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Global burden of cervical cancer and
World Health Organization priorities
Rolando Herrero
Cervical cancer: risk factors
• Multiparity
• Early age at sexual debut/marriage
• Early age at first pregnancy
• Smoking
• Oral contraceptives use
• Cervical inflammation
• HIV infection/immuno-suppressed status
Cervical cancer: Cause
•
Persistent infection with one of 13 oncogenic HPV
(16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68)
types is the necessary cause
•
Not everyone infected with HPV will develop cervical
cancer
•
80% of HPV infections regress within two years
•
Cervical cancer is a very rare long-term outcome of a
common infection
•
1 out of every 10,000 women infected with high-risk
HPV will develop cervical cancer in their life-time
Natural history of cervical cancer
HPV infection
Co-factors
Normal cell
Persistent
HPV infection
Integration
of viral DNA
Transformation
of cell
Dyplasia
Cancer
Global burden of cervical cancer
World
2012 (ASR)
2030
Incidence
528 000 (14.0)
710 000
Mortality
266 000 (6.8)
383 000
5 year Prevalence
1 547 000
-
Less developed regions
2012 (ASR)
2030
Incidence
445 000 (15.7)
648 000
Mortality
230 000 (8.3)
363 000
5 year Prevalence
1 258 000
Asia
2012 (ASR)
2030
Incidence
284 823 (12.7)
391 042
Mortality
144 434 (6.4)
217 890
5 year Prevalence
806 000
-
Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC
CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.
Available from: http://globocan.iarc.fr, accessed on 05/05/2015.
Cervical cancer in the World
• Fourth-most common cancer
in women
• 528,000 new cases in 2012
• 266,000 deaths
• Around 85% of the global
burden occurs in the less
developed regions
Source: Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and
Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon,
France: International Agency for Research on Cancer; 2013.
Available from: http://globocan.iarc.fr, accessed on 17/02/2014.
SOURCE: Forman et al., (2013) Cancer Incidence in
Five Continents, Vol. X (electronic version) Lyon,
IARC. http://ci5.iarc.fr last accessed on 18/02/2014.
Trends in Incidence & Mortality from
cervical Cancer - England
Source: UK Cancer Information Service 2012
Trends in cervical cancer incidence in selected low- and middleincome populations (1960-2007)
Cancer Incidence in Five Continents Volumes I to X
(electronic version) Lyon, IARC. http://ci5.iarc.frc
Cervical Cancer Incidence – Trends in Europe
Cervical cancer mortality in selected Latin American Countries
(1955-2012)
18
16
14
12
10
8
6
4
2
0
Mexico
Chile
Uruguay
World Health Organization, mortality database
http://www.who.int/healthinfo/statistics/mortality_rawdata/en/i
ndex.html (accessed on 02/03/2015)
Cervical cancer mortality by level of
education 1990-2005
Age‐adjusted rates per 100,000 women
Ferreccio Int J Cancer 2012
WHO priorities for cervical cancer
control
WHO priorities for cervical cancer control
• Socio-economic development
• Women’s empowerment
• HPV vaccination of adolescent girls
• Screening programs with new technologies
• Early diagnosis and treatment
• Palliative care
Recent knowledge of natural
history and biology of HPV
infection and cervical cancer have
resulted in new primary and
secondary prevention methods
Newly available primary and
secondary prevention tools
• HPV vaccination of adolescents
• Modified schedules <3 doses
• HPV testing of women over 30 years old
• Self collection
• CareHPV
• Visual inspection with acetic acid
• See and treat
New Tools for Cervical cancer
prevention: HPV Vaccines
•
•
•
•
•
Prophylactic vaccines could prevent 70-90% of
cervical cancers, multivalent even more
Programs already in place in most developed countries
Poorest countries US$ 4.50 per dose (GAVI).
GAVI aims to support HPV vaccination for 30 million
girls by 2020.
Many challenges remain:
• Organizing HPV vaccination programmes for adolescent
• Obtaining high coverage in the target group
• Affordability and sustainability of programs
Secondary prevention is still needed
•
•
•
Worldwide coverage of targeted adolescent girls by HPV
vaccines will take many years
Impact on ICC incidence is expected several decades
after vaccination
Even in the most optimistic scenario where vaccination
coverage in the target age group would reach 100%
within the 10 coming years in all countries of the world,
it is estimated that nearly 28 million women will be
affected by cervical cancer in the coming 40 years1.
1
Globocan, Ferlay
et al., 2012
Some reasons for limited impact of
cervical cancer screening
•
•
•
•
•
•
•
•
Poor screening coverage
Specimen collection and handling
Inherent limitation of cytology
Lack of SOPs and quality assurance at the labs
Loss to follow-up
Lack of information systems
Geographic and economic barriers
Lack of organization of program
Characteristics of HPV testing
Advantages
Objective
Robust
Reproducible
Accurate
Effective
Extension of intervals
Self-collection
OK for post vaccination
Disadvantages
Limited specificity
High cost
Follow up of positives
Technical requirements
Social stigma
20
Research gaps
•
Few randomized trials that
evaluated screen-and-treat
strategies and patient-important
outcomes.
•
Very few studies that assessed
the strategies that the guideline
development group ranked as
clinically relevant (e.g. HPV test
followed by VIA).
21
Key research questions identified
during WHO guidelines
development
• HPV testing followed by treatment
• Strong recommendation, weak evidence
• The Expert Committee concluded that this approach
needs to be better understood: benefits and harms
• HPV testing + triage
• Which triage test?
• Which algorithm?
• Which algorithm for which context?
IARC research projects on screening:
• CESTA:
• Providing evidence for the main
recommended Screen & Treat algorithms
from the updated WHO guidelines
• targeting low-income countries (LIC)
• ESTAMPA:
• HPV triage in programmes with HPV
primary testing
• Targeting middle-income countries (MIC)
Conclusions
• Cervical cancer remains an important
public health problem in developing
countries
• New opportunities for prevention are
very promising
• WHO can play an important role in
implementation of programs to assure
success