying joinpoint model estimated as the
geometric weighted average of the APCs, with the weights
equal to the lengths of each time interval segment.17
Incidence
Incidence data for thyroid cancer overall and by major histo-
logical types (i.e., follicular and papillary carcinoma) were
obtained from the Cancer Incidence in Five Continents data-
base18 over the period 1960–2007. For countries with more
than one cancer registry, data were aggregated to ensure the
highest geographic coverage, and the analyses were restricted
to the longest common calendar period between registries.
The following countries and registries were considered: Den-
mark (1978–2007); France (1988–2007): Bas-Rhin, Calvados,
Doubs, Haut-Rhin, Herault, Isere, Somme, Tam; Germany
(1970–2007): Saarland; Italy (1993–2007): Ferrara province,
Varese province, Modena, Parma, Ragusa province, Romagna,
Sassari province, Torino; the Netherlands (1989–2007); Spain
(1993–2007): Albacete, Cuenca, Girona, Granada, Murcia,
Navarra, Tarrangona; the UK (1988–2007): East of England
region, Birmingham and West Midlands, Merseyside and
Cheshire, England North Western, Oxford, England South
and Western regions, Yorkshire; United States (1975–2007):
SEER 9 registries; Hong Kong (1983–2007); Israel (1963–
2007): Jews; Japan (1978–2007): Miyagi prefecture, Osaka
prefecture; Australia (1983–2007): New South Wales, Queens-
land, Tasmania, Victoria, South Australia, West Australia).
Three-year moving averages were used to represent the his-
tology- and sex-specific incidence trends in age-standardized
incidence rates (direct method, world standard population).
Results
Table 1 gives the overall age-standardized mortality rates
from thyroid cancer in men and women in 28 European
countries, the EU as a whole, and other selected areas of
the world around 2000 (1998–2002) and 2010 (2008–2012),
with corresponding percent changes. In 2000, most coun-
tries had mortality rates between 0.20 and 0.40/100,000 in
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La Vecchia et al. 2189

Table 1. Age-adjusted (world population) death rates from thyroid cancer at all ages around 2000 (1998–2002) and around 2010 (2008–
2012) in 48 countries worldwide plus the European Union, with corresponding percent changes
Men Women
No. of No. of
deaths % Change deaths % Change
Country 2000 2010 (2010) 2010/2000 2000 2010 (2010) 2010/2000
Europe
Austria 0.52 0.39 29 225.93 0.61 0.32 43 247.33
Belgium 0.32 0.30 33 25.64 0.51 0.32 48 237.43
Bulgaria 0.36 0.32 21 213.13 0.47 0.33 33 229.30
Croatia 0.40 0.35 13 212.77 0.49 0.39 24 220.51
Czech Republic 0.42 0.33 30 220.86 0.61 0.32 47 247.87
Denmark 0.32 0.26 13 218.74 0.38 0.27 21 228.09
Estonia –1 –1 – – 0.66 0.49 13 225.61
Finland 0.41 0.34 19 214.99 0.42 0.35 32 215.55
France 0.31 0.25 144 218.54 0.35 0.25 249 229.64
Germany 0.44 0.33 296 224.64 0.48 0.31 419 236.03
Greece 0.25 0.22 29 211.04 0.25 0.28 48 13.30
Hungary 0.55 0.43 34 221.83 0.57 0.42 57 226.96
Ireland 0.28 0.28 9 21.20 0.40 0.31 12 223.64
Italy 0.40 0.35 224 212.19 0.46 0.36 347 221.88
Latvia 0.40 0.51 8 26.18 0.89 0.59 20 233.67
Lithuania 0.55 0.39 8 229.54 0.69 0.42 21 239.06
Netherlands 0.28 0.23 35 219.06 0.35 0.32 69 28.64
Norway 0.34 0.29 14 214.83 0.45 0.26 19 241.07
Poland 0.33 0.27 77 217.52 0.56 0.38 181 231.35
Portugal 0.28 0.32 32 15.71 0.40 0.37 62 27.47
Republic of Moldova 0.28 0.42 8 49.91 0.53 0.52 13 21.77
Romania 0.33 0.30 52 26.52 0.43 0.43 102 20.11
Slovakia 0.38 0.32 12 215.36 0.50 0.38 22 225.22
Slovenia 0.49 0.38 6 222.20 0.43 0.19 7 256.13

Epidemiology
Spain 0.28 0.26 109 26.68 0.34 0.30 195 210.70
Sweden 0.30 0.31 31 5.23 0.33 0.30 44 27.56
Switzerland 0.36 0.30 23 217.81 0.45 0.27 35 241.28
United Kingdom 0.21 0.22 136 4.80 0.28 0.25 209 210.63
European Union 0.34 0.30 1381 213.69 0.43 0.32 2333 223.82
America
Argentina 0.25 0.23 58 28.46 0.35 0.30 113 213.23
Brazil 0.19 0.20 196 4.42 0.33 0.29 390 212.54
Canada 0.22 0.20 72 28.47 0.21 0.18 102 214.69
Chile 0.33 0.24 26 228.25 0.55 0.52 73 26.39
Colombia 0.34 0.32 65 27.42 0.54 0.64 168 17.77
Costa Rica 0.15 0.24 6 66.89 0.57 0.32 9 243.94
Cuba 0.19 0.20 23 4.73 0.38 0.35 40 26.90
Ecuador 0.27 0.37 29 36.34 0.65 0.77 72 17.77
Mexico 0.32 0.33 161 2.23 0.62 0.59 395 24.42
Puerto Rico –1 –1 – – 0.19 0.15 10 223.87

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 2190 Thyroid cancer mortality and incidence

Table 1. Age-adjusted (world population) death rates from thyroid cancer at all ages around 2000 (1998–2002) and around 2010 (2008–
2012) in 48 countries worldwide plus the European Union, with corresponding percent changes (Continued)
Men Women
No. of No. of
deaths % Change deaths % Change
Country 2000 2010 (2010) 2010/2000 2000 2010 (2010) 2010/2000
United States 0.23 0.25 713 8.09 0.23 0.24 967 6.76
Uruguay 0.24 0.36 8 47.94 0.35 0.24 11 230.77
Venezuela 0.25 0.23 33 25.05 0.41 0.42 67 3.45
Asia
Hong Kong 0.30 0.31 19 4.59 0.43 0.29 23 231.37
Israel 0.46 0.42 20 29.04 0.64 0.62 39 23.30
Japan 0.33 0.31 533 26.08 0.47 0.39 1066 215.97
Republic of Korea 0.38 0.35 107 27.04 0.59 0.54 254 29.46
Singapore 0.38 0.27 6 229.30 0.76 0.56 17 226.80
Oceania
Australia 0.26 0.23 44 211.36 0.27 0.30 72 14.00
New Zealand 0.26 0.30 10 14.54 0.33 0.29 13 213.21
1
Rates were not reported, since there were five or less deaths.
Epidemiology

Figure 1. Age-standardized (world population) death rates from thyroid cancer at all ages per 100,000 men and women in 48 countries
worldwide plus the European Union, 2008–2012.

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La Vecchia et al.
Figure 2. Trends in age-standardized (world population) death rates from thyroid cancer per 100,000 men (all ages and age 35–64 years)
in selected countries worldwide, 1970–2012. All ages
men and between 0.20 and 0.60/100,000 in women. Male
rates were 0.34/100,000 in the EU, 0.23/100,000 in the
United States and 0.33/100,000 in Japan; corresponding fig-
ures in women were 0.43, 0.23 and 0.47/100,000, respec-
tively. Between 2000 and 2010, mortality declined in several
countries worldwide, particularly in women. Some increases
were, however, observed in Estonia, Latvia, Portugal, Mol-
dova, Sweden, the UK, most countries of the Americas
including the United States, Hong Kong and New Zealand
for men and in Greece, Colombia, Ecuador, the United
States, Venezuela and Australia for women. In 2010, most
countries still had mortality rates between 0.20 and 0.40/
100,000 men and 0.20 and 0.60/100,000 women (Table 1
and Fig. 1). The highest mortality rates were in Latvia,
Hungary, the Republic of Moldova and Israel (over 0.40/
100,000) for men and in Ecuador, Colombia and Israel
(over 0.60/100,000) for women; the lowest ones were in
Cuba, Canada, Brazil and Puerto Rico (0.20/100,000) for
men and Slovenia, Canada and Puerto Rico (below 0.20/
100,000) for women. In the EU, the United States and
Japan, rates in 2010 were 0.30, 0.25 and 0.31/100,000 men
and 0.32, 0.24 and 0.39/100,000 women, respectively.
Int. J. Cancer: 136, 2187–2195 (2015) V
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2191
; truncated at 35–64 years .
Geographic patterns and time trends between 2000 and
2010 in middle-age population (35–64 years) were consistent
Epidemiology
with all ages ones (Supporting information Table 1 and Sup-
porting information Fig. 1).
Figure 2 and Supporting information Table 2 show the
results for the joinpoint analysis of age-standardized mortal-
ity rates from thyroid cancer (at all ages and at age 35–64)
in men from 11 countries worldwide and the EU as a
whole between 1970 and 2012. Trends in male overall mor-
tality have been declining in most countries considered,
with APC around 22/23% over the last decades. Only in
Spain, mortality has been increasing up to the early 1990s
to level off thereafter, while in the United States mortality
has been declining up to the mid 1980s and has been mod-
erately increasing thereafter. Trends were consistent in
middle-aged men. Similarly, in women overall and trun-
cated mortality was declining in most countries considered,
with APCs around 22/25% over the last decades (Fig. 3
and Supporting information Table 2), with the exception
the UK, the United States and Australia, where mortality
has been declining up to the late 1980s/late 1990s to level
off (or even increase) thereafter.
 2192
Figure 3. Trends in age-standardized (world population) death rates from thyroid cancer per 100,000 women (all ages and age 35–64
years) in selected countries worldwide, 1970–2012. All ages
Trends in incidence rates for thyroid cancer overall and
for papillary and follicular carcinomas over the period 1960–
Epidemiology
2007 in selected countries worldwide are given in Figure 4
for men and Figure 5 for women. In most countries consid-
ered, a steady increase in the incidence of thyroid cancer was
observed in both men and women. Such an increase mainly
reflected the rise in the incidence of papillary carcinomas
(i.e., the most frequent histotype), while incidence for follicu-
lar carcinomas was much lower and remained approximately
stable over the period considered.
Discussion
There are three main messages in the present updated analy-
sis of thyroid cancer mortality and incidence, including: (i)
the persistent appreciable variability in thyroid cancer death
rates worldwide, most high mortality countries being in Cen-
tral America and Asia, but also central and eastern Europe,
and those with low rates in western Europe and North
America; (ii) the persistent fall in death rates for both sexes
in most previous high mortality areas, but a leveling of rates
over the last two decades in lowest mortality countries of
North America and northern Europe; and (iii) the continu-
Thyroid cancer mortality and incidence
; truncated at 35–64 years .
ous rise in the incidence of thyroid cancer over the last few
decades in various countries worldwide.
The patterns and trends in mortality from thyroid cancer
reflect both variations in risk factor exposure over geographic
areas and time periods and changes in the diagnosis and
treatment of the disease. Thus, several high mortality areas
include regions with (past) iodine deficiency or excess iodine
intake,19–22 where the frequency of benign thyroid diseases—
a major recognised risk factor for thyroid cancer23—was
high. In a pooled analysis of thyroid cancer studies world-
wide,23 goitre and benign-nodules/adenomas were the strong-
est risk factors for thyroid cancer on a population level.
Excess risks were observed for both men and women and in
relation to both papillary and follicular cancers, with relative
risks around 5. Consequently, the substantial decline in
iodine deficiency prevalence in most countries—particularly
in low and middle-income areas—may explain the favorable
trends in thyroid cancer mortality.
Other improvements in diet over the last few decades—
including a diet richer in vegetables, (micro) nutrients, flavo-
noids and other food components22—may also have contrib-
uted to the widespread thyroid cancer mortality declines.
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La Vecchia et al.
Figure 4. Trends in age-standardized (world population) incidence rates per 100,000 men for thyroid cancer overall and by major histological
types in selected countries worldwide, 1960–2007. All thyroid cancers
While it is now clear that vegetables—including cruciferous
ones—have a favorable effect on thyroid cancer,24,25 the asso-
ciations are relatively modest. The role of fish consumption
appears to be favorable in endemic goitre populations,26
thought not in coastal areas with high iodine intake. A recent
review on fish and thyroid cancer,25 however, reported no
consistent association. Likewise, findings on single nutrients,
macronutrients and vitamins are limited and inconsistent
and therefore no conclusion based on dietary patterns can be
derived to interpret mortality trends in incidence and
mortality.22
Another major risk factor for thyroid cancer is ionising
radiation, particularly in childhood and adolescence, with a
summary excess RR around 7 per Gray (Gy).27,28 It is likely
that reduced utilisation and better control of irradiation for
medical conditions, particularly in childhood, has lead to a
subsequent decline of thyroid cancer mortality.
The leveling off for low mortality rates (about 0.20/
100,000) in the United States, the UK, Australia, and other
selected European countries indicates that such a favorable
pattern in risk factor exposure and disease management is
approaching an asymptote for most frequent good prognosis
papillary cancers.
Int. J. Cancer: 136, 2187–2195 (2015) V
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2193
; papillary carcinoma and follicular carcinoma .
It is much more complex to define the risk factors for fol-
licular,29 medullary30 and anaplastic thyroid cancers, and
hence to prevent—and avoid deaths from—these thyroid can-
Epidemiology
cer subtypes. Likewise, the management and prognosis of
these histotypes of thyroid cancer are substantially less favor-
able than for papillary ones, and this may account for a back-
ground, though low, stable level of thyroid cancer mortality
observed in several low mortality areas.
In contrast to the declines in mortality from thyroid can-
cer, steady rises have been observed in the incidence of this
neoplasm (particularly of the papillary subtypes) in many
countries worldwide over the last decades. Known or likely
risk factors for thyroid cancer have not been increasing in
the last few decades, but, if any, they have been favorably
changing, as discussed above. Thus, the rise in thyroid cancer
incidence does not appear to reflect a real increase in the
occurrence of this neoplasm, but it is more likely due to a
substantial increment in the detection of subclinical thyroid
cancers (such as small papillary carcinomas) over the last
decades, particularly in young women.2,4,31 Indeed, diagnostic
techniques for thyroid cancer have become more sensitive,
particularly through the use of ultrasounds, ultrasound-
guided fine-needle aspiration and computed tomography
 2194 Thyroid cancer mortality and incidence

Figure 5. Trends in age-standardized (world population) incidence rates per 100,000 women for thyroid cancer overall and by major histological
types in selected countries worldwide, 1960–2007. All thyroid cancers ; papillary carcinoma and follicular carcinoma .

scan, which can detect thyroid nodules as small as 0.2 cm.
An important role of “overdiagnosis” is also supported by a
shift in the stage distribution of this neoplasm toward earlier
stages reported in a few US studies.2,3 This has led to a mas-
Epidemiology
Thus, the diverging trends in the incidence of and mortal-
ity from thyroid cancer, and the possible relevant role of
“overdiagnosis”, indicate the need to better distinguish the
(few) high-risk patients who necessitate treatment from those

sive overtreatment of thyroid lesions with excellent prognosis (probably most) patients who may not need treatment.
(such as small asymptomatic papillary cancers), but probably
also to a fall in mortality due to the treatment of a subgroup Acknowledgement
of lesions with unfavorable prognosis. The authors thank Mrs. I. Garimoldi for editorial assistance.

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