ORIGINAL ARTICLE

Global Incidence, Risk Factors, and Temporal

Trends of Mesothelioma: A Population-Based Study
Junjie Huang, PhD,a,b Sze Chai Chan, MSc,a Wing Sze Pang, BSocSc,a
Shui Hang Chow, MSocSc,a Veeleah Lok, MPH,c Lin Zhang, PhD,d,e Xu Lin, MD,f
Don Eliseo Lucero-Prisno III, PhD,g Wanghong Xu, PhD,h Zhi-Jie Zheng, PhD,i
Edmar Elcarte, MA,j Mellissa Withers, PhD,k Martin C. S. Wong, MD, MPH,a,b,e,i,*;
NCD Global Health Research Group, Association of Pacific Rim Universities (APRU)
a
The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong,
Hong Kong SAR, People’s Republic of China
b
Centre for Health Education and Health Promotion, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
SAR, People’s Republic of China
c
Department of Global Public Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
d
School of Population and Global Health, The University of Melbourne, Victoria, Australia
e
School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s
Republic of China
f
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou,
Zhejiang, People’s Republic of China
g
Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom
h
School of Public Health, Fudan University, Shanghai, People’s Republic of China
i
Department of Global Health, School of Public Health, Peking University, Beijing, People’s Republic of China
j
University of the Philippines, Manila, Philippines
k
Department of Population and Health Sciences, Institute for Global Health, University of Southern California, Los Angeles,
California

Received 2 December 2022; revised 30 December 2022; accepted 31 January 2023

Available online - 10 February 2023

ABSTRACT 0.161, p < 0.001), and asbestos exposure (b ¼ 0.087, CI:

0.073–0.102, p < 0.001) had higher mesothelioma. The
Introduction: Mesothelioma is an uncommon type of can-
overall trend of mesothelioma incidence was decreasing,
cer which has received little attention. This study aims to
although an increase was observed in Bulgaria (AAPC: 5.56,
evaluate the global disease burden; trends of mesothelioma
95% CI: 2.94–8.24, p ¼ 0.001) and Korea (AAPC: 3.24, 95%
by age, sex, and geographic locations; and its risk factors on
CI: 0.08–6.49, p ¼ 0.045).
the population level.
Conclusions: There was a substantial declining incidence
Methods: The Global Cancer Observatory, Cancer Incidence
trend of mesothelioma in the past decade possibly related
in Five Continents Plus, and Global Burden of Disease were
to the restriction of the use of asbestos in some countries.
accessed for mesothelioma incidence and its risk factors
Meanwhile, the increasing trend in mesothelioma incidence
worldwide. The associations between mesothelioma inci-
dence and asbestos were evaluated for each country by
multivariable linear regression analysis by sex and age.
Average annual percentage change (AAPC) was calculated *Corresponding author.
using Joinpoint regression to evaluate the epidemiologic Disclosure: The authors declare no conflict of interest.
trends of mesothelioma. Address for correspondence: Martin C.S. Wong, MD, MPH, The Jockey
Club School of Public Health and Primary Care, Faculty of Medicine,
Results: The age-standardized rate of mesothelioma was The Chinese University of Hong Kong, Room 407, 4/F, Postgraduate
Education Centre, Prince of Wales Hospital, 30-32 Ngan Shing Street,
0.30 per 100,000 persons with Northern Europe reporting Shatin, N.T., Hong Kong SAR, China. E-mail: wong_martin@cuhk.edu.hk
the highest incidence rates. The incidence rate of the male ª 2023 International Association for the Study of Lung Cancer.
population was much higher than that of the females. Published by Elsevier Inc. This is an open access article under the
CC BY license (http://creativecommons.org/licenses/by/4.0/).
Countries with higher human development index (b ¼
ISSN: 1556-0864
0.119, confidence interval [CI]: 0.073–0.166, p < 0.001),
https://doi.org/10.1016/j.jtho.2023.01.095
gross domestic product per capita (b ¼ 0.133, CI: 0.106–

Journal of Thoracic Oncology Vol. 18 No. 6: 792–802

June 2023
observed in females might be indicative of an increase in
environmental exposure to mineral fibers.
 2023 International Association for the Study of Lung
Cancer. Published by Elsevier Inc. This is an open access
article under the CC BY license (http://creativecommons.
org/licenses/by/4.0/).
Keywords: Mesothelioma; Incidence; Risk factors; Temporal
trend
Introduction
Mesothelioma is a rare cancer, accounting for merely
0.17% of the total estimated cancer cases in 2020.1,2 As
an orphan disease, mesothelioma has not attracted much
attention. There has been a lack of drugs, and conse-
quently, its survival has remained largely unaltered for
the past 50 years.3 For the 2011–2017 period, the 5-year
relative survival rate of people diagnosed with having
mesothelioma was 12%, remarkably lower than the
5-year survival rate of 62.7% for all cancers.4,5 In addi-
tion, mesothelioma has a remarkably long latency period,
which could last for 30 to 40 years generally between
the first exposure to asbestos and the onset.6,7
The major risk factor of mesothelioma is asbestos,
which can be easily found in the occupational environ-
ment.6 Though the use of asbestos was tightly restricted
or banned by many developed countries since the
1980s,6 more than half of the cases, especially in men,
were suspected to be caused by occupational exposure
to asbestos in some earlier studies.8,9 Another main
source of asbestos exposure and a main cause of meso-
thelioma is environmental exposure, which includes
household and neighborhood exposure to asbestos.10
Despite its increasing relevance to mesothelioma, using
environmental exposure to asbestos as a proxy may not
be feasible owing to the difficulty in quantifying espe-
cially when the exposure is often involuntary and un-
known.11 Nevertheless, studies have found that neither
occupational nor environmental asbestos exposure in
the United States in 2008 would be a significant risk
factor for mesothelioma,8 suggesting the presence of
unexplored potential risk factors. Evidence has revealed
other risk factors which might be associated with me-
sothelioma. For instance, heterozygous germline BAP1
pathogenic mutations,12 radiotherapy,13 ionizing radia-
tion,14 and Simian Virus 40 (SV40)15 had been associ-
ated with higher incidence of mesothelioma among
people exposed to asbestos.
Previous studies had been done to evaluate the inci-
dence trends of mesothelioma. Nevertheless, they were
limited to a single country8,16 or region17,18 or used
relatively old data.19 This study aims to fill the gap by
Global Mesothelioma Epidemiology 793
comprehensively evaluating the global disease burden
and trends of mesothelioma by region, country, sex,
and age group. Furthermore, the associations between
human development index (HDI), gross domestic product
(GDP), and occupational exposure to asbestos and meso-
thelioma incidence on a population level will be explored.
Materials and Methods
Data Sources
The Global Cancer Observatory database was used to
extract the mesothelioma incidence for 185 countries in
2020.2 The Global Cancer Observatory is an online
database that provides global statistics on 26 types of
cancer by sex and age group to support cancer preven-
tion and research. This database was produced by the
International Association of Cancer Registries through
collaborations with population-based cancer registries
and the WHO or is based on freely accessible online in-
formation. The retrieved data were used in the estima-
tion of the incidence-to-mortality ratios, prediction of
trend analysis, and approximation from neighboring
nations using international or national cancer registry
data.1 The Cancer Incidence in Five Continents Plus
database was retrieved for site-specific proportions of
mesothelioma incidence; the extracted information was
10-year cancer incidence (from 2003 to 2012) in 108
countries.20 The Cancer Incidence in Five Continents
Plus database was used for time trends analyses and to
interpret the difference over time; it contains annual
cancer incidence from more than 100 cancer registries
by various population groups including the most upda-
ted and older data possible. For risk factors analysis, the
country-specific data on asbestos exposure were
extracted from the Global Burden of Disease database.21
The Global Burden of Disease database aims to improve
health care systems and to eradicate inequities by
measuring the health burden of diseases, injuries, and
risk factors. Data about premature mortality and
disability caused by more than 350 diseases and injuries
were collected and analyzed by 7000 researchers in 156
countries and regions. The HDI and GDP per capita for
each country were taken from the United Nations and
the World Bank, respectively.22,23
Statistical Analysis
Choropleth maps were generated to illustrate the global
mesothelioma incidence using the age-standardized rates
(ASRs) for different countries by sex and age group. The ASR
is the weighted arithmetic mean of age-specific rates per
100,000 people, where the weights correspond to the ratio
of people in the Segi-Doll world reference population.24
The associations between mesothelioma incidence
and risk factors, including HDI, GDP per capita, and
794 Huang et al
occupational exposure to asbestos, were evaluated for
each country by multivariable linear regression analysis
by sex and age. Beta coefficients (b) and the corresponding
95% confidence intervals (CIs) were generated corre-
spondingly from the regression. The b estimates are the
amount of change in outcome variable (ASR of incidence)
for every unit increase in a predictor variable (risk factor).
Statistical significance was determined as a p value less
than 0.05, and all CIs are expressed at 95% value.
Joinpoint regression analysis software was adopted
to perform trend analysis, which is developed by the
Surveillance, Epidemiology, and End Results Program
under the U.S. National Cancer Institute. The temporal
trend of mesothelioma incidence was computed by the
average annual percentage change (AAPC).25 In accor-
dance with standard procedure, research on cancer
epidemiology used data from the most recent 10-year
period. The incidence data had undergone a logarith-
mic transformation, and related SEs had been calculated.
Following that, they were used to determine the AAPC
and the 95% CI for various demographic groups. The
AAPC indicates the temporal trends of mesothelioma,
with a growing trend is illustrated by a positive AAPC
and vice versa. The 95% CI was used as a tool to evaluate
the accuracy of trend estimates, for example, an interval
that overlaps with 0 denotes a stable trend without
significant increase or decrease. Furthermore, the trends
of mesothelioma incidence of different population
groups were evaluated by age groups (all population:
0–85þ y, young population: 15–49 y, old population:
50–74 y), sexes (male and female), and geographic lo-
cations (Asia, Oceania, America, Europe, and Africa).
Results
Mesothelioma Incidence in 2020
There were an estimated 30,870 mesothelioma cases
reported globally, with an ASR of 0.30 per 100,000
persons. The highest ASR was found in Northern Europe
(1.4), Australia and New Zealand (1.3), Western Europe
(0.79), Southern Europe (0.70), and Southern Africa
(0.55). In contrast, the lowest ASR was found in the
Caribbean (0.05), Eastern Africa (0.06), Western Africa
(0.06), Middle Africa (0.07), and South-Central Asia
(0.10). A 23-fold difference was found between loca-
tions. For countries, the highest incidence rate was found
in Luxembourg (4.1), United Kingdom (1.9), Australia
(1.3), The Netherlands (1.3), New Zealand (1.2), and
Belgium (1.1). The lowest incidence rate was found in
Bangladesh (0.01), Sudan (0.01), Nepal (0.01), Panama
(0.01), Chad (0.01), and Pakistan (0.02).
Mesothelioma Incidence by Subgroup in 2020
In the male population, the global incidence of me-
sothelioma as measured by the ASR was 0.46 per
Journal of Thoracic Oncology Vol. 18 No. 6
100,000 persons (21,560 cases) (Fig. 1). The female
incidence was much lower than male incidence with an
ASR of 0.17 (9310). The highest incidence in males was
found in Northern Europe (2.5), Australia and New
Zealand (2.2), and Western Europe (1.3); in females, it
was in Luxembourg (5.3 versus 3.2 in females), United
Kingdom (3.3 versus 0.59), and the Netherlands (2.3
versus 0.36). As for the young and old populations, the
ASR incidence of mesothelioma in old (1.0, 16,800) was
higher than in the young (0.06, 2241) (Fig. 2). The
highest incidence in the old was found in Northern
Europe (5.5 versus 0.05 in the young), Australia and
New Zealand (4.1 versus 0.1), and Western Europe (2.8
versus 0.08); in the young, it was in Luxembourg (15.6
versus 1.6 in the young), United Kingdom (7.3 versus
0.06), and the Netherlands (4.8 versus 0.09).
Associations of Risk Factors With Mesothelioma
Incidence
In all populations, higher HDI (b ¼ 0.119, CI: 0.073–
0.166, p < 0.001), higher GDP per capita (b ¼ 0.133, CI:
0.106–0.161, p < 0.001), and higher asbestos exposure
(b ¼ 0.087, CI: 0.073–0.102, p < 0.001; Fig. 3) were
associated with higher mesothelioma incidence. The male
subgroup was found to have higher mesothelioma inci-
dence with higher HDI (b ¼ 0.192, CI: 0.122–0.264,
p < 0.001), higher GDP per capita (b ¼ 0.208, CI: 0.166–
0.250, p < 0.001), and higher asbestos exposure (b ¼
0.088, CI: 0.077–0.100, p < 0.001). For the female sub-
group, higher mesothelioma incidence was associated
with higher HDI (b ¼ 0.062, CI: 0.022–0.102, p ¼ 0.003),
higher GDP per capita (b ¼ 0.087, CI: 0.064–0.111,
p < 0.001), and higher asbestos exposure (b ¼ 0.071, CI:
0.036–0.107, p < 0.001). A similar association was also
found in the old population. Fewer associations were
found between risk factors and mesothelioma incidence
in the young population; the risk factor was higher GDP
per capita (b ¼ 0.035, CI: 0.021–0.049, p < 0.001).
Multivariate regression has revealed that higher meso-
thelioma incidence overall was associated with higher
asbestos exposure (b ¼ 0.065, CI: 0.047–0.083, p < 0.001)
after adjusting for HDI and GDP. In subgroup analysis, such
association was found among males (b ¼ 0.072, CI: 0.057–
0.087, p < 0.001) and the older population (b ¼ 0.174, CI:
0.123–0.224, p < 0.001) only (Supplementary Table 1).
Trend Analysis of Mesothelioma Incidence
Among countries with higher HDI (0.900 or above),
the overall trend of mesothelioma incidence was
decreasing. Decreasing trends were found in Australia
(AAPC: 1.54, 95% CI: 2.26 to 0.81, p ¼ 0.001), the
USA (AAPC: 1.75, 95% CI: 2.85 to 0.65, p ¼ 0.007),
Norway (AAPC: 1.94, 95% CI: 3.52 to 0.34, p ¼
0.023), and Germany (AAPC: 4.11, 95% CI: 5.97
June 2023
Figure 1. Global incidence of mesothelioma by sex, all ages, in 2020.
to 2.21, p ¼ 0.001). In contrast, increasing trend was
only observed in Korea (AAPC: 3.24, 95% CI: 0.08–6.49,
p ¼ 0.045) (Supplementary Fig. 1, Supplementary Fig. 2,
Supplementary Table 2). Meanwhile, significant
increasing and decreasing trend was found in Bulgaria
(AAPC: 5.56, 95% CI: 2.94–8.24, p ¼ 0.001) and Brazil
(AAPC: 13.08, 95% CI: 18.73 to 7.03, p ¼ 0.001),
respectively. Other 34 countries did not have significant
increases or decreases during the period.
Age- and Sex-Specific Trend Analysis by
Subgroup
For males, among countries with higher HDI,
decreasing trends were found in six countries (Fig. 4).
Global Mesothelioma Epidemiology 795
The largest decreases were found in Germany
(AAPC: 4.13, 95% CI: 6.98 to 1.19, p ¼ 0.012),
New Zealand (AAPC: 3.86, 95% CI: 6.03, 1.65, p ¼
0.004), and Norway (AAPC: 2.93, 95%
CI: 5.14, 0.66, p ¼ 0.018). Meanwhile, no country
has reported significant increases. Among countries
with lower HDI, increasing and decreasing trends were
found in four and three countries, respectively. Notable
increases and decreases were found in Chile (AAPC:
22.64, 95% CI: 15.33–30.41, p < 0.001) and the
Philippines (AAPC: 6.99, 95% CI: 11.66 to 2.07,
p ¼ 0.006), respectively. Other 28 countries did not
have significant increases or decreases during the
period.
796 Huang et al
Figure 2. Global incidence of mesothelioma by age, both sexes, in 2020.
For females, only Korea reported a significant rise
(AAPC: 8.27, 95% CI: 0.46–16.68, p ¼ 0.040), and no
country reported significant decrease among coun-
tries with higher HDI. Among countries with lower
HDI, significant increasing trends were found in
Thailand (AAPC: 13.68, 95% CI: 2.71–25.83, p ¼
0.013), followed by Bulgaria (AAPC: 9.38, 95% CI:
2.88–16.28, p ¼ 0.010), and Martinique (AAPC: 3.58,
95% CI: 3.45–3.70, p < 0.001), whereas Brazil re-
ported a decreasing trend (AAPC: 10.64, 95%
CI: 15.38 to 5.63, p ¼ 0.001). Other 36 countries
did not have significant increases or decreases during
the period.
Journal of Thoracic Oncology Vol. 18 No. 6
In the young population aged 15 to 49 years, among
countries with higher HDI, decreasing trends were found
in five countries (Fig. 5). The greatest decreases were
found in Israel (AAPC: 14.73, 95% CI: 25.14 to 2.87,
p ¼ 0.022), Germany (AAPC: 12.77, 95% CI: 23.59
to 0.42, p ¼ 0.045), and Ireland (AAPC: 11.21, 95%
CI: 20.73 to 0.54, p ¼ 0.042). No country has reported
significant increases. Among countries with lower HDI,
decreasing trends were found in four countries, with the
most remarkable decreasing trend found in Kuwait
(AAPC: 16.47, 95% CI: 23.67 to 8.58, p < 0.001),
followed by Ecuador (AAPC: 14.21, 95% CI: 19.11
to 9.02, p < 0.001), and Bahrain (AAPC: 13.17, 95%
June 2023 Global Mesothelioma Epidemiology 797

15
5
Incidence (ASR) of Mesothelioma

Incidence (ASR) of Mesothelioma

4

10
2 3

5
0 1

0
4 6 8 10
4 6 8 10
HDI (1/10)
HDI (1/10)

15
5
Incidence (ASR) of Mesothelioma

Incidence (ASR) of Mesothelioma

4

10
2 3

5
1 0

0
0 5 10 15
0 5 10 15
GDP per capita (10000 USD)
GDP per capita (10000 USD)

15
5
Incidence (ASR) of Mesothelioma

Incidence (ASR) of Mesothelioma

4

10
2 3

5
1 0

0 10 20 30 0 10 20 30
Occupational exposure to asbestos Occupational exposure to asbestos

Men: Individual country 95% CI Fitted values Women: Individual country 95% CI Fitted values

Young: Individual country 95% CI Fitted values Old: Individual country 95% CI Fitted values

Figure 3. Associations between risk factors and mesothelioma incidence. CI, confidence interval; GDP, gross domestic
product; HDI, human development index; USD, U.S. dollar.

CI: 24.36 to 0.34, p ¼ 0.045). Meanwhile, increasing countries with lower HDI, decreasing trends were found
trends were found in Chile (AAPC: 29.84, 95% CI: 25.74– in three countries, with the most remarkable decrease
34.06, p < 0.001) and Estonia (AAPC: 26.51, 95% CI: found in Brazil (AAPC: 15.38, 95% CI: 25.59
20.27–33.07, p < 0.001). Other 30 countries did not have to 3.78, p ¼ 0.011). Conversely, significant increases
significant increases or decreases during the period. were found in three countries, as Bulgaria (AAPC: 8.59,
In the old population aged 50 to 74 years, among 95% CI: 3.31–14.14, p ¼ 0.005) had the greatest
countries with higher HDI, five countries have reported decrease. Other 29 countries did not have significant
significant decreasing trends. Germany (AAPC: 5.46, increases or decreases during the period.
95% CI: 8.10 to 2.75, p ¼ 0.002) had the greatest
decrease, followed by the USA (AAPC: 3.34, 95%
CI: 5.31 to 1.34, p ¼ 0.005) and Australia Discussion
(AAPC: 2.42, 95% CI: 3.30 to 1.53, p < 0.001). In Summary of Major Findings
contrast, Iceland (AAPC: 13.30, 95% CI: 10.44–16.24, p < This study is a multifaceted, global analysis on the
0.001) was observed with a significant increase. Among disease burden, risk factors, and trends of mesothelioma.
798 Huang et al
Figure 4. AAPC of mesothelioma incidence by sex, all ages. AAPC, average annual percentage change; HDI, human devel-
opment index.
The following are some major findings: (1) a substantial
geographic disparity in the disease burden of mesothe-
lioma was found, with higher incidence observed in
more developed regions, such as Northern Europe; (2)
higher incidence of mesothelioma was associated with
multiple factors, including higher HDI, higher GDP per
capita, and higher asbestos exposure (for all groups
except the younger population); and (3) there has been
an overall decreasing trend in incidence, particularly
among the younger age group aged 15 to 49 years.
Variation in the Disease Burden
The disease burden of mesothelioma varied sub-
stantially among different regions in 2020. The greatest
disease burden of mesothelioma was found in Northern
Europe, Australia and New Zealand, and Western
Europe. It could probably be attributable to the high past
asbestos use in these early industrialized regions.26–29
The difference might likely be an indicator of in-
equality in access to health care resources, as there has
been a substantial national disparity among the accuracy
of diagnosis. Despite an improvement in the accuracy of
diagnosis owing to novel immunohistochemical and
molecular markers, approximately 14% and 50% of
Journal of Thoracic Oncology Vol. 18 No. 6
mesothelioma diagnoses had been incorrect in higher-
resource and developing countries, respectively.30 The
risk of misdiagnosis of mesothelioma would be increased
because of limited experience in diagnosing mesotheli-
oma from most pathologists, more so in developing
countries,30 and the tendency to make a definitive
diagnosis even when there was inadequate evidence.31
A very marked difference was also found among the
two sexes, with the male population having considerably
higher incidence of mesothelioma, likely because of the
higher primary asbestos exposure level among males,29
as males was in the major proportion of the industrial
setting, such as mining, shipbuilding, and construction.13
Meanwhile, the large disparity in incidence found be-
tween the two age groups was possibly a result of the
national bans on asbestos32 and the long latency period
of mesothelioma (median time since first exposure: 38.4
y, interquartile range: 31.3–45.3 y),33,34 which led to the
lower incidence among the younger population.
Associated Risk Factors
In our study, analysis revealed that the risk of me-
sothelioma was positively and significantly associated
with HDI and GDP, which could be explained by the more
June 2023
Figure 5. AAPC of mesothelioma incidence by ages, both sexes. AAPC, average annual percentage change; HDI, human
development index.
prevalent use of asbestos in the past in the highly
developed and industrialized regions.
Asbestos has been the main risk factor of mesothe-
lioma, and the risk ratio (RR) largely depends on the
duration of exposure. Compared with patients without
occupational exposure, the RR of mesothelioma
increased from 3.9 (95% CI: 2.2–6.8) for patients with
less than 10 years of exposure each before and after age
30 years to 13.1 (95% CI: 8.9–89.3) for patients with 10
years of exposure or more each both before and after age
30 years.35 Meta-regression has revealed that the
cessation of asbestos exposure does not decrease the
risk of mesothelioma after 10 years (RR ¼ 1.02, 95% CI:
0.87–1.19).36 The effect of asbestos on the risk of me-
sothelioma would also increase with co-exposure to
other material including refractory ceramic fibers (OR ¼
1.6, 95% CI: 1.2–2.2).37
The exposure to ionizing radiation was also found to
be associated with higher risk for mesothelioma. Both
exposure to high doses for short periods (RR ¼ 3.34, 95%
CI: 1.24–8.99) and exposure to low doses for a prolonged
duration (RR ¼ 3.57, 95% CI: 2.16–5.89) increased the
risk of mesothelioma by more than threefold.14 A Dutch
study has reported a 26-fold increased risk (standardized
Global Mesothelioma Epidemiology 799
incidence ratio ¼ 25.7, 95% CI: 13.7–44.0) for mesothe-
lioma among patients after radiotherapy for treatment of
Hodgkin’s lymphoma and a much higher risk (standard-
ized incidence ratio ¼ 44.8, 95% CI: 23.2–78.3) among
patients treated with a combination of chemotherapy and
radiotherapy compared with the general population,
indicating a potential synergistic effect between radio-
therapy and chemotherapy.38 Furthermore, SV40, a pol-
yomavirus that can infect and transform human
mesothelial, was suggested to have contributed to the
immense increase in the incidence of mesothelioma.15,39–
41
A synergistic effect between SV40 and asbestos on
mesothelioma has also been identified in geographic re-
gions with higher levels of asbestos exposure and SV40-
contaminated polio vaccines.42–45
In our study, significant associations between higher
incidence of mesothelioma and asbestos exposure were
found for all groups except the young population. It
supported the findings that asbestos exposure would
become less of a factor in the future.8
Trends in Incidence
There was an overall decreasing trend in the inci-
dence of mesothelioma in highly developed countries,
800 Huang et al
such as Australia, the USA, and Germany, but a mixed
trend in other countries. The decline was likely the result
of the implementation of national policies for a total ban
on asbestos.32 Nevertheless, for many countries, there
might not be an immediate effect after the ban owing to
the long latency period. Previous studies had predicted
the incidence of mesothelioma, and the projection varied
substantially among countries: A South Korean study
predicted a continuous increase in the next 20 years
with no peak46; the incidence of mesothelioma would
not reach the peak until 2027.47 Nevertheless, in the
United Kingdom, mesothelioma cases were projected to
decrease in the period 2015–2035 (males: 1.42%,
females: 1.17% [per year on average]).48 In short, the
trends of country-specific incidence of mesothelioma
were dependent on the time of introduction of asbestos
bans.
In our study, evident decreasing trends in incidence
among the younger population were observed. It is less
likely that the mesothelioma observed in this age group
was due to occupational exposure to asbestos. It may
relate to policy outcomes on the regulation on occupa-
tional exposure to asbestos in the Western countries,
especially the USA, the government of which legalized
the first asbestos regulation in the early 1970s and a
total ban in the late 1980s.6 Younger individuals can take
less risk of asbestos exposure in the occupational or
industrial setting. Therefore, the decreasing trends might
be the result of the reduction in secondary exposure to
asbestos49 or the decline in other unknown risk factors
not related to asbestos.
Although the decreasing trend observed in males was
likely a result of the decrease in occupational exposure
to asbestos, the increasing trend in females could most
likely be ascribed to the environmental exposure to
asbestos.11 Some forms of asbestos have not been
regulated despite being classified as a group 1 carcin-
ogen by the WHO. For instance, erionite was used to
build houses, pave roads, and construct playgrounds in
Turkey and the USA.50 Nevertheless, the measurement of
environmental exposure to asbestos is challenging as it
is often involuntary and unknown.11
Strength and Limitations
This study is a comprehensive analysis on the disease
burden, risk factors, and the temporal trends of meso-
thelioma with cancer data of high quality from 186
countries. Nevertheless, there are some noteworthy lim-
itations. First, the estimated number of cases of meso-
thelioma reported globally might not be reliable,
particularly in Low- and Middle-income Countries, as
there are potential under-reporting and misclassification
of cancer cases, owing to substandard quality of cancer
Journal of Thoracic Oncology Vol. 18 No. 6
data, coverage of registry and analytical capacity, accu-
racy of diagnosis, and the long latency period of the can-
cer. Second, overestimation or underestimation of
associations might be possible owing to confounding as
the results were based largely on univariate analysis; the
results should be interpreted with caution, and possibility
of nonlinear associations between the evaluated factors
and mesothelioma should not be overlooked. Third, there
might be changes in cancer registries for some countries;
hence, direct comparison over time might not be appro-
priate. Nevertheless, findings based on the comparison
made among countries, regions, and sexes at the same
time frame should be comparatively robust.
Implications
Overall, there has been a substantial decrease in the
trends of mesothelioma, especially among highly devel-
oped countries, probably attributable to the total ban on
the use of asbestos in some countries. Nevertheless,
owing to the long latency period of mesothelioma, stable
and increasing trends were observed in some countries.
An increasing trend in mesothelioma incidence observed
in females was suggestive of a likely increase in envi-
ronmental exposure to asbestos; thus, it is important to
closely monitor its subsequent trends in various regions
to evaluate its impact on the epidemiology of mesothe-
lioma. Further studies could be done to capture the
mortality trend of mesothelioma worldwide. Further-
more, retrospective cohort study could be conducted in
the future to explore risk factors not related to occupa-
tional exposure to asbestos as environmental exposure
to mineral fibers might become the dominating risk
factor of mesothelioma.
CRediT Authorship Contribution
Statement
Junjie Huang: Conceptualization and supervision,
Writing—original draft.
Sze Chai Chan: Data curation, Formal analysis,
Writing—original draft.
Wing Sze Pang, Shui Hang Chow: Writing—original
draft.
Veeleah Lok, Lin Zhang, Xu Lin, Don Eliseo
Lucero-Prisno, III, Wanghong Xu, Zhi-Jie Zheng,
Edmar Elcarte, Mellissa Withers: Writing—review and
editing.
Martin C.S. Wong: Conceptualization, Supervision,
and Writing—review and editing.
Ethics
This study was approved by the Survey and Behav-
ioural Research Ethics Committee, The Chinese Univer-
sity of Hong Kong (number SBRE-20-332).
June 2023
Supplementary Data
Note: To access the supplementary material accompa-
nying this article, visit the online version of the Journal of
Thoracic Oncology at www.jto.org and at https://doi.
org/10.1016/j.jtho.2023.01.095.
References
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics
2020: GLOBOCAN estimates of incidence and mortality
worldwide for 36 cancers in 185 countries. CA Cancer J
Clin. 2021;71:209–249.
2. Ferlay J, Ervik M, Lam F, et al. Global cancer observa-
tory: cancer today. International Agency for Research on
Cancer. https://gco.iarc.fr/today. Accessed December
15, 2021.
3. Guazzelli A, Meysami P, Bakker E, et al. What can inde-
pendent research for mesothelioma achieve to treat this
orphan disease? Expert Opin Investig Drugs.
2019;28:719–732.
4. NIH, National Cancer Institute, About the SEER Program.
https://seer.cancer.gov/about/. Accessed November 1,
2022.
5. Gloeckler Ries LA, Reichman ME, Lewis DR, Hankey BF,
Edwards BK. Cancer survival and incidence from the
Surveillance, Epidemiology, and End Results (SEER) pro-
gram. Oncologist. 2003;8:541–552.
6. Alpert N, Gerwen MV, Taioli E. Epidemiology of meso-
thelioma in the 21st century in Europe and the United
States, 40 years after restricted/banned asbestos use.
Transl Lung Cancer Res. 2020;9(suppl 1):S28–S38.
7. Jane Henley S, Larson TC, Wu M, et al. Mesothelioma
incidence in 50 states and the District of Columbia,
United States, 2003–2008. Int J Occup Environ Health.
2013;19:1–10.
8. Price B, Ware A. Time trend of mesothelioma incidence
in the United States and projection of future cases: an
update based on SEER data for 1973 through 2005. Crit
Rev Toxicol. 2009;39:576–588.
9. Olsen NJ, Franklin PJ, Reid A, et al. Increasing incidence
of malignant mesothelioma after exposure to asbestos
during home maintenance and renovation. Med J Aust.
2011;195:271–274.
10. Bourdès V, Boffetta P, Pisani P. Environmental exposure
to asbestos and risk of pleural mesothelioma: review and
meta-analysis. Eur J Epidemiol. 2000;16:411–417.
11. Baumann F, Carbone M. Environmental risk of mesothe-
lioma in the United States: an emerging concern-
epidemiological issues. J Toxicol Environ Health B.
2016;19:231–249.
12. Carbone M, Pass HI, G, et al. Medical and surgical care of
patients with mesothelioma and their relatives carrying
germline BAP1 mutations. J Thorac Oncol. 2022;17:873–
889.
13. Zhai Z, Ruan J, Zheng Y, et al. Assessment of global
trends in the diagnosis of mesothelioma from 1990 to
2017. JAMA Netw Open. 2021;4:e2120360.
14. Visci G, Rizzello E, Zunarelli C, Violante FS, Boffetta P.
Relationship between exposure to ionizing radiation and
mesothelioma risk: a systematic review of the scientific
Global Mesothelioma Epidemiology 801
literature and meta-analysis. Cancer Med. 2022;11:778–
789.
15. Carbone M, Gazdar A, Butel JS. SV40 and human meso-
thelioma. Transl Lung Cancer Res. 2020;9(suppl 1):S47–
S59.
16. Zhao J, Zuo T, Zheng R, et al. Epidemiology and trend
analysis on malignant mesothelioma in China. Chin J
Cancer Res. 2017;29:361–368.
17. Montanaro F, Bray F, Gennaro V, et al. Pleural mesothe-
lioma incidence in Europe: evidence of some decelera-
tion in the increasing trends. Cancer Causes Control.
2003;14:791–803.
18. Leong SL, Zainudin R, Kazan-Allen L, Robinson BW.
Asbestos in Asia. Respirology. 2015;20:548–555.
19. Tossavainen A. Global use of asbestos and the incidence
of mesothelioma. Int J Occup Environ Health.
2004;10:22–25.
20. WHO. C15plus. Cancer Incidence in Five Continents
Plus. http://ci5.iarc.fr/CI5plus/Default.aspx. Accessed
December 2020.
21. IHME, GHDx. Global Burden of Disease Study 2019 (GBD
2019) results. http://ghdx.healthdata.org/gbd-results-
tool. Accessed January 10, 2021.
22. Union Nations. Human development classification, 2018
Statistical Update. http://hdr.undp.org/sites/default/
files/2018_human_development_statistical_update.pdf.
Accessed July 30, 2020.
23. The World Bank. GDP per capita (current US$). https://
data.worldbank.org/indicator/NY.GDP.PCAP.CD. Accessed
January 31, 2022.
24. Segi M, Fujisaku S, Kurihara M. Geographical observation
on cancer mortality by selected sites on the basis of
standardised death rate. Gan. 1957;48(2):219–225.
25. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation
tests for joinpoint regression with applications to cancer
rates. Stat Med. 2000;19:335–351.
26. Leigh J, Davidson P, Hendrie L, Berry D. Malignant me-
sothelioma in Australia, 1945–2000. Am J Ind Med.
2002;41:188–201.
27. McElvenny DM, Darnton AJ, Price MJ, Hodgson JT. Me-
sothelioma mortality in Great Britain from 1968 to 2001.
Occup Med (Lond). 2005;55:79–87.
28. Burdorf A, Järvholm B, Englund A. Explaining differences in
incidence rates of pleural mesothelioma between Sweden
and the Netherlands. Int J Cancer. 2005;113:298–301.
29. Panou V, Weinreich UM, Bak J, et al. Gender differences in
asbestos exposure and disease location in 327 patients with
mesothelioma. Eur Respir J. 2017;50(suppl 61):PA4294.
30. Carbone M, Adusumilli PS, Alexander HR Jr, et al. Me-
sothelioma: scientific clues for prevention, diagnosis,
and therapy. CA Cancer J Clin. 2019;69:402–429.
31. Guo Z, Carbone M, Zhang X, et al. Improving the accu-
racy of mesothelioma diagnosis in China. J Thorac Oncol.
2017;12:714–723.
32. Lin RT, Chien LC, Jimba M, Furuya S, Takahashi K. Imple-
mentation of national policies for a total asbestos ban: a
global comparison. Lancet Planet Health. 2019;3:e341–
e348.
33. Bianchi C, Bianchi T. Malignant mesothelioma: global
incidence and relationship with asbestos. Ind Health.
2007;45:379–387.
802 Huang et al
34. Reid A, de Klerk NH, Magnani C, et al. Mesothelioma risk
after 40 years since first exposure to asbestos: a pooled
analysis. Thorax. 2014;69:843–850.
35. Rake C, Gilham C, Hatch J, Darnton A, Hodgson J, Peto J.
Occupational, domestic and environmental mesotheli-
oma risks in the British population: a case-control study.
Br J Cancer. 2009;100:1175–1183.
36. Boffetta P, Donato F, Pira E, Luu HN, La Vecchia C. Risk of
mesothelioma after cessation of asbestos exposure: a
systematic review and meta-regression. Int Arch Occup
Environ Health. 2019;92:949–957.
37. Lacourt A, Rinaldo M, Gramond C, et al. Co-exposure to
refractory ceramic fibres and asbestos and risk of pleural
mesothelioma. Eur Respir J. 2014;44:725.
38. De Bruin ML, Burgers JA, Baas P, et al. Malignant meso-
thelioma after radiation treatment for Hodgkin lym-
phoma. Blood. 2009;113:3679–3681.
39. Carbone M. Simian virus 40 and human tumors: it is
time to study mechanisms. J Cell Biochem. 1999;76:189–
193.
40. Carbone M, Albelda SM, Broaddus VC, et al. Eighth in-
ternational mesothelioma interest group. Oncogene.
2007;26:6959–6967.
41. Carbone M, Ly BH, Dodson RF, et al. Malignant meso-
thelioma: facts, myths, and hypotheses. J Cell Physiol.
2012;227:44–58.
42. Qi F, Carbone M, Yang H, Gaudino G. Simian virus 40
transformation, malignant mesothelioma and brain tu-
mors. Expert Rev Respir Med. 2011;5:683–697.
Journal of Thoracic Oncology Vol. 18 No. 6
43. Thanh TD, Tho NV, Lam NS, Dung NH, Tabata C, Nakano Y.
Simian virus 40 may be associated with developing ma-
lignant pleural mesothelioma. Oncol Lett. 2016;11:2051–
2056.
44. Zekri A-R, Mohamed W, Bahnassy A, et al. Detection of
simian virus 40 DNA sequences in Egyptian patients with
different hematological malignancies. Leuk Lymphoma.
2007;48:1828–1834.
45. Comar M, Rizzardi C, De Zotti R, et al. SV40 multiple
tissue infection and asbestos exposure in a hyperen-
demic area for malignant mesothelioma. Cancer Res.
2007;67:8456–8459.
46. Kwak K, Cho S-i, Paek D. Future incidence of malignant
mesothelioma in South Korea: updated projection to
2038. Int J Environ Res Public Health. 2021;18:6614.
47. Aoe K, Hiraki A, Fujimoto N, Gemba K, Kishimoto T. The
first nationwide survival analysis of Japanese mesothe-
lioma patients from vital statistics of Japan. J Clin
Oncol. 2010;28(suppl 15):e12007–e12007.
48. Smittenaar CR, Petersen KA, Stewart K, Moitt N. Cancer
incidence and mortality projections in the UK until 2035.
Br J Cancer. 2016;115:1147–1155.
49. Park D, Choi S, Ryu K, Park J, Paik N. Trends in occupa-
tional asbestos exposure and asbestos consumption over
recent decades in Korea. Int J Occup Environ Health.
2008;14:18–24.
50. Baumann F, Ambrosi J-P, Carbone M. Asbestos is not just
asbestos: an unrecognised health hazard. Lancet Oncol.
2013;14:576–578.