Oral Oncology 102 (2020) 104551

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Oral Oncology
journal homepage: www.elsevier.com/locate/oraloncology

Global patterns and trends in cancers of the lip, tongue and mouth T
Adalberto Miranda-Filho, Freddie Bray ⁎

Section of Cancer Surveillance, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France

ARTICLE INFO ABSTRACT

Keywords: Objectives: Global descriptions of international patterns and trends in oral cancer are informative in providing
Lip cancer insight into the shifting epidemiologic patterns and the potential prevention of these tumours. We present global
Tongue cancer statistics on these cancers using the comprehensive set of national estimates and recorded data collated at the
Mouth cancer International Agency for Research on Cancer (IARC).
Incidence
Methods: The estimated number of lip and oral cavity cases and deaths in the 185 countries for the year 2018
Mortality
was extracted from IARC’s GLOBOCAN database of national estimates. To examine trends, recorded data series
on lip and oral cavity cancers, as well as corresponding population-at-risk data were extracted from successive
volumes of Cancer Incidence in Five Continents.
Results: Globally, the highest incidence was found in South-Central Asia and parts of Oceania, with the highest
estimated incidence rates in Papua New Guinea, Pakistan and India. The highest observed rates of lip cancer
were in Australia, while India had the highest incidence rates of mouth and oral tongue cancer. Trends are
diverse, with lip cancer incidence rates continuing to decrease for both sexes; the incidence rates of mouth
cancer are also in decline in males, although increasing rates among females were observed in some populations.
Conclusion: There are some grounds for optimism given the prospects for control of these cancers. Primary
prevention should however focus on the reduction of the main causes, namely, tobacco and alcohol consump-
tion.

Introduction
Cancers of the lip and oral cavity, comprising cancers of the lip,
tongue and mouth collectively represent the 16th most common neo-
plasm worldwide, with almost 355,000 new diagnoses and over
177,000 deaths estimated in 2018 [1]. The tumours begin at the ver-
million border of the lips and extend to the buccal mucosa throughout
the tongue, mouth, floor and palate [2]; they arise primarily from
epithelium cells, and almost 90% are oral squamous cell carcinoma
(OSCC) in origin [2]. Overall survival proportions vary by geographic
region, topography and stage; in England, for example, approximately
60% of patients are expected to survive three years after diagnosis [3].
Prognosis is often poorer in transitioning countries.
Oral cancers may be preventable either by reducing exposure to risk
factors, or by screening for oral potentially malignant disorders
(OPMDs) [4]. In terms of the former intervention, a substantial shift in
the patterns and trends of oral cancer has been reported in high income
countries over the last 30 years, driven by a changing prevalence and
distribution of key risk factors [5]. Alcohol consumption is associated
with oral cancer, as is an interaction with tobacco smoking [6]. De-
creasing the morbidity and mortality from oral cavity cancers in tran-
sitioning regions with the highest burden remains a priority; in South
Asia, for example, the major risk factors remain oral tobacco con-
sumption, which includes the consumption of betel quid, with or
without tobacco [7]. There are other risk factors for specific subtypes:
high-risk Human Papillomavirus (HPV) has been linked to cancers in
the oropharyngeal regions (including base of tongue, lingual tonsil and
soft palate) in subpopulations in selected countries (men, younger ages,
of European origin, higher SES), whereas lip cancers are strongly as-
sociated with ultraviolet radiation (UVR) from sunlight exposure [8,9].
Given the complex dynamics of the underlying risk factors, global
descriptions of international patterns and trends in oral cancer are in-
formative in providing insight into the shifting epidemiologic patterns
and the potential prevention of these tumours. We thus present global
statistics on these cancers using the comprehensive set of national es-
timates, as well as the high-quality recorded data provided by popu-
lation-cased cancer registries (PBCR), as collated and compiled at the
International Agency for Research on Cancer (IARC).

⁎
Corresponding author.
E-mail address: brayf@iarc.fr (F. Bray).

https://doi.org/10.1016/j.oraloncology.2019.104551
Received 30 April 2019; Received in revised form 1 October 2019; Accepted 21 December 2019
1368-8375/ © 2019 Published by Elsevier Ltd.
A. Miranda-Filho and F. Bray
Methods
Data sources and population
The estimated number of lip and oral cavity cases and deaths for the
year 2018 was extracted from IARC’s GLOBOCAN database of national
estimates in 185 countries, available at the Global Cancer Observatory
(http://gco.iarc.fr). The GLOBOCAN methods of estimation rely upon
the best available cancer incidence and mortality data in a given
country in assembling regional and global profiles. A detailed account
of the methods is described elsewhere by Ferlay and colleagues [10].
Morphological groups of oral cancer are classified according to the
International Classification of Diseases for Oncology (ICD-O) and con-
verted to the International Classification of Disease (ICD-10) as lip
(C00), tongue [base of tongue (C01) and other and unspecified parts of
the tongue (C02)] and Mouth [gum (C03), floor of the mouth (C04),
palate (C05), and other and unspecified part of the mouth (C06)].
Recorded incidence data on lip, oral tongue and mouth cancers, as
well as corresponding population-at-risk data were extracted from
successive volumes of Cancer Incidence in Five Continents (CI5) [11], a
compendium of high quality data from PBCR worldwide. We present
recent incidence rates for cancers of the lip (ICD-10 C00), other and
unspecified parts of tongue (C02) and mouth (C03-06) separately,
predominantly from Volume XI, comprising mainly the five-year diag-
nostic period 2008–2012. We also examined time trends for the cancers
of the lip and mouth for selected registries with longstanding and high
quality data over the period 1998–2012. In presenting CI5 data at the
national level where data were subnational, we assumed the aggrega-
tion of one or more subnational PBCR was however nationally re-
presentative (see the list of registries included in supplementary material).
Statistical analyses
We calculated age-specific rates per 100,000 person-years and age-
standardized rates (ASR) using the world standard population [12] by
country and sex. The estimated national age-standardized incidence
and mortality rates for 2018 are presented using global maps. Recent
patterns in the recorded incidence rates by cancer type and sex are
presented in bar charts and the time trends presented in semi-log plots
with the trends smoothed using lowess regression [13]. The Estimated
Average Annual Percentage (EAPC) of the recent trends was estimated
on fitting Poisson log-linear models [14]. All analyses were undertaken
using R software [15].
Results
Burden and geographic variations in overall national incidence and
mortality 2018
Fig. 1A and B map the estimated incidence and mortality rates re-
spectively, by country for lip and oral cavity cancers by sex in 2018.
Table 1 illustrates the corresponding rates by world region in 2018.
Globally, incidence and mortality were consistently higher among
males than females, with the highest incidence rates in South-Central
Asia, Melanesia and Australia and New Zealand. The overall incidence
rates range from 0.5 to 21.2 in males and from 0.5 to 12.0 in females. At
the national level, incidence rates in males were highest in Papua New
Guinea (27.5 per 100,000 persons-year), Pakistan (16.3), Latvia (14.6),
followed by India (13.9) and Bangladesh (12.4), respectively. In fe-
males, the very same countries presented the highest rates, namely
Papua New Guinea (15.1), Pakistan (8.1), Bangladesh (6.5), Afghani-
stan (4.6) and India (4.3). Similarly, the highest mortality rates in males
were in Papua New Guinea (12.4), Pakistan (10.9), India (7.7), Ban-
gladesh (7.4) and Afghanistan (7.3), and in females in Pakistan (6.4),
Papua New Guinea (5.4), Bangladesh (5.0), Afghanistan (4.0) and India
(3.4). On a global scale, lip and oral cavity cancers represented 2.9% of
2
Oral Oncology 102 (2020) 104551
all cancer cases among males and 1.0% among females, with the
highest overall proportion (both sexes) observed in South Eastern Asia
(9.1%).
Geographic variations in incidence rates 2008–12 by subtype
Fig. 2 displays the recorded incidence rates for lip, oral tongue and
mouth cancers in males and females in selected countries 2008–12.
Rates among men were markedly higher for all three sites relative to
women, varying up to 10-fold between registry populations. Mouth
cancer was the most frequent cancer, with incidence rates elevated in
India/Chennai (7.1), France (4.4), Slovakia (4.2), Germany (3.9) and
Brazil/Goiania (3.6), while among females, a similar pattern emerged,
with the highest rates observed in India/Chennai (3.8), Germany (1.7),
Denmark (1.6) and Netherlands (1.5), followed by France and the U.K.
(both 1.3). Oral tongue cancer was the second most common cancer,
with the highest incidence rates in males, again observed in India/
Chennai (4.5) and Slovakia (2.9), as well as Japan (2.1). Among fe-
males, the incidence rates were lower than in males, with the highest
rates found in India/Chennai (1.6), the U.K. (1.1) and Japan (1.0). In-
cidence rates were of a lower order of magnitude for cancer of the lip,
and the geographic profile somewhat different, with the highest in-
cidence rates seen in Australia (4.3 in males, 1.2 in females).
Temporal variations in incidence rates 1998–12 by subtype
Figs. 3 and 4 display the time trends in recorded incidence rates in
selected countries for lip and mouth cancers in males and females, re-
spectively. In the majority of registry populations examined, lip cancer
incidence rates have been in steady decline, particularly among men, in
countries with populations predominantly of European origin, and
where rates have been historically high, in relative terms (>2 per
100,000). Among the most rapid declines are the rates among men in
Austria, Denmark and Poland/Kielce. Although rates in women are
subject to less stability given fewer cases, rates appear to rather stable
or slightly increasing, at least up until the most recent five years in
certain countries, including Germany, Netherlands and Norway.
The temporal patterns of mouth cancer incidence indicated two
contrasting patterns between the sexes. In males, the majority of reg-
istry populations exhibited decreasing trends, notably among U.S.
blacks, and a number of European countries, including Italy, Spain,
France and Switzerland. In females, rising rates were seen in most po-
pulations, particularly in Poland/Kielce, Denmark, Slovenia, Estonia,
Slovakia, Spain, the U.K. and Japan (Fig. 5).
Discussion
This study has sought to assess the global patterns of lip, tongue and
mouth cancers using estimates provided by GLOBOCAN 2018 and ob-
served incidence over time from longstanding and high quality cancer
registries compiled in successive CI5 volumes. A number of countries in
South and Central Asia as well as Oceania present the highest rates of
lip and oral cavity cancer worldwide, with these cancers collectively the
most common form of cancer in males in India and Pakistan, and the
second most common in Papua New Guinea. Both tobacco and alcohol
consumption are well established risk factors, however, the high pre-
valence of the chewing of betel quid is a major determinant in these
high-risk countries [16], with the risk factor classified as carcinogenic
by IARC in 2009 [17]. A study in India has reported that betel quid
chewing, with or without added tobacco, increases the risk of oral
cancer, independently of other tobacco and alcohol use [18]. The si-
milarly elevated rates of overall lip and oral cavity cancers found in
Papua New Guinea and other countries in the Pacific are likely linked to
the same causes, with betel quid chewing commonly practised in the
region [19].
Trends in mouth cancer appear to be in decline in most of the male
A. Miranda-Filho and F. Bray Oral Oncology 102 (2020) 104551

Fig. 1. Map of (A) incidence and (B) mortality age-standardized rates of lip, oral cavity cancers rates by sex, all ages, 2018. Source: GLOBOCAN 2018.

Table 1
Estimated number of lip, oral cavity cancers cases and corresponding age-standardized incidence and mortality rates (ASR), by region and sub-region in males and
females, 2018. Source: GLOBOCAN 2018.
Incidence Mortality

Male Female M:F Male Female M:F2

Cases ASR1 Cases ASR1 Patients ASR1 Patients ASR1

Africa
Eastern Africa 2686 2.5 2402 2.0 1.3 2289 2.3 1906 1.6 1.4
Middle Africa 845 1.8 681 1.2 1.5 653 1.6 487 1.0 1.6
Northern Africa 1779 1.8 1346 1.2 1.5 546 0.6 461 0.4 1.3
Western Africa 1154 1.2 1164 1.1 1.1 1002 1.1 959 1.0 1.1
Southern Africa 1012 4.4 544 1.7 2.6 682 3.1 329 1.0 3.1

Americas
Caribbean 1603 6.2 685 2.1 3.0 554 2.0 203 0.6 3.6
Central America 1192 1.4 1463 1.5 0.9 500 0.6 437 0.4 1.4
North America 18652 6.3 8460 2.4 2.6 3509 1.1 1689 0.4 2.8
South America 9959 4.3 4996 1.7 2.5 4449 1.9 1731 0.6 3.5

Asia
Eastern Asia 31074 2.4 16458 1.2 2.0 13752 1.0 7310 0.5 2.1
South-Central Asia 118716 12.9 41034 4.5 2.9 67330 7.4 31521 3.5 2.1
South-Eastern Asia 10234 3.2 6584 1.8 1.8 5327 1.7 3215 0.9 1.9
Western Asia 2411 2.1 1395 1.1 1.9 849 0.8 635 0.5 1.5

Europe
Central and Eastern Europe 16805 8.0 5901 1.8 4.4 9593 4.5 2508 0.8 5.9
Northern Europe 5579 6.2 3241 3.0 2.1 1711 1.8 914 0.7 2.6
Southern Europe 7587 5.0 4017 1.9 2.6 2549 1.6 1298 0.5 3.1
Western Europe 12210 6.9 6545 3.2 2.2 3767 2.0 1723 0.6 3.1

Oceania
Australia and New Zealand 2179 9.4 1030 3.7 2.5 320 1.2 200 0.6 2.1
Melanesia 711 21.2 489 12.0 1.8 300 9.4 162 4.2 2.2

1
Age-standardised rates per 100,000 (World).
2
Male:Female ratio of ASR.

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A. Miranda-Filho and F. Bray Oral Oncology 102 (2020) 104551

Fig. 2. Bar chart of age-standardized incidence rates of lip vs. oral tongue vs. mouth cancer in selected registry populations by sex, all ages, circa 2008–2012. Source:
Cancer Incidence in Five Continents XI. Footnote: Registries included are: Australia (Queensland, South Australia, Tasmania, Victoria, Western Australia, Northern-
Territories), Austria, Brazil/Goiania, Canada National (excl. Nunavut, Quebec and Yukon), China (Shanghai, Jiashan, Zhongshan, Harbin), Colombia/Cali, Croatia,
Denmark, Estonia, France (Bas-Rhin, Calvados, Doubs, Haut-Rhin, Manche, Herault, Isere, Somme, Loire-Atlantique, Martinique), Germany (Hamburg, Saarland),
India/Chennai, Italy (Parma, Ragusa, Romagna, Naples, Biella, Veneto, Modena, Ferrara), Japan (Miyagi, Nagasaki, Osaka, Fukui), Republic of Korea (Busan, Seoul,
Ulsan, Gwangju, Incheon), Netherlands, New Zealand, Norway, Poland/Kielce, Slovakia, Slovenia, Spain (Basque-Country, Tarragona, Granada, Murcia, Navarra,
Albacete, Girona, Canary-Islands, Cuenca), Switzerland (Geneva, Neuchatel, St Gall-Appenzell, Vaud, Valais, Ticino), Thailand (ChiangMai, KhonKaen, Songkhla,
Lampang), United Kingdom (Scotland, Northern-Ireland, England North-East, England North-West, England Yorkshire-Humber, England East-Midlands, England
West-Midlands, England East-England, England London, England South-East, England South-West), United States [USA SEER (9 registries) White and Black].

populations studied, whereas rising incidence was commonly observed
among females. The trends in rates are consistent with the global pat-
terns and trends in tobacco and alcohol consumption [20,21] and the
causal role of smoking and smokeless tobacco consumption on oral
cancers [22,23]. The impact of cigarette smoking on the historical
trends of mouth cancer is seen in the similarity of mouth cancer trends
with lung cancer two decades on; lung cancer rates continue to decrease
in males but increase in females in several European countries, coin-
ciding with time-lagged tobacco consumption [24].
A marked variation in the rates of lip cancer across registry areas
was found, with up to a four-fold variation in incidence. The elevated
incidence in Australian populations has been reported previously
[25,26], and the aetiology of lip cancer is reasonably well understood.
An elevated risk is predominantly linked to outdoor occupations, in-
cluding the fishing industry [27] and farming, as well as being resident
in rural regions [28]. The central cause is exposure to solar radiation
(UVR), with for example, Actinic Cheilits considered a potential pre-
malignant lesion caused by chronic exposure to sunlight [29]. That lip
cancer is more common in white than black populations in the U.S. is in
line with the higher frequency of the disease in lighter-skinned popu-
lations, while pigment levels of darker-skinned populations may be
protective [8]. The lower incidence among females has been partially
attributed to use of lipstick, which in theory would protect users against
sunlight exposure [30].
Our results revealed that the incidence rates of lip cancer have ei-
ther decreased or remained stable in several registry areas worldwide
over the last 15 years. The pattern in Australia, the U.S. and a number
of European countries is likely explained by a declining number of the
working population in outdoor occupations [31], possibly coupled with
increases in primary prevention of solar radiation by outdoor workers,
via sunscreen use and protective clothing and headwear [32,33]. Ex-
isting evidence also links tobacco smoking using pipes to lip and oral
cavity cancer [22], and thus the observed trends may be partially ex-
plained by a decreasing prevalence of smoking in recent decades
[20,34].
The incidence of oral tongue cancer in Chennai/India is three-fold
higher compared to the U.S. In parts of India, oral tongue represents a
higher proportion of tongue cancer, while the base of the tongue more
common site in the U.S., (Supplementary Table). The causes for the
global variations in the incidence of oral tongue cancer are likely
multifactorial. The tongue overlaps with the palate, extending to the
border of oropharynx, while the anterior two-thirds are located in the
oral cavity and the posterior third is in the pharynx [35]. The anato-
mical distinction are important as the biology and natural history of
these tumours are significantly different [36,37]. Cancers of the oral
tongue have been traditionally associated with tobacco and alcohol
consumption [38] with the highest incidence rates found in India.
Sankaranaryanan and colleagues [39] reported a positive association
between the consumption of tobacco smoking and alcohol, with the
higher risk of cancer in the oral tongue, floor and mouth in a case-
control study in Kerala. Tobacco chewing was also associated with oral
cancer in both sexes, independent of the use of tobacco [40]. In addi-
tion, marijuana consumption is suspected to increase the risk of oral
cancers, particularly in the oropharynx, although its association with
oral tongue remains unclear [41]. There is strong evidence to suggest
that Human Papillomavirus (HPV) increases the risk of cancers in the
oropharyngeal region (including base of tongue, lingual tonsil and soft
palate) [42,43]. Chaturvedi and colleagues reported an increasing in-
cidence of HPV-related cancer (which includes certain sites of the
tongue) in white men but not white women in the U.S., possibly im-
plicating changes in sexual behaviour as a critical driver [44].
Despite the continued high burden of lip and oral cavity cancers in
several regions and specific countries, there is still reasons for opti-
mism. Many of these cancers are preventable. Oral visual screening
requires knowledge of the anatomy and natural history of oral cancer
and the clinical and pathological features of the OPMDs and preclinical
cancers [4,31], therefore screening programs with health workers
trained in detection of OPMDs in high risk groups have been described
as efficient in decreasing mortality, as was seen in a rural region in
India [16]. However, the cost-effectiveness of oral screening programs
in developing countries is still the subject of debate, in part due to the
limited availability of health care resources [45]. Tobacco smoking and
chewing and alcohol consumption are associated with leucoplakias,
which are among the most prevalent OPMDs; interventions that seek to
eliminate or reduce tobacco and alcohol consumption must be im-
plemented where cost-effective. Tobacco cessation, alcohol control

4
A. Miranda-Filho and F. Bray Oral Oncology 102 (2020) 104551

Fig. 3. Time trends in age-standardized incidence rates of lip vs. mouth cancer in selected registry populations, males, all ages 1998–2012. Source: Cancer Incidence
in Five Continents plus.

5
A. Miranda-Filho and F. Bray Oral Oncology 102 (2020) 104551

Fig. 4. Time trends in age-standardized incidence rates of lip vs. mouth cancer in selected registry populations, females, all ages 1998–2012. Source: Cancer
Incidence in Five Continents plus.

6
A. Miranda-Filho and F. Bray
Fig. 5. Estimated Annual Percentage Change (EAPC) of the trends in age-standardized rates of lip vs. mouth cancer in selected registry populations by sex,
1998–2012; sorted in descending order according to EAPC in men by subtype. Source: Cancer Incidence in Five Continents plus.
interventions are all cost-effective, even for LMICs [4].
The interpretation of the global estimates of lip and oral cavity
cancer should be undertaken with some caution. An important limita-
tion is the definition of oral cancer in GLOBOCAN 2018, which includes
the base of tongue (ICD-10 C01) combined with other and unspecified
parts of tongue (C02). The proportion of cancers in the base of the
tongue (C01) and oral tongue (C02) varies considerably among popu-
lations and by sex; for example in Japan the former represents only 12%
of the two subsites combined in males and 5% in females, while in the
U.S. (black population) these cancers represent circa 64% in males and
54% in females (Supplementary Table).
In addition, the robustness of national estimates in GLOBOCAN
varies by country, depending on the availability of high quality in-
cidence and mortality data. The recorded incidence data from national
or subnational registries included in CI5 are however considered of high
quality, in terms of comparability, accuracy and completeness. Our
study provides the most complete global and national estimates for all
world areas produced in the GLOBOCAN database and presented at
IARC’s Global Cancer Observatory (http://gco.iarc.fr). These resources
disseminate standardised information derived largely from the data
provided by PBCR worldwide, the critical institutions providing local
cancer statistics to inform national cancer control policies.
In summary, this study provides a snapshot of the global patterns
and trends in lip, tongue and mouth cancer worldwide. The highest
incidence rates remain in South and Central Asia and selected countries
and territories of the Pacific. Lip cancer incidence rates has a pre-
dominantly UV-related aetiology, with uniformly declining rates partly
the result of occupational changes, mainly among peoples of European
origin in high-income countries. Trends in the incidence rates of mouth
cancer are also in decline in males, although the increasing rates among
females in some populations warrants attention. There are some
grounds for optimism given the prospects for control of these cancers.
Preventative measures and screening programs to treat premalignant
lesions should be prioritized in high-risk populations, while primary
7
Oral Oncology 102 (2020) 104551
prevention should focus on the reduction of the main causes: tobacco
smoking and alcohol consumption.
Disclaimer
Where authors are identified as personnel of the International
Agency for Research on Cancer / World Health Organization, the au-
thors alone are responsible for the views expressed in this article and
they do not necessarily represent the decisions, policy or views of the
International Agency for Research on Cancer / World Health
Organization.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
Acknowledgements
We would like to thank the Directors and staff of the population-
based cancer registries worldwide who compiled and submitted their
data for IARC’s Cancer Incidence in Five Continents and GLOBOCAN
projects used in this paper.
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.oraloncology.2019.104551.
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