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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
UICC
HPV and
CERVICALCANCERCURRICULUM
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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01 Chapter 5.
Application of HPV vaccines
Prof. Suzanne Garland MDDirector of Microbiological Research
Director of Clinical Microbiology and Infectious DiseasesThe Royal Women's Hospital
Melbourne, Australia
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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02Selection of the right age group
for vaccination
Genital HPV infections are common sexuallytransmitted infections
- Readily transmissible: within few months of start of sexual activity
- Cumulative lifetime risk of infection = 50-80%
- Cumulative lifetime exposure to HPV 16 and/or HPV 18 20%1
Natural history of HPV- Most HPV infections are transient: the majority of young women
clear HPV infection within 1-2 years 2
HPV type prevalence
- HPV prevalence among different populations of women range
from 2-44%, with worldwide overall prevalence of 10.4%- Age dependent
- Different profiles in different countries 3
1 Baseman J et al. Clin Virol 2005;32:16-24.2 Sankaranarayanan R et al. Vaccine 2008; 26: Suppl 12:M43-52.3 de Sanjos S et al. Lancet Inf Dis 2007;7:7 453-459.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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03Selection of the right age group
for vaccination
Antibody responses in known age groups Antibody responses have been used as a surrogate to
bridge efficacy against cervical and/or vaginal disease in: 1-3
- Young women
- Pre-adolescence
- Mature women
Basis for registration 4
1 Munoz N et al. Lancet 2009;373:1949-57.2 Block SL et al. Pediatrics 2006;118(5):2135-45.3 Pedersen C et al. J Adolesc Health 2007;40(6):564-71.4 Skinner SR et al. Med J Aust 2008;188(4):238-242.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
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Efficacy against HPV vaccine-related disease correlateswith the presence of serum antibodies 1-4
Recipients show rapid development of high titre (many
fold greater than natural infection)
Currently no identified correlate of protection
Immune responses are age-dependent 5,6
Selection of the right age group
for vaccination
1 Harper et al Lancet 2006:1247-55.2 Villa LL et al Brit J of Cancer 2006;95(11):1459-66.3 Villa LL et al. Vaccine 2006;24:4931-39.4 Harper D et al. Gynec Oncol 2008;109(1):158.5 Block SL et al. Pediatrics 2006;118(5):2135-45.6 Pedersen C et al. J Adolesc Health 2007;40(6):564-71
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
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05
Dependent on age of sexual debut (culture-dependent):
age of sexual debut is decreasing over time in some
countries, but this trend is less pronounced and less
widespread than sometimes supposed 1
Prophylactic HPV vaccines are licensed for the ages of 9
to 12 years in many countries
Selection of the right age group
for vaccination
1 Wellings K et al. Lancet 2006; 368:1706-28
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Needs to be practical for vaccine delivery
- School-based programmes
- Adolescent health programme focus
- Practitioner-based programme
Collaborate with already existing childhood extendedimmunisation programmes (EPI)
- Maximise implementation using already established
vaccination infrastructure
Selection of the right age group
for vaccination
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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07 HPV vaccination in boys?
Clinical trials in boys
- Immunogenicity has been shown with both vaccines 13,14
- Preliminary results are available showing protection from
infection and external genital warts for the quadrivalent
vaccine 15
Cost-effectiveness?
Would allow destigmatisation of females
Herd immunity: effect on females with lower uptake of
vaccine
13 Reisinger KS et al. Pediatr Infect Dis J. 2007 Mar;26(3):201-9.14 Petj T et al. J Adolesc Health. 2009 Jan;44(1):33-40.15 Palefsky J. Eurogin February 2010.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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08Does prophylactic vaccination replace
cervical screening?
Efficacy following three doses of vaccine for those nave
to vaccine-related HPVs is nearly 100% 16-18
About 30% of cancers are caused by non-vaccine related-
HPVs
- Immunity largely type-specific
Some cross-protection to HPV types phylogenetically
related to HPV 16 and HPV 18
16 Garland SM et al. NEJM 2007;356:1928-1943.17 FUTURE II SG. NEJM 2007;356:1915-1927.18 Paavonen J et al. Lancet 2007;369:2161-2170.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
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09
Some form of screening is still required
Challenges with an implemented vaccine programme: 19
- Screening sensitivity and positive predictive value for
high-grade lesions will be reduced with vaccination
- Reduced future cancer burden through primary
prevention, cervical screening programmes will be much
less cost-effective
- Vaccinees may be unclear as to the need for Pap test
Does prophylactic vaccination replace
cervical screening?
19 Cuzick et al. Vaccine 26S; 2008: K29-41.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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10Vaccinating sexually active women: is
prior HPV DNA testing mandatory ?
From a public health point of view, this is not
recommended
- A negative test does not tell you whether a woman has
previously been infected
- A positive test could be a newly acquired infection or a
persistent infection- More likely negative if transient infection
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
Slide
11Vaccinating sexually active women:
measure antibodies before vaccinating?
HPV antibodies
- A poor marker of past or present infection, ~ 60% of
those HPV DNA-positive have a measurable serological
response 20
- Serological responses are slow (take up to 12-18
months post-infection)- No reliable diagnostic assays exist
- Assays need to be standardised 21
20 Carter JJ et al J Infect Dis 2000, 181,1911-1919.21 Pagliusi SR, Garland SM. Molecular Markers 2007;9(32):1-14.
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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12Opportunities for HPV vaccination in
low-resource countries
GAVI-subsidized childhood vaccination programmes for
72 countries (late 2008/early 2009)
Need for similar GAVI endorsement of HPV vaccines
Reduced pricing of HPV vaccines for poorer countries
- Accelerated Development and Introduction Plans
(ADIPs)
- Mechanisms such as the Advanced Market Commitment
(AMC)
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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13Are three injections mandatory for
efficient protection?
Very limited data on prevention of infection or disease with
two-dose schedule
- High compliance of study participants to three-dose
schedule
Given the nature of the vaccine, likely that three doses will
be required as with HBV Studies to evaluate modifications to current vaccine
schemes are ongoing
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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14Vaccine effectiveness: need for
ongoing surveillance
HPV genotyping
- Prevalence: normal cytology, cervical dysplasia/cancer
- Vaccine-related type prevalence change?
- Protection against phylogenetically related non-vaccine
types?
- Replacement of vaccine HPV types?
- HPV serosurveillance
Genital wart surveillance (females and males)
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
Slide
15Putting all the pieces together: HPV
vaccination programme in Australia
Australia was the first country to implement a national
vaccine programme funded by the government
Vaccination in both girls and boys
Included a catch-up programme in women
Cervical screening programme already in progress
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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16The Australian National HPV
Vaccination Programme (1)
November 2006
- Commonwealth Minister for Health announced funding
for HPV vaccine (Gardasil)
April 1st 2007
- Added to National Immunisation Programme on an
ongoing basis for 12-13 year-old girls via schools
July 2007 December 2009
- Two-year catch-up programme for 12-26 year-old
females
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
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17The Australian National HPV
Vaccination Programme (2)
Three components:
Ongoing school-based programme
1. Girls aged 12-13 years (first year of high school)
Two-year catch-up programme to 2009
2. Girls/adolescent females aged 12-18 years
- School-based +/- community-based mop up
3. Young women aged 18-26 years
- General practitioners and other community-based
services
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccines
Prof. Suzanne Garland MD
Slide
18The Australian National HPV
Vaccination Programme (3)
Vaccination coverage (by the end of May 2009)
- 5 million doses of the vaccine distributed (~80%) first
years cohort
- ~60% coverage of the eligible population in the catch-up
group of young females
- Rural areas: 70% of target age groups received firstdose
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesProf. Suzanne Garland MD
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19Community-based programme:
18-26 year-olds
Difficult demographic to ensure completion of 3-dose
vaccine schedule
Implementation strategy:
- Motivate and empower young women to protect
themselves
- Support GP clinics to run pro-active vaccinationcampaign
- High-profile advertising and public relations campaign
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesProf. Suzanne Garland MD
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20National HPV Vaccination Register
National HPV Vaccination Register launched by the
Australian Government (VCCR)
- Collect information on vaccination programme
- Evaluate impact of vaccination on cervical abnormality
and cancer rates by matching with Pap test registers
Document doses of HPV vaccine and dates administered
- Assess age-specific coverage achieved
- Contact if booster doses required
- Link to Pap Screen registers
- Evaluate the impact of the vaccine on cervical cancer
Providers must report vaccination in 12-18 year age group
- Victorian councils using Immunisation Provider System
(ImPS) to collect data
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesProf. Suzanne Garland MD
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21Lessons learned, future directions
and challenges
Opportunities to link the National HPV vaccine Register
with:
- Cervical cytology screening registers
- HPV genotype prevalence surveillance pre- and post-
vaccine implementation
- Ultimately cancer registers for ongoing surveillance
Communication, feedback, goodwill, etc.
Vaccine effectiveness
Evaluation of cervical screening practices
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesProf. Suzanne Garland MD
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22Lessons learned, future directions
and challenges
Approaches for implementation of HPV vaccination
programmes are different between countries
Australia, UK, Canada: successful public-sector HPV
vaccination programmes primarily based on school-based
provision, and largely covered by public sector funds for
all age-eligible female adolescents 1-3
Resulted in relatively high rates of HPV vaccination
coverage: e.g. Australia coverage up to 80% 2,3
1 Shefer et al. Vaccine 2008;26(Suppl 10):K68-752 Brotherton JM et al. Commun Dis Intell 2008;32:457-613 Garland SM et al. Vaccine 2008;26(Suppl 12):M80-8
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesProf. Suzanne Garland MD
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23Challenges and future directions
Largely vaccinated cohort of Australian women
Review and re-engineer National Cervical Screening
Programme (NCSP) introduced in 1991
NSCP currently recommends cervical cytology screening
for all women who have ever had sex
- Start at 18-20 years or 1-2 years after start of sexualintercourse, which ever is later
- Repeat Pap smear every 2 years
- Screening ends at age 70 if 2 normal Pap smears within
last 5 years
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UICC HPV and Cervical Cancer CurriculumChapter 5. Application of HPV vaccinesP f S G l d MD
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24
Thank you
This presentation is available atwww.uicc.org/cervicalcancercurriculum