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UICC HPV and Cervical Cancer Curriculum Chapter 5. Application of HPV vaccinesProf. Suzanne Garland MD

UICC

HPV andCERVICALCANCERCURRICULUM


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01 Chapter 5.

Application of HPV vaccines

Prof. Suzanne Garland MDDirector of Microbiological Research

Director of Clinical Microbiology and Infectious Diseases

The Royal Women's Hospital

Melbourne, Australia


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02Selection of the right age group

for vaccination

• Genital HPV infections are common sexually

transmitted 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 Sanjosé S et al. Lancet Inf Dis 2007;7:7 453-459.


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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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04

• Efficacy against HPV vaccine-related disease correlates

with 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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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


for vaccination

1 Wellings K et al. Lancet 2006; 368:1706-28


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06

• Needs to be practical for vaccine delivery

- School-based programmes

- Adolescent health programme focus

- Practitioner-based programme

• Collaborate with already existing childhood extended

immunisation programmes (EPI)

- Maximise implementation using already established

vaccination infrastructure


for vaccination


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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 Petäjä T et al. J Adolesc Health. 2009 Jan;44(1):33-40.15 Palefsky J. Eurogin February 2010.


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08Does prophylactic vaccination replace

cervical screening?

• Efficacy following three doses of vaccine for those naïve

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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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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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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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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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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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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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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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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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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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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• Vaccination coverage (by the end of May 2009)

- 5 million doses of the vaccine distributed (~80%) first

year’s cohort

- ~60% coverage of the eligible population in the catch-up

group of young females

- Rural areas: 70% of target age groups received first

dose


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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 vaccination

campaign

- High-profile advertising and public relations campaign


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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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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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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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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 sexual

intercourse, 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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24

Thank you

This presentation is available at

www.uicc.org/cervicalcancercurriculum

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