Transcript PREVENTION OF CERVICAL CANCER

DR EMAGBETERE O .A (MBBS, FMCOG, FWACS)
PRETEST
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Answer true or false
Cervical cancer is a sexually transmitted disease.
Lack of basic health education is a serious contributor to
cancer of cervix(ca cervix) occurrence.
Health practitioners and government contribute to high
incidence of ca cervix in Nigeria.
About 25% of women will be infected with Human
pappiloma virus at some point in their lives
Vaccination alone is the only effective way of preventing ca
cervix.
Cervarix is a highly effective vaccine against HPV 11, 16 and 18
OUTLINE
 Introduction
 Causes of cancer increase
 Cervical screening
 Prevention
 Human papilloma virus
 HPV vaccines
Introduction
 Disease of inequity
 Second most common cancer among
women worldwide, with about 493,000 new
cases diagnosed annually.
 274,000 deaths due to cervical cancer each
year.
 >80% occur in developing countries.
 Expected to increase to 90% by 2020(1).
 It is the largest single cause of years of life
lost to cancer in the developing world(2)
(1)Parkin DM, Bray F. Chapter 2: the burden of HPV-related cancers.
Vaccine 2006;24:Suppl 3:S11-S25
(2) Agosti JM, Goldie SJ. Introducing HPV Vaccine in Developing Countries — Key Challenges and Issues
NEJM 2007;356:1908-1910
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New Cases - 2002 - Selected African Countries
9,922
10,000
9,000
7,619
7,515
8,000
6,742
New Cases
7,000
6,000
5,000
3,709
4,000
2,713
2,429
3,000
2,000
1,000
0
Nigeria
RSA
Egypt
SOGON 2007
CITY
Congo
Tanzania
Country BENIN
Uganda
Ethiopia
Global Cervical Cancer Incidence
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Comparison of Mortality due to
Cancer vs. Infectious Diseases
SOGON 2007
BENIN CITY
Projected Evolution of Cancer Cases
SOGON 2007
BENIN CITY
REASONS FOR CANCER INCREASE
IMMUNOSUPPRESION
Associated with the persistent of HPV infection &
may hasten the journey to carcinoma in-situ
 HIV/AIDS pandemic in Africa
 Poverty – Many live on < 1$ a day!
 Sexual networking (?) – effects from other STIs
Schiffman et al 2007 – Lancet,370:890 – 907
Chama et al 2005, J Obstet Gynecol 25(3):p286-8.
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Lack of political will/Commitment
“Women are dying not just because we do not
understand the cause but we have not consider their
lives worth saving…”
Mahamud Fathalla – Former FIGO president
Many African Leaders of head of states do not have
concrete plans for genital cancer screening – e.g.
Nigeria has no national programme in place not to
mention the poorer and war torn countries!
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POOR HEALTH SEEKING BEHAVIOUR
Belief that health institution needs to be
visited only when one is sick negates
screening opportunities.
Women in our continent typically do not
receive care until their disease is well
advanced, it is usually fatal
Visit at least a native practitioner
Apathy of Men to women’s health issues.
Lack of economic empowerment of
women.
80% present late
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Lack of Awareness and Knowledge
 women lack basic health education
 Some women do not know the importance of a
pap smear test,
 find them embarrassing or even traumatic, and in
part this may explain why screening fails to reach
everyone who is at risk
 Health practitioners underestimate level of risk
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Weak Health Systems
 little existing public health infrastructure
 A 2001 study by the World Health
Organization found no organized cervical
cancer screening programs in many Latin
American countries, any of the high-risk
Sub-Saharan African countries or India
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Poverty
 Pap smears are expensive, costing about (US$9) each,
and any abnormality detected requires referrals and
follow-up which, according to Prof Helen Rees,
executive director of the Reproductive Health and HIV
Research Unit at the University of Witwatersrand,
"don't always happen when services are overstretched
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Poverty Index: % Living below Poverty Line.
Country
Percentage
Nigeria
70.8
Ghana
44.8
Zambia
75.8
South Africa
10.7
Rwanda
51.7
Tunisia
< 2.0
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Cervical Cancer:
A Failure of Screening !
 Failure to be screened: 50 – 60 %
 Ever
 At an appropriate interval
 Failure of screening: 40 –50%
 Screening did not show an abnormality
False negative
 Interpretation error
 Smear takers error
 Failure to follow up on recommendations of screening
program: 10 – 20 %
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WHY IS IT PREVENTABLE ?
 Sexually transmitted malignancy: HPV 16,
18 & others
 Window of opportunities
.Premalignant latency period
.Comparatively slow growing
.Screening extremely cost effective
.Cure of premalignant lesion realizable
 Availability of the vaccine
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PREVENTIONS
 Primary Prevention
Risk reduction
 Condom use
 Circumcision
 Vaccine
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 Secondary Prevention

Screening
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PRIMARY PREVENTION
 OBSTACLES
 Difficult to change
 Cultural
practices
 Costly
 Political
 Religious
 Lack
of awareness
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behaviour
SECONDARY PREVENTION
 Methods of screening
 Pap smear
 HPV DNA testing
 Liquid cytology/Thin prep
 Visual inspection of cervix using acetic acid
 VILI
 MVIA
 Cervicograms
 Polarprobe
 Optical Technologies
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SECONDARY PREVENTION
 Drawbacks
Cost
 Need for specialized skilled personnel
 Need for functional laboratories
 Follow-up schedules
 Lack of resources
 Sensitivity/Specificity
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What does a Pap smear test involve?
 vaginal speculum exam during which
a sample of cells from a woman’s
cervix using a small flat spatula or
brush.
 Smearing and fixing cells onto a glass
slide.
 Sending the slide to a cytology
laboratory where it is stained and
examined under a microscope to
determine cell classification.
 Transmitting the results back to the
provider and then to the woman.
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Specimen Preparation for Clinical CytoPathology (Pap Smears)
Transfered on the slide
(Fixation)
Spatula-CytoBrush
Papanicolaou
staining
Pathology Review
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Strengths of cytology:
 Historical success in developed countries.
 High specificity, meaning women with no
cervical abnormalities are correctly
identified by the test with normal test
results.
 A well characterized screening approach.
 May have the potential to be cost-effective
in middle-income countries.
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Limitations of cytology:
 Moderate to low sensitivity:
 High rate of false-negative test results
 Women must be screened frequently
 Rater dependent
 Requires complex infrastructure
 Results are not immediately available
 Requires multiple visits
 Likely to be less accurate among post-menopausal
women
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Assessment Newer Technologies
 Fluorescence and reflectance spectroscopy for realtime screening and diagnosis
 Quantitative cytology for objective, real-time
screening (Hybrid Capture, HPV DNA, mRNA)
 Quantitative histo-pathology to relate optical
measurements to a quantitative model of progression
 Confocal Microscopy and In Vivo Confocal Endocopy
 Visual Inspection( ACA/LI)
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New version of the CytoSavant : works with
H@E stained specimen
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Specimen Preparation for Quantitative Cytology (Thin-Prep)
Spatula-CytoBrush
PreservCyt solution
CytoSavant Automatic Scanning
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ThinPrep ® Processor
Feulgen-Thionin Staining
Multi-spectral digital colposcopy
 Multi-spectral digital colposcopy is a
technology unlike the probe in that the
device has no contact with tissue and takes
an image of the entire cervix.
 The device consists of white, green, and blue
light. The green light fluoresces blue and
the blue light fluoresces green.
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Fluorescence Spectroscopy
 Fluorescence and reflectance spectroscopy
have been shown to differentiate
precancerous and normal tissues.
 Using a point probe that interrogates a 2mm
area, it has demonstrated increased
sensitivities and specificities respectively.
 A diagnostic trial in which all measured
sites were biopsied reveals a sensitivity and
specificity of 80% and 70% using a variety of
algorithmic approaches
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Patient 5
SOGON 2007
CITY
BENIN
Patient 9
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Human Papilloma Virus
The Necessary Cause Abounds
 Genital HPV is an extremely common viral
infection. (Of the more than 100 known HPV
strains, 30 are sexually transmissible and are
considered genital HPV.)
 Up to 80% of women will be infected with HPV at
some point during their lives
 The vast majority of cases are transient: The body's
immune system fights off the infection, which
then either becomes inactive or resolves on its
own.
 Why does it persist in some individuals?
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Five Most Common HPV Types in
Invasive Cervical Cancer by Region
All Cases
40
40
20
20
0
0
18
33
HPV Type
45
40
71.8%
16
31
Asia
60
%
%
70.4%
16
Africa
60
66.9%
20
0
33
HPV Type
45
35
31
45
Europe
40
73.8%
20
0
16
18
58
HPV Type
33
52
16
North American and Australia
18
33
HPV Type
South and Central America
60
60
40
75.8%
%
%
18
60
%
%
60
20
0
40
65.1%
20
0
16
18
31
HPV Type
Smith et al. Unpublished
45
33
16
18
31
HPV Type
45
33
HPV: a challenge for the immune system
HPV is designed to evade the natural immune
defense mechanisms:

No viraemia

HPV does not kill keratinocytes:
 no
inflammation
 no pro-inflammatory cytokines
 poor activation of epithelial APCs
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Natural History of HPV Infection:
Surrogate Markers for Cervical Cancer
0 to 5 Years
Persistent
Infection
Initial
HPV
Infection
Up to 20 Years
CIN 2
CIN 3
Sq. Cell
Carcinoma
AIS
AdenoCarcinoma
CIN 1
Basis for Licensure/Cancer
Efficacy:
Cleared HPV Infection
Demonstrate Prevention of
HPV 16/18-CIN 2/3 + AIS
HPV Vaccine Development
• Creation of virus-like particles (1991)
• Mimic natural virion structure
•Generate potent immune response
• Contain no DNA
•**Non-infectious
•**Cannot cause disease
L1
L1
L1
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SOGON 2007
BENIN CITY
GARDASIL in Summary
**Studies conducted in >27,000 subjects in 33 countries
 GARDASIL is well-tolerated and safe
 GARDASIL is highly effective at prevention of:
 Persistent infection with HPV types 6/11/16/18
 Clinical disease caused by HPV types 6/11/16/18
 Protection appears to be durable, with stable
antibody levels for at least 3.5 years post
immunization
 GARDASIL is a prophylactic vaccine and does not
treat disease or infection with HPV
 GARDASIL does not replace screening
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CC is a critical public health problem
 GSK cervical cancer vaccine (Cervarix™) is highly
protective against HPV-16/18 CIN2+ in a broad
population of women aged 15-25 years.
 GSK cervical cancer vaccine (Cervarix™) is very
immunogenic in women aged 10-25 years.
 GSK cervical cancer vaccine (Cervarix™) is generally
safe and well tolerated in the current clinical program,
with pain at injection site being the most frequently
reported symptom.
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Making Cervical Cancer History
Public health partners need to pursue a highly
collaborative program of global HPV vaccination and
screening to limit the impact of the second leading
cause of cancer in women worldwide—a cancer that
should now be largely preventable
 Effective collaboration predicated on shared vision,
trust and commitment to advocacy for global cervical
cancer control
 Funding to support vaccination and screening
programs
 Research to guide optimal implementation strategies
 Realistic efforts by all partners to share or mitigate risk
 Achievement of, and action on, common vision of
optimal product profiles, vaccine demand forecasts and
sustainable introduction strategies
CAPITOL HILL CLINIC/HOSPITAL

POST TEST






Answer true or false
Cervical cancer is a sexually transmitted disease.
Lack of basic health education is a serious contributor to ca
cervix occurrence.
Health practitioners and government contribute to high
incidence of ca cervix in Nigeria.
About 25% of women will be infected with Human
pappiloma virus at some point in their lives
Vaccination alone is the only effective way of preventing ca
cervix.
Cervarix is a highly effective vaccine against HPV 11, 16 and 18