Articles

Estimates of incidence and mortality of cervical cancer in

2018: a worldwide analysis
Marc Arbyn, Elisabete Weiderpass, Laia Bruni, Silvia de Sanjosé, Mona Saraiya, Jacques Ferlay, Freddie Bray

Summary
Background The knowledge that persistent human papillomavirus (HPV) infection is the main cause of cervical Lancet Glob Health 2020;
cancer has resulted in the development of prophylactic vaccines to prevent HPV infection and HPV assays that 8: e191–203

detect nucleic acids of the virus. WHO has launched a Global Initiative to scale up preventive, screening, and Published Online
December 4, 2019
treatment interventions to eliminate cervical cancer as a public health problem during the 21st century. Therefore,
https://doi.org/10.1016/
our study aimed to assess the existing burden of cervical cancer as a baseline from which to assess the effect of this S2214-109X(19)30482-6
initiative. This online publication has
been corrected. The corrected
Methods For this worldwide analysis, we used data of cancer estimates from 185 countries from the Global Cancer version first appeared at
thelancet.com/lancetgh on
Observatory 2018 database. We used a hierarchy of methods dependent on the availability and quality of the source
Dec 14, 2021
information from population-based cancer registries to estimate incidence of cervical cancer. For estimation of
See Comment page e155
cervical cancer mortality, we used the WHO mortality database. Countries were grouped in 21 subcontinents and
Unit of Cancer Epidemiology,
were also categorised as high-resource or lower-resource countries, on the basis of their Human Development Index. Belgian Cancer Centre,
We calculated the number of cervical cancer cases and deaths in a given country, directly age-standardised incidence Sciensano, Brussels, Belgium
and mortality rate of cervical cancer, indirectly standardised incidence ratio and mortality ratio, cumulative incidence (M Arbyn PhD); International
and mortality rate, and average age at diagnosis. Agency for Research on Cancer,
Lyon, France (E Weiderpass PhD,
J Ferlay Ir, F Bray PhD);
Findings Approximately 570 000 cases of cervical cancer and 311 000 deaths from the disease occurred in 2018. Cervical Consortium for Biomedical
cancer was the fourth most common cancer in women, ranking after breast cancer (2·1 million cases), colorectal Research in Epidemiology and
cancer (0·8 million) and lung cancer (0·7 million). The estimated age-standardised incidence of cervical cancer was Public Health, Barcelona, Spain
(L Bruni MD); Unit of Infections
13·1 per 100 000 women globally and varied widely among countries, with rates ranging from less than 2 to 75 per and Cancer, Catalonian
100 000 women. Cervical cancer was the leading cause of cancer-related death in women in eastern, western, middle, Institute of Oncology,
and southern Africa. The highest incidence was estimated in Eswatini, with approximately 6·5% of women developing Barcelona, Spain (L Bruni);
cervical cancer before age 75 years. China and India together contributed more than a third of the global cervical PATH, Seattle, WA, USA
(S Sanjosé PhD); and Centers for
burden, with 106 000 cases in China and 97 000 cases in India, and 48 000 deaths in China and 60 000 deaths in India. Disease Control and
Globally, the average age at diagnosis of cervical cancer was 53 years, ranging from 44 years (Vanuatu) to 68 years Prevention, Division of Cancer
(Singapore). The global average age at death from cervical cancer was 59 years, ranging from 45 years (Vanuatu) to Prevention and Control,
Atlanta, GA, USA
76 years (Martinique). Cervical cancer ranked in the top three cancers affecting women younger than 45 years in
(M Saraiya MD)
146 (79%) of 185 countries assessed.
Correspondence to:
Dr Marc Arbyn, Unit of Cancer
Interpretation Cervical cancer continues to be a major public health problem affecting middle-aged women, Epidemiology, Belgian Cancer
particularly in less-resourced countries. The global scale-up of HPV vaccination and HPV-based screening—including Centre, B1050 Brussels, Belgium
self-sampling—has potential to make cervical cancer a rare disease in the decades to come. Our study could help [email protected]

shape and monitor the initiative to eliminate cervical cancer as a major public health problem.

Funding Belgian Foundation Against Cancer, DG Research and Innovation of the European Commission, and The
Bill & Melinda Gates Foundation.

Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Introduction Consistent evidence indicates that the licensed

10 years ago, cervical cancer ranked as the third bivalent and quadrivalent HPV vaccines containing
most common cancer among women worldwide. HPV16 and HPV18 antigens protect with high efficacy
However, in 42 low-resource countries, it was the most against infection and precancerous cervical lesions
common cancer in women.1 The knowledge that persistent associated with these types when individuals are not yet
infection with carcinogenic human papillomavirus (HPV) exposed.3 Both types jointly cause 70–75% of all cervical
types is the main cause in triggering the develop­ment of cancers and 40–60% of its precursors.4,5 In the past few
cervical cancer has opened new pathways for primary years, a nonavalent vaccine has also been licenced,
and secondary prevention.2 The implementation of which protects against seven carcinogenic HPV types
both methods of prevention can make cervical cancer that, together, cause approximately 90% of cervical
occurrence and death largely avoidable. cancers.6

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Research in context
Evidence before this study baseline to measure the future achievements regarding the
The Global Cancer Observatory (GLOBOCAN) is a ambitious rollout of the WHO Global Initiative to eliminate
regularly-updated database, compiled by the International cervical cancer as a public health problem in every country of
Agency for Research on Cancer, of global estimates of the world.
incidence and mortality rate for 36 cancers and for all cancers
Implications of all the available evidence
combined. For compiling the estimates, recorded data of high
Today, new tools of primary prevention (prophylactic HPV
quality from national or subnational cancer registry sources
vaccination) and secondary prevention (screening with
are used where possible, otherwise the best available local
validated HPV assays and treatment of cervical precancerous
sources are used in their absence. Previous GLOBOCAN
lesions) have been shown to be effective. The ambition of
estimates for 2008 indicated that approximately
WHO is to reduce the ASIR of cervical cancer to less than 4 per
530 000 cervical cancer cases and 275 000 deaths had occurred
100 000 women worldwide by vaccinating 90% of all girls by
worldwide, with 85% of cases occurring in less developed
age 15 years, screening 70% of women twice in the age range
countries. The estimated annual age-standardised incidence
of 35–45 years, and treating at least 90% of all precancerous
rate (ASIR) was 15 per 100 000 women globally and ranged
lesions detected during screening. Modellers have estimated
from less than 1 to 56 per 100 000. Cervical cancer was the
that this goal might be reached within a few decades in
leading cause of cancer-related death among women in sub-
high-resource countries, but might take until the end of the
Saharan Africa, central America, south-central Asia, and
21st century for the goal to be reached in the lowest-resource
Melanesia.
countries. Nevertheless, the return of investment will be
Added value of this study highest in low-resource countries; for example, using the
Our study provides updated estimates of the cervical cancer cumulative incidence estimates from GLOBOCAN and
burden 10 years after the 2008 GLOBOCAN publication. In assuming 70% HPV vaccination effectiveness, we can calculate
2018, cervical cancer remained a major public health problem, that only 20 girls would need to be vaccinated in eSwatini (the
ranking as the fourth most common cause of cancer incidence country with the highest estimated incidence) to avoid one
and mortality in women worldwide. Cervical cancer was the case of cervical cancer, whereas the equivalent number needed
main cause of cancer-related deaths in women in eastern, would be 238 girls in the USA. Ensuring the availability of
middle, southern, and western Africa. We observed a recorded data of good quality from population-based cancer
significant positive correlation between national ASIRs and registries will be essential for monitoring local progress
corresponding estimates of human papillomavirus (HPV) towards the cervical cancer elimination goal.
prevalence. The 2018 estimates presented here provide a

The treatment of precancerous lesions detected by nations of the world to mobilise resources to make an
microscopic inspection of cells scraped from the cervix end to suffering from cervical cancer.13
has been the paradigm of secondary prevention of Now more than ever, effective cervical cancer control
cervical cancer for half a century.7 Although cytological planning requires access to accurate statistics. According
screening has undoubtedly led to a major decline in to WHO, one of the fundamental steps in the action plan
cervical cancer burden in several resource-rich countries, for non-communicable diseases is to establish a high-
the method might have reached its limits, with reports quality surveillance and monitoring system that
from several countries with longstanding high-quality provides, as a minimum standard, reliable population-
Pap smear-based programmes indicating that trends based statistics data on the major non-communicable
have either stabilised or began to rise.8 Meta-analyses diseases.14
and pooled analyses of randomised trials have shown Using the 2018 estimates of the worldwide cancer
that screening with HPV tests protects better against burden compiled by the International Agency for
future cervical precancerous lesions and invasive cancers Research on Cancer (IARC) on the basis of available
than screening by cytology9,10 and, therefore, virological cancer registry and vital statistics data, we describe in
screening programmes are becoming increasingly this study the existing patterns of cervical cancer
recommended.11,12 incidence and mortality rate alongside HPV prevalence
Given the availability of these new preventive tools, data, thus allowing a comprehensive baseline assessment
public health experts are challenged to define of the global cervical cancer burden.15
comprehensive integrated strategies that combine HPV
vaccination and cervical cancer screening that fit the Methods
target populations within the limits of cost-effectiveness. Study design and data sources
In 2018, in a greatly changing preventive landscape, the We extracted the estimated number of cases of and deaths
WHO Director-General launched an ambitious call to all from cancer of the cervix uteri (International Classification

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 Total female Number ASIR (per SIR CIR* Proportion Rank Rank Number ASMR (per SMR CMR* Proportion Rank Rank
population of cases 100 000 of all (all ages) (15–44 years) of deaths 100 000 of all (all ages) (15–44 years)
(millions) women) cancers women) cancers
World 3782·1 569 847 13·1 100 1·4% 6·9% 4 2 311 365 6·9 100 0·8% 7·5% 4 2
HDI level
Very high 680·2 90 032 9·6 67 0·9% 2·8% 12 3 36 305 3·0 44 0·3% 2·6% 12 2
High 1211·9 180 597 11·1 85 1·1% 6·1% 6 3 85 296 4·9 73 0·5% 5·4% 7 2
Medium 1339·8 204 130 15·7 118 1·7% 14·4% 2 2 122 097 9·6 139 1·1% 14·3% 2 2
Low 536·7 93 285 26·7 194 3·0% 17·7% 2 2 66 643 20·0 283 2·4% 22·4% 1 2
Subcontinents
Eastern Africa 218·4 52 633 40·1 289 4·4% 26·5% 1 1 37 017 30·0 425 3·5% 27·5% 1 1
Middle Africa 84·6 12 635 26·8 188 3·1% 23·6% 2 2 9418 21·1 292 2·5% 25·1% 1 2

www.thelancet.com/lancetgh Vol 8 February 2020

Northern Africa 118·3 7652 7·2 52 0·8% 5·2% 4 5 5243 5·1 71 0·6% 6·5% 3 7
Southern Africa 33·6 14 409 43·1 338 4·3% 23·4% 2 1 6480 20·0 297 2·1% 20·7% 1 1
Western Africa 189·7 31 955 29·6 199 3·5% 23·3% 2 2 23 529 23·0 309 2·8% 26·6% 1 2
Caribbean 22·3 4200 15·5 121 1·6% 8·1% 4 2 2464 8·5 127 0·9% 8·7% 4 2
Central America 90·5 12 406 13·0 101 1·3% 9·1% 2 3 6619 7·0 104 0·8% 10·9% 2 2
South America 217 39 581 15·2 118 1·6% 7·7% 3 2 19 235 7·1 106 0·8% 8·2% 4 2
Northern America 183·7 15 502 6·4 45 0·6% 1·7% 14 3 5852 1·9 28 0·2% 1·8% 12 3
Eastern Asia 807·4 126 874 10·9 81 1·1% 5·1% 6 3 54 547 4·1 62 0·5% 4·1% 8 2
Southeastern Asia 328·3 62 456 17·2 131 1·9% 12·4% 2 2 35 738 10·0 144 1·2% 12·6% 2 2
South-central Asia 954·1 120 924 13·0 97 1·4% 13·9% 2 2 75 133 8·2 119 0·9% 13·8% 2 2
Western Asia 129·3 5092 4·1 31 0·4% 2·7% 12 5 2993 2·5 36 0·3% 3·3% 10 7
Central-eastern Europe 154·6 35 940 16·0 114 1·6% 5·9% 5 2 16 011 6·1 83 0·7% 5·2% 8 1
Northern Europe 53·1 6319 9·5 61 0·9% 2·1% 13 3 2060 2·1 32 0·2% 1·6% 17 2
Southern Europe 78·3 9155 7·8 54 0·8% 2·3% 13 3 3512 2·2 33 0·2% 2·0% 15 2
Western Europe 98·4 9658 6·8 48 0·7% 1·7% 15 4 4246 2·1 33 0·2% 1·8% 16 3
Australia and New Zealand 14·8 1114 6·0 41 0·6% 1·5% 14 5 403 1·7 25 0·2% 1·6% 18 3
Melanesia 5·2 1254 27·7 219 2·6% 15·4% 2 2 825 19·0 290 1·9% 17·5% 2 1
Micronesia 0·3 51 18·6 141 2·1% 11·2% 3 2 22 7·8 114 1·0% 8·4% 3 4
Polynesia 0·3 37 10·7 81 1·2% 5·0% 6 3 18 5·2 73 0·6% 4·9% 5 2

HDI=Human Development Index. ASIR=world age-standardised incidence rate. SIR=standardised incidence ratio. CIR=cumulative incidence rate of developing cervical cancer. ASMR=world age-standardised mortality rate. SMR=standardised mortality
ratio. CMR=cumulative mortality rate of cervical cancer. *Before age 75 years.

Table: Burden of cervical cancer incidence and mortality in 2018 worldwide and by the four-tier HDI and by sub-continent
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Age-standardised incidence
(per 100 000 women-years)
0 to <3 (7 countries) 21 to <24 (15 countries)
3 to <6 (18 countries) 24 to <27 (8 countries)
6 to <9 (27 countries) 27 to <30 (6 countries)
9 to <12 (23 countries) 30 to <35 (9 countries)
12 to <15 (20 countries) 35 to <40 (4 countries)
15 to <18 (16 countries) 40 to 80 (15 countries)
18 to <21 (17 countries)

Figure 1: Geographical distribution of world age-standardised incidence of cervical cancer by country, estimated for 2018

Age-standardised mortality (per 100 000 women-years)

0 to <1·5 (8 countries) 12·0 to <15·0 (14 countries)
1·5 to <3·0 (34 countries) 15·0 to <18·0 (9 countries)
3·0 to <4·5 (21 countries) 18·0 to <21·0 (8 countries)
4·5 to <6·0 (18 countries) 21·0 to <24·0 (7 countries)
6·0 to <7·5 (14 countries) 24·0 to <27·0 (4 countries)
7·5 to <9·0 (12 countries) 27·0 to <30·0 (2 countries)
9·0 to <12·0 (19 countries) 30·0 to 42·0 (15 countries)

Figure 2: Geographical distribution of world age-standardised mortality rate of cervical cancer by country, estimated for 2018

of Diseases tenth edition [ICD-10] code C53) in Strengthening the Reporting of Observational Studies in
185 countries in 2018 from the Global Cancer Observatory Epidemiology statement, containing the checklist of
(GLOBOCAN) 2018 database, as published by the items to be included in reports of observational studies, is
See Online for appendix IARC.16,17 Data were aggregated by 5-year age groups, provided in the appendix (pp 15–20).
except for the oldest age group comprising women aged Data sources and methods of estimation for incidence
85 years or older. In this study, the 5-year age groups from and mortality rate have been described in detail
15 years to 44 years were merged to assess the burden of elsewhere.17 Briefly, for estimation of incidence, we
For the WHO mortality
cervical cancer in younger women, particularly because applied a hierarchy of methods that were dependent on
database see http://www.who. few deaths in this age range are classified as uterine the availability and quality of the source information from
int/whosis/mort/download/en/ cancer not otherwise specified (ICD-10 code C55).18,19 A population-based cancer registries; methods ranged from

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a short-term extrapolation of high-quality recorded A Africa

national incidences through short-term prediction Mortality Incidence
models20 to the use of observed rates from one or more
Malawi
neighbouring countries in the same region in the
eSwatini
complete absence of recorded information. Burundi
For the estimation of mortality rates, we used the WHO Zimbabwe
mortality database as a source for the number of deaths Zambia
caused by cancer where available, with the figures Tanzania
adjusted for incomplete registration and corrected for ill- Uganda
defined causes of death. Studying cervical cancer Comoros
mortality is particularly difficult because the certified Guinea
cause of death often does not indicate the anatomical Burkina Faso
origin (cervix [CVX] or corpus uteri [CRP]) with sufficient Lesotho
Madagascar
precision, but rather the death is classified as death from
Mali
uterine cancer, not otherwise specified (NOS). In
Mozambique
GLOBOCAN 2018, when the proportion of NOS deaths
Liberia
was less than 25% of all uterine cancer deaths, the Senegal
corrected incidence of cervical cancer deaths (corCVXi) Guinea-Bissau
was computed by use of the following reallocation rule:18 Angola
Mauritania
corCVXi = CVXi + NOSi*CVXi/(CVXi + CRPi) Côte d’Ivoire
Rwanda
For some countries with reliable national cancer The Gambia
registries and survival statistics, we estimated corCVXi Ghana
from age-specific incidence and the 5-year relative survival South Sudan

probability.17 No data were available to allow adjustment Kenya

Somalia
for hysterectomy.
Cameroon
DR Congo
Stratification by geographical region and human
Benin
development Nigeria
Countries were grouped in 21 subcontinents as defined by South Africa
the UN except for Cyprus, which was reallocated to Togo
southern Europe.18 In this study, Micronesia and Polynesia Central African Republic
were aggregated to comprise one sub­continental region. Botswana
Countries were categorised by the Human Development Chad
Index (HDI), a composite index of life expectancy, Equatorial Guinea
education, and per-capita income indicators developed by Ethiopia
the UN Development Programme21 (appendix p 1) that Namibia

ranks countries into four tiers of human development Gabon

Morocco
(low, medium, high, and very high). By use of the HDI
São Tomé and Príncipe
estimates for 2016, countries within the highest of the
Congo (Brazzaville)
four tiers are interchangeably denoted as the highest-
Sierra Leone
resource countries and countries in the remaining three Eritrea
tiers are denoted as lower-resource countries. Cape Verde
Djibouti
Statistical analysis Niger
We calculated the number of cervical cancer cases and Sudan
deaths in a given country by applying the estimated age- Algeria
specific and sex-specific rates for 2018 to the corres­ Mauritius
ponding population strata. We calculated the directly Libya
age-stan­dar­
dised incidence rate (ASIR) and age- France, La Reunion
Tunisia
standardised mortality rate (ASMR) using the world
Egypt
standard population.22 We derived the indirectly
standardised incidence ratio (SIR) and mortality ratio 0 10 20 30 40 50 60 70 80
Cases or deaths per 100 000 women-years
(SMR) from the ratio of
(Figure 3 continues on next page)
ΣOi/ΣEi

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B The Americas
The geographical distribution of the age-standardised
Mortality Incidence
incidence and mortality rate per 100 000 women by
country is displayed in choropleth world maps, using
Jamaica
categories of ascending rate groupings as used in earlier
Bolivia
Guyana
publications1,24 to allow comparisons.
Belize
Paraguay Role of the funding source
Suriname The funders of the study had no role in study design,
Nicaragua data collection, data analysis, data interpretation, or
Honduras writing of the report. The corresponding author had full
Haiti access to all the data in the study and had final
Guatemala responsibility for the decision to submit for publication.
Venezuela
Peru Results
Saint Lucia
In 2018, approximately 570 000 women developed
Dominican Republic
cervical cancer and 311 000 women died from it,
Trinidad and Tobago
corresponding to an all-ages ASIR of 13·1 per
El Salvador
Barbados
100 000 women-years and ASMR of 6·9 per 100 000
Ecuador
(table). Worldwide, cervical cancer was the fourth most
Panama common cancer among women, after breast cancer
The Bahamas (2·09 million cases), colorectal cancer (0·79 million),
Argentina and lung cancer (0·73 million); and it was also the fourth
Uruguay leading cause of cancer death among women, after
Cuba breast (627 000 deaths), lung (576 000) and
Brazil colorectal (387 000) cancers. Approximately 84% of all
Mexico cervical cancers and 88% of all deaths caused by cervical
Colombia cancer occurred in lower-resource countries (ie, those
Costa Rica
with HDI <0·80), of which 1·8% of women were
Chile
diagnosed with and 1·3% died from the disease before
French Guyana
age 75 years, in the absence of competing causes of
Puerto Rico
France, Guadeloupe
death. By contrast, in the highest-resource countries, the
USA cumulative rates of cervical cancer incidence and
France, Martinique mortality were two to four times lower than those in
Canada lower-resource countries. The ASIR and ASMR
0 10 20 30 40 50 60 70 80 increased with decreasing level of HDI, from
Cases or deaths per 100 000 women-years an ASIR of 9·6 per 100 000 women and ASMR of 3·0 per
100 000 in countries in the very high HDI tier to an
(Figure 3 continues on next page)
ASIR of 26·7 per 100 000 and ASMR of 20·0 per 100 000
in countries in the low HDI tier (appendix p 2).
where Oi corresponds to the estimated number of cases The variations in rates are more striking when the
or deaths and Ei corresponds to their expected number, focus is on subcontinents (figures 1, 2). Overall, the
being the product of lowest incidence burden was observed in western Asia
and the lowest mortality burden was observed in
awi*Nci Australia–New Zealand (table). Rather modest incidences
(ASIR <10 per 100 000) were also noted in Australia–
(world age-specific rates multiplied by the number of New Zealand, northern America, western Europe,
women in the corresponding age stratum [i] of each northern Africa, southern Europe, and northern
country [c]). We computed the cumulative rates by Europe. The highest burden was observed in southern
summing the products of the age-specific rates (ai) Africa and eastern Africa. A very high burden of the
multiplied by the width of the corresponding age groups disease (ASIR ≥15 per 100 000) was also observed in
(ΔTi) up to age 74 years.23 western Africa, Melanesia, middle Africa, Micronesia,
southeastern Asia, eastern Europe, the Caribbean, and
CR = Σai*ΔTi South America (table).
The highest incidences (ASIR >40 per 100 000) were all
We computed the average age at diagnosis as the weighted found in countries from eastern, southern, or western
mean age using the mid-age of each 5-year age group and Africa (eSwatini , Malawi, Zambia, Zimbabwe, Tanzania,
90 years for women aged 85 years or older. Burundi, Uganda, Lesotho, Madagascar, Comoros,

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Guinea, Burkina Faso, Mali, South Africa, and

C Asia
Mozambique; figure 3). China was the country with the Mortality Incidence
highest number of cases (106 000), whereas India was the
Nepal
country with the highest estimated number of cervical
Indonesia
cancer deaths (60 000; cervical cancer incidence and
Maldives
mortality statistics at country level are detailed in the Myanmar
appendix [pp 7–14]). China and India together contributed Kyrgyzstan
35% to the global burden of cervical cancer cases and Mongolia
deaths. Bhutan
The lowest ASIR values (<5 per 100 000 women) were Cambodia
estimated in 12 countries in western Asia or the western India
part of central-south Asia (Iraq, Yemen, Iran, Palestine, Thailand
Saudi Arabia, Jordan, Kuwait, Syria, Bahrain, Qatar, Philippines
Israel, and Turkey), two countries in north Africa (Egypt Turkmenistan

and Tunisia), one country in southern Europe (Malta), Kazakhstan

Bangladesh
and one country in northern Europe (Finland). ASMR
Laos
was significantly correlated with ASIR (p<0·0001)
Timor-Leste
resulting in a very similar geographical distribution
Brunei
between the two (figures 1, 2). However, the range of Malaysia
variation was greater for SMR (ranging from 16 to 804) Armenia
than for SIR (ranging from 13 to 570). The higher rates Georgia
SMR values are in line with the observation that countries Uzbekistan
with higher ASIR had lower survival (approximated by Afghanistan
the compliment of the ratio of mortality over incidence; Pakistan
p<0·0001).25 Azerbaijan
Figure 4 displays the ranking of cervical cancer in United Arab Emirates
each country among all cancer sites in women in terms China

of number of cases, for all ages, and for women Sri Lanka
Vietnam
aged 15–44 years. In 98 (52%) of 185 countries assessed,
Oman
cervical cancer was among the three most frequent
Singapore
cancers in women of all ages (figure 4). However,
Lebanon
in women younger than 45 years, cervix cancers ranked North Korea
in the top three cancers in 146 countries (79%) Tajikistan
worldwide. Qatar
The age-specific incidence rate of cervix cancer starts Japan
rising after the age of 25 years (figure 5). In the highest- Bahrain
resource countries, a maximum of incidence is reached Syria
around the age of 40 years, whereas in lower-resource Turkey
countries, rates continued to rise markedly up to ages Kuwait
55–69 years. Globally, the average age at diagnosis of Israel

cervical cancer was 53 years, ranging from 44 years South Korea

Palestine
(Vanuatu) to 68 years (Singapore). The global average
Jordan
age at death from cervical cancer was 59 years, ranging
Saudi Arabia
from 45 years (Vanuatu) to 76 years (Martinique). The
Yemen
incidence peaked at ages 50–54 years at the global Iraq
level. The country with the earliest peak was the UK Iran
(30–34 years), whereas a large group of countries had 0 10 20 30 40 50 60 70 80
their maximal incidence in the age group of 85 years Cases or deaths per 100 000 women-years
and older (data not shown).
(Figure 3 continues on next page)

Discussion
With almost 0·6 million cases and 0·3 million deaths per variations in source information, the absolute number of
year, cervical cancer continues to constitute a major cases of cervix uteri cancer worldwide estimated in
public health problem, ranking as the fourth most GLOBOCAN increased over time (471 000 in 2000,
common cause of cancer incidence and mortality in 529 000 in 2008, and 570 000 in 2018).1,26 This rise could
women worldwide. Notwithstanding the caveats of be driven by the growth and aging of the global
interpreting estimates from different years given the population,24 and cervical cancer incidences have tended

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to decrease (ASIR 16·2 per 100 000 women in 2002,28

D Europe
15·2 in 2008,1 and 13·1 in 2018). In the previous estimates
Mortality Incidence
for 2008, cervical cancer still ranked as the third most
Romania
frequent malignant tumour, accounting for 8·7% of all
Moldova
cancers in women (excluding non-melanoma skin
Bulgaria
cancers), but dropped to fourth ranking in 2018, with
Lithuania
Serbia
6·9% of the total cancer burden. Declining incidences
Ukraine
were observed in most world regions in the first decade
Latvia of the 21st century, but exceptions were also seen in
Russia eastern Europe and sub-Saharan Africa.29 The proportion
Slovakia of cervical cancer deaths among all cancer deaths
Hungary decreased from 8·2% in 2008, to 7·5% in 2018, although
Poland the fourth place ranking of cervical cancer deaths was
Bosnia Herzegovina retained.
Estonia Because the mean age at diagnosis of cervical cancer is
Montenegro quite low compared with that of most other major cancer
Czech Republic
types, it generates proportionally greater loss of life-
Belarus
years.30 Age-specific analyses (figure 5) clearly indicated
Croatia
that cervical cancer occurred across a range of ages
North Macedonia
Ireland
during which adult women have many economic and
Slovenia
caregiving responsibilities for their families. The absence
Portugal of a further rise in incidence after age 40 years in high-
Albania resource countries could reflect cancers prevented by
France screening, although hysterectomy might have also partly
Germany contributed to a reduced number of cervical cancer cases.
Greece Considerable rate variations were noted, with incidences
Sweden ranging from less than 3 to more than 70 per
Luxembourg 100 000 women. Mortality from cervical cancer is the
Denmark malignancy with the largest inter-country range of variation
Belgium
among all cancers.27 Cervical cancer remains the leading
UK
cause of cancer death in women in 42 lower-resource
Austria
countries (appendix p 3), by contrast with being the 19th
Spain
Norway
most common cause in Finland (a high-resource country).
Italy Such remarkable geographical contrasts reflect differences
Cyprus in exposure to risk factors and serious inequalities in
Malta access to adequate screening and effective cancer treatment
Netherlands facilities.31,32 Sexually transmitted infection with high-risk
Iceland HPV types is the main aetiological factor for cervical
Switzerland cancer.33,34 We plotted the prevalence of high-risk HPV by
Finland subcontinent derived from a meta-analysis updated in
2018, involving 2·4 million women with normal cervical
E Oceania cytology against the respective standardised cervical
Papua New Guinea incidence.1,35 The scatter plot (appendix p 4) showed a clear
Fiji positive correlation (r=0·70).
Solomon Islands Other cofactors, such as some sexually transmittable
Vanuatu infections (HIV and Chlamydia trachomatis), smoking,
New Caledonia and oral hormonal contraception, might also contribute
Guam to changes and contrasts in the global cervical cancer
Samoa
burden.36–38 However, other putative factors related to
French Polynesia
socioeconomic develop­ment and transitions to a lifestyle
New Zealand
more typical of high-income countries (including
Australia
reproductive and sexual factors) seem to underpin major
0 10 20 30 40 50 60 70 80
changes in cancer risk, the effect of which was seen in
Cases or deaths per 100 000 women-years
the lowering of cervical cancer rates over time and
Figure 3: World age-standardised incidence and mortality rate for cervical cancer, estimates for 2018, ordered concomitant rises in breast cancer rates in several
by country and ranked in descending order of mortality countries with emerging economies.39,40 These societal
changes are clearly illustrated by the cervical cancer

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Incidence ranking (all ages)

1 (28 countries)
2 (58 countries)
3 (12 countries)
4–5 (30 countries)
≥6 (57 countries)

Incidence ranking (15–44 years)

1 (32 countries)
2 (82 countries)
3 (32 countries)
4–5 (25 countries)
≥6 (14 countries)

Figure 4: Ranking of cervical cancer incidence burden in 2018 relative to all other cancer sites in women of all ages (A) and aged 15–44 years (B)

incidence trends in India, which have declined in urban The low rates of cervical cancer in north America,
areas but have stayed stable in rural areas.41 A notable and northern and western Europe, and Australia and
novel public health concern is the observation of an New Zealand are probably the result of successful
upward trend in cervical cancer incidence in several cytological screening.18,48–51 These screening programmes
countries with established preventive programmes, have counteracted increased exposure to risk factors
which might be explained by increased exposure to HPV among generations born after 1945, as established from
insufficiently compensated by cytological screening.42–44 age-period-cohort analyses50,52,53 and from HPV prevalence
Parts of western Asia and northern Africa with surveys in archived biospecimens.54 However, where
incidence of cervical cancer have a low prevalence of HPV screening, management of patients with positive screen
(figure 1), most plausibly explained by societal factors results, or both were of poor quality, the cohort effect was
related to sexual behaviour.45 These countries also exhibit not balanced in the same way, resulting in trends that
low rates of other sexually related infections, such as were slightly declining, stable, or even increasing, as
HIV.46 By contrast, in areas in sub-Saharan Africa, observed in Ireland, Portugal, and in several Baltic and
Latin America, and south Asia, the high cervical cancer eastern European countries, where the burden of cervical
rates probably reflect an elevated background risk, cancer is among the highest on the European
explained by high rates of HPV and HIV transmission.47 continent.55–58

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100 World
precancerous lesions and invasive cancers than
Low screening with Pap smears9,10 has been translated into
Medium new national and international recommendations to use
High
80 Very high validated HPV assays as the preferred test for primary
screening.11,12,60 Moreover, HPV testing can be done on
Cases per 100 000 women-years

specimens taken by the woman herself, offering

60 opportunities—in both resource-rich and poor
countries—to reach women who otherwise would not
participate in screening by enabling self-sampling.61
40 Additionally, systematic reviews of randomised trials
completed with observational data from vaccination
programmes have shown the protective effect of HPV
20 vaccines against HPV infection and associated
precancers, particularly among girls and young women
not yet infected with HPV vaccine types.3,62 Although
0 some indicative observations of a reduced incidence of
0 10 20 30 40 50 60 70 80 90
cervical cancer in vaccinated populations exist,63,64 it is
Age (years)
still too early to observe a clear vaccination effect on the
Figure 5: Age-specific incidence of cervical cancer worldwide and in terms of the four-tier HDI existing HPV-related cancer incidences.
The four tiers of HDI are the following: very high (HDI ≥0·8), high (HDI <0·8 to ≥0·7), medium (HDI <0·7 to ≥0·55), The availability of these new powerful tools for primary
and low (HDI <0·55). HDI=Human Development Index.
and secondary prevention and the enduring large burden
of cervical cancer worldwide have motivated WHO to
Although the number of certified cancer registries and initiate an ambitious plan to eliminate cervical cancer as a
the quality of registered incidence and mortality data public health problem in the 21st century by reducing the
have improved over time, only 24% of countries provided global annual age-standardised incidence to 4 per
directly usable national incidence data and 44% did so for 100 000 women.65 By vaccinating 90% of all girls by the age
mortality data (appendix pp 5–6). No information could of 15 years, screening 70% of women twice in a life time
be identified for incidence in 32 countries and for (at ages 35 years and 45 years) with a precision test (ie, a
mortality in 84 countries, thus estimates have been validated HPV assay), and treating 90% of precancerous
computed either from modelling or from neighbouring cervical lesions detected during screening, this WHO goal
countries. The GLOBOCAN 2018 estimations can be might become possible to reach.66 In several higher-
considered the best possible given the data available; resource countries, including the USA, Australia,
however, they should be interpreted with caution, New Zealand, Turkey, and several western European
because their reliability is determined by the quality and nations, HPV-based screening, combined with or without
completeness of registration and by the appropriateness cytology, are being implemented, with several countries
of external data in the absence of recorded data.17 including options to offer self-sampling kits.61 In 2018,
A key concern in comparative assessments of cervical only a quarter of 10-year-old girls globally live in the
cancer mortality is the accuracy of cause of death 85 countries that have introduced HPV vaccination. This
certification, because a large proportion of deaths are proportion varies between 13% in low-resource countries
assigned to uterine cancer without specification of exact to 82% in high-resource countries.67,68 Mathematical
topographic origin. Countries with a very high burden of modelling, using previous GLOBOCAN estimates,
cervical cancer often correspond to areas where local data predicts that the WHO threshold of 4 per 100 000 women-
are either absent or of suboptimal quality (appendix years could be reached in very high HDI areas by 2055–59,
pp 5–6). Local difference in the practice of hysterectomy whereas in low HDI countries, the elimination goal could
might have some effect on cervical cancer incidence be reached closer to the end of this century.66
reported in our study, but could not be accounted for.59 Several new assays allowing point-of-care HPV testing
Finally, we note that the successive iterations of or visual devices with automated interpretation of
GLOBOCAN present contemporary estimate of the cervical images that are accurate, robust, user-friendly,
global burden of cancer by use of the best available and affordable (which are being developed) need urgent
sources; however, they are not a good basis for time trend validation and should be manufactured at large scale if
analyses. To assess temporal aspects and, particularly, evaluations are successful.69–71 Additional implementation
the effects of interventions, the use of long-term time research and actions are needed to inform on best
series from high-quality registries is recommended, such evidence-based practices that fit various situations. These
For the Cancer Incidence in Five as those compiled in successive editions of Cancer areas include how to best integrate policies of vaccination
Continents see http://ci5.iarc.fr Incidence in Five Continents. and screening, including the screening of high-risk
Accumulated evidence indicating that screening with populations with elevated HIV prevalence; the risk-based
HPV tests is more effective in preventing future cervical management of women positive for high-risk HPV by

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use of appropriate triage procedures or through screen- 3 Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic
and-treat approaches; and adapting screening policies in vaccination against human papillomaviruses to prevent cervical
cancer and its precursors. Cochrane Database Syst Rev 2018;
settings where cervical cancer risk is low because of 5: CD009069.
successful prevention strategies. Other key issues 4 de Sanjose S, Quint WG, Alemany L, et al. Human papillomavirus
warranting further study are assessing the effect of self- genotype attribution in invasive cervical cancer: a retrospective
cross-sectional worldwide study. Lancet Oncol 2010; 11: 1048–56.
sampling kits in yielding improved participation in the 5 Bzhalava D, Guan P, Franceschi S, Dillner J, Clifford G.
target populations; strategies ensuring high compliance, A systematic review of the prevalence of mucosal and cutaneous
with treatment of precancer lesions with safe and human papillomavirus types. Virology 2013; 445: 224–31.
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efficacious procedures;60,72 and assessing the level of against infection and intraepithelial neoplasia in women.
access to treatment and palliative care centres among N Engl J Med 2015; 372: 711–23.
patients with invasive tumours.73–75 7 IARC. Cervix cancer screening—IARC handbooks of cancer
Cervical cancer kills approximately 300 000 women and prevention, vol 10. Lyon: IARC Press, 2005.
8 de Kok IM, van der Aa MA, van Ballegooijen M, et al. Trends in
affects nearly 600 000 women yearly, particularly middle- cervical cancer in the Netherlands until 2007: has the bottom been
aged women and those living in lower-resource settings. reached? Int J Cancer 2011; 128: 2174–81.
However, most cervical cancers and related deaths can be 9 Arbyn M, Ronco G, Anttila A, et al. Evidence regarding human
papillomavirus testing in secondary prevention of cervical cancer.
avoided by integrated HPV-based screening and Vaccine 2012; 30 (suppl 5): F88–99.
vaccination. WHO is developing a global plan of action to 10 Ronco G, Dillner J, Elfström KM, et al. Efficacy of HPV-based
engage stakeholders and mobilise resources to make screening for prevention of invasive cervical cancer: follow-up of four
European randomised controlled trials. Lancet 2014; 383: 524–32.
cervical cancer a rare disease globally through an
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ambitious scale-up of national services over the next United States, 2019: A review of current American Cancer Society
decades. The GLOBOCAN 2018 figures presented in this guidelines and current issues in cancer screening. CA Cancer J Clin
2019; 69: 184–210.
study are pivotal to provide a baseline for the targets of the
12 von Karsa L, Arbyn M, De Vuyst H, et al. European guidelines for
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Contributors
13 WHO. WHO Director-General calls for all countries to take action
MA developed the study design; did the statistical analyses; prepared the to help end the suffering caused by cervical cancer. 2018.
tables, figures, and maps; and wrote the manuscript. JF and FB compiled https://www.who.int/reproductivehealth/call-to-action-elimination-
the database of GLOBOCAN 2018 and subtracted data for cervical cancer cervical-cancer/en/ (accessed Oct 31, 2019).
and all cancers, provided data for the ranking of cervical cancer, and 14 WHO. 2008–2013 action plan for the global strategy for the
contributed to the material and methods. LB compiled data on HPV prevention and control of noncommunicable diseases. Geneva:
prevalence by subcontinent. EW, LB, SdS, MS, JF, and FB contributed to World Health Organization, 2008.
and critically revised the manuscript. All authors approved the final 15 de Sanjosé S, Diaz M, Castellsagué X, et al. Worldwide prevalence
submitted version. and genotype distribution of cervical human papillomavirus DNA
in women with normal cytology: a meta-analysis. Lancet Infect Dis
Declaration of interests
2007; 7: 453–59.
MA’s institute received financial support from the Belgian Cancer
16 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.
Foundation through the IHUVAC project. The institutions of MA and
Global cancer statistics 2018: GLOBOCAN estimates of incidence
LB received support from the DG Research and Innovation of the and mortality worldwide for 36 cancers in 185 countries.
European Commission. LB’s institute received unrestricted grants from CA Cancer J Clin 2018; 68: 394–424.
Glaxosmithkline and Merck Sharp & Dohme. EW, LB, SdS, MS, JF, and 17 Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global
FB declare no competing interests. cancer incidence and mortality in 2018: GLOBOCAN sources and
Acknowledgments methods. Int J Cancer 2019; 144: 1941–53.
MA was supported by the Horizon 2020 Framework Programme for 18 Arbyn M, Raifu AO, Weiderpass E, Bray F, Anttila A. Trends of
Research and Innovation of the European Commission, through the cervical cancer mortality in the member states of the European
RISCC Network (grant 847845). Where authors are identified as Union. Eur J Cancer 2009; 45: 2640–48.
personnel of the International Agency for Research on Cancer or WHO, 19 Loos AH, Bray F, McCarron P, Weiderpass E, Hakama M,
Parkin DM. Sheep and goats: separating cervix and corpus uteri
the authors alone are responsible for the views expressed in this article
from imprecisely coded uterine cancer deaths, for studies of
and they do not necessarily represent the decisions, policy or views of the
geographical and temporal variations in mortality. Eur J Cancer 2004;
International Agency for Research on Cancer or WHO. The findings and 40: 2794–803.
conclusions in this report are those of the authors and do not necessarily
20 Dyba T, Hakulinen T. Comparison of different approaches to
represent the official position of the Centers for Disease Control and incidence prediction based on simple interpolation techniques.
Prevention. This manuscript is based on research funded in part by the Stat Med 2000; 19: 1741–52.
Bill & Melinda Gates Foundation. The findings and conclusions 21 UN Development Programme. Human development report 2016:
contained within are those of the authors and do not necessarily reflect human development for everyone. 2016. http://hdr.undp.org/sites/
positions or policies of the Bill & Melinda Gates Foundation. The Bill & default/files/2016_human_development_report.pdf (accessed
Melinda Gates Foundation is acknowledged for funding the free open Sept 12, 2019).
access to this publication. Koen de Visscher is acknowledged for the 22 Waterhouse JAH, Muir CS, Shanmugaratnam K. Cancer incidence
production of EPS files of the figures. in five continents, 4th edn. Lyon: International Agency for Research
on Cancer, 1976.
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