Human Papillomavirus HPV Vaccine Background and Overview Lauri Markowitz, MD DSTDP, NCHHSTP, CDC Tit - PowerPoint PPT Presentation

1 / 47
About This Presentation
Title:

Human Papillomavirus HPV Vaccine Background and Overview Lauri Markowitz, MD DSTDP, NCHHSTP, CDC Tit

Description:

Other anogenital cancers: (anal, penile, vaginal, vulvar) ... Cervical, vaginal and vulvar precancerous or dysplastic lesions. Quadrivalent HPV Vaccine: ... – PowerPoint PPT presentation

Number of Views:331
Avg rating:3.0/5.0
Slides: 48
Provided by: univers154
Category:

less

Transcript and Presenter's Notes

Title: Human Papillomavirus HPV Vaccine Background and Overview Lauri Markowitz, MD DSTDP, NCHHSTP, CDC Tit


1
Human Papillomavirus (HPV) VaccineBackground
and OverviewLauri Markowitz, MDDSTDP,
NCHHSTP, CDCTitle X Grantee MeetingSeptember
2006
2
  • The findings and conclusions in this
    presentation have not been formally disseminated
    by the Centers for Disease Control and Prevention
    and should not be construed to represent any
    agency determination or policy.

3
Background Human Papillomavirus
  • Non enveloped DNA virus
  • gt100 different types
  • 40 types are sexually transmitted
  • Low-risk types (6,11, 42, 43, 44)
  • High-risk types (16, 18, 31, 33, 35, 39, 45,
    51, 52, 56, 58.)

4
gt100 HPV types
Cutaneous
Mucosal
(40 types)
(60 types)
Common
high-risk
low-risk
warts
types (16,18)
types (6,11)
(hands/feet)
  • low grade cervical abnormalities
  • high grade abnormalities/
  • cancer precursors
  • anogenital cancers
  • low grade cervical abnormalities
  • genital warts
  • respiratory papillomas

5
Genital HPV Infection
  • HPV is the most common sexually transmitted
    infection in the US
  • First infection is usually acquired soon after
    sexual debut. Infection with multiple types
    common
  • Infection is usually transient and not associated
    with symptoms 90 of infections clear within 2
    years
  • Persistent HPV infection is cause of cervical
    cancer as well as other anogenital cancers

6
Natural History of HPV Infection and Cervical
Cancer
Up to 20 years
1 year
Up to 5 years
Persistent infection
CIN 2/3
Initial HPV infection
CANCER
CIN 1
CLEARED HPV INFECTION
cervical intraepithelial neoplasia
7
HPV-Related Disease Burden, U.S.
  • Cervical cancer 9,710 cases 3,700 deaths (2006
    estimate)
  • 70 caused by types 16,18
  • Pap tests 50 million 2.8 million abnormal
  • Genital warts .5 to 1million
  • 90 caused by types 6,11
  • Recurrent respiratory papillomatosis (rare)
  • 90 caused by types 6,11
  • Other anogenital cancers (anal, penile, vaginal,
    vulvar)

8
Cervical Cancer Mortality Rates U.S., 1946-1984
Source Program for Improving Clinical Pap Smear
Programs and Management, Office of Population
Affairs, DHHS, 1987.
9
Most Common Cancers in Women
Less developed countries
More developed countries



Breast
Cervix
Ovary
Endometrium
Colon/rectum
Lung
Stomach
600
200
400
600
0
400
200
Annual number of cases (thousands)
Adapted from Parkin et al. Eur J Cancer 2001,
37S4
10
Percentage of Adolescents Who Have Had Vaginal
Sex, by Gender and Age National Survey of Family
Growth (NSFG), 2002
90
77
80
70
70
69
60
49
62
50
Females
40
46
Males
40
26
37
30
25
20
10
0
15
16
17
18
19
Age
Mosher et al., 2005 Vital and Health Statistics
No. 362
11
Cumulative Incidence of Any HPV Infection among
Female College Students, by Time Since Sexual
Debut
4 years, gt 50
Winer et al. Am J Epidemiol 2003,157
12
HPV Prevalence
Population Estimates, U.S.
  • 20 million people are infected
  • 15 of persons age 15-49 currently infected
  • 6.2 million new infections each year
  • gt 50 of sexually active men women acquire
    genital HPV infection

W. Cates, STD April 1999, Weinstock, Perspectives
on Sexual and Reproductive Health 2004, Koutsky
Am J Med 1997
13
Licensed Candidate Prophylactic HPV Vaccines
Types 16/18 cause 70 cervical cancer Types 6/11
cause 90 genital warts
14
Licensed Candidate Prophylactic HPV Vaccines
Advisory Committee on Immunization Practices
15
HPV VLP Vaccines
  • HPV L1 major capsid protein of the virus is
    antigen used for immunization
  • Expression of L1 protein uses recombinant
    technology
  • L1 proteins self-assemble into virus-like
    particles (VLP)

HPV VLP
16
Quadrivalent HPV Vaccine Initial Clinical Studies
  • Efficacy studies in females 16 - 26 years
  • Safety and immunogenicity studies in
  • 9 - 15 year olds

17
Quadrivalent HPV Vaccine FDA Licensure June
2006
  • Indicated in girls and women 9-26 years of age
    for the prevention of the following diseases
    caused by HPV types 6, 11, 16, and 18
  • Cervical cancer
  • Genital warts (condyloma acuminata)
  • Cervical, vaginal and vulvar precancerous or
    dysplastic lesions

18
Quadrivalent HPV Vaccine additional clinical
development
  • Efficacy trials in males
  • Efficacy trials in females older than 26 yrs
  • Long term follow-up studies

Results expected in next few years
19
Efficacy Analysis Populations for Quadrivalent
Vaccine
  • Per Protocol Population for Efficacy (PPE)
  • Received all 3 vaccinations, naïve to
    relevant vaccine HPV type through Month 7, did
    not deviate from protocol cases counted after
    Month 7.

20
Efficacy for Prevention of Clinical HPV Disease
Due to HPV 6/11/16/18 among 16-26 year-old
females
Package insert Gardasil Integrated dataset
results in the per-protocol populations CIN
cervical intraepithelial neoplasia AIS
adenocarcinoma in situ
21
Quadrivalent HPV Vaccine
  • High efficacy against outcomes due to HPV vaccine
    types among females without evidence of infection
    with the relevant HPV type
  • No evidence of efficacy against disease due to
    existing infection
  • Infection with one HPV type does not diminish
    efficacy of vaccine against other vaccine HPV
    types

22
Efficacy Analysis Populations for Quadrivalent
Vaccine
  • Per Protocol Population for Efficacy
  • Received all 3 vaccinations, naïve to
    relevant vaccine HPV type through Month 7, did
    not deviate from protocol cases counted after
    Month 7.
  • Modified Intent to Treat-Population
  • Received at least one vaccination and had any
    follow-up visit one month after dose 1. Subjects
    were included regardless of baseline HPV status.
    Cases were counted from 30 days after dose 1.

23
Time to Detection of HPV 16/18 CIN 2/3 or AIS
Intention to Treat Population
Phase II and III Database for GARDASIL and HPV
16 Vaccine
Merck, unpublished data, Presented at ACIP
meeting, June 2006
v501p5p7p13p15c2w Apr. 28, 2006
24
Anti-HPV 16 GMTs Through 5 Years
Protocol 007
10000
â
GARDASIL

1000
GMT (Log Scale)

100
10
Placebo (Sero () and PCR (-)
to HPV 16 at Day 1)
Vaccination



0


7
12
18
24
30
36
54
60
Time Since Vaccination 1 (Months)
Merck, unpublished data, Presented at ACIP
meeting, June 2006
25
Antibody Titers by Age at Enrollment Anti-HPV 6
GMTs (Quadrivalent HPV vaccine)
Efficacy Program
Immunogenicity Bridge
1600
1500
1300
1100
900
Serum GMT with 95 CI, mMU/mL
700
500
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Age at Enrollment (Years)
Merck, unpublished data, Presented at ACIP
meeting, February 2006
26
Quadrivalent HPV VaccineSummary
  • High efficacy in 16 to 26 year-old females who
    are naïve to the HPV vaccine type
  • HPV 16,18 related CIN 2/3
  • HPV 6,11,16,18 related CIN
  • HPV 6,11,16,18 related external genital lesions
  • No evidence of therapeutic efficacy
  • Efficacy data available through 5 years duration
    of protection and need for booster unknown
  • Safe side effects mainly local reactions

27
  • Vaccine Recommendations

28
Advisory Committee on Immunization Practices
(ACIP)
  • US Federal advisory committee
  • Coordinated and organized by the Centers for
    Disease Control and Prevention (CDC)
  • Provides guidance to Secretary, Health and Human
    Services and Director, CDC on vaccine preventable
    diseases in the US

29
Functions Advisory Committee on Immunization
Practices (ACIP)
  • Develop recommendations and publish written
    guidance for use of vaccines
  • Make recommendations for the Vaccines for
    Children (VFC) Program

30
Vaccines for Children ( VFC) Program
  • Provides vaccine at no cost to eligible children
    lt19 years
  • Medicaid eligible, uninsured, underinsured,
    Native Americans or Alaskan Natives
  • VFC Act passed in 1993
  • Funding for new vaccines occurs through a vote by
    ACIP
  • Federal government establishes contract with
    manufacturer
  • Saves parents and enrolled providers expenses for
    vaccine
  • Provides cost savings to states by purchase of
    vaccine through CDC contracts

31
Childhood Vaccine Doses Distributed by Funding
Source, 2004
Source Biologics Surveillance Data 2004
32
Federal Contract Prices for Vaccines Recommended
Universally for Children and Adolescents 1985
2006
837
155
45
Federal contract price shown for 1985 and 1995
are averages that account for price changes
within that year. Analysis accounts for market
share of specific products. Analysis current as
of May 1, 2006.
33
HPV vaccine
  • ACIP voted to include HPV vaccine in VFC
  • Private sector price 120 per dose
  • VFC contract not yet established

34
Background Information for HPV Vaccine
Recommendations
  • Vaccine and clinical trials
  • HPV epidemiology and HPV related disease
  • Sexual behavior
  • Vaccine acceptability
  • Impact and cost effectiveness
  • Program/implementation issues

35
Provisional ACIP Recommendations
  • Routine vaccination
  • Catch-up vaccination
  • Special situations
  • Precautions and contraindications

36
Routine Vaccination Provisional Recommendation
  • Routine vaccination is recommended for females
    11-12 years of age with three doses of
    quadrivalent HPV vaccine
  • The vaccination series can be started as young as
    9 years of age

37
Rationale Routine Vaccination Females at 11-12
Years
  • Prevalent infection, targeting high risk groups
    not possible
  • Vaccination prior to sexual debut
  • Implementation advantages consistent with young
    adolescent health care visit
  • High antibody titers after vaccination at this
    age
  • Data through 5 years show no evidence of waning
    immunity ongoing studies will monitor duration
    of protection

38
Females 13-26 Years Provisional Recommendation
  • At the beginning of the vaccination program,
    there will be females older than 12 years who
    could benefit from HPV vaccine
  • Vaccination is recommended for females 13-26
    years of age who have not been previously
    vaccinated
  • Ideally vaccine should be administered before
    onset of sexual activity, but females who are
    sexually active should still be vaccinated

39
Rationale Vaccination of Females 13-26 Years
  • Females not yet sexually active can be expected
    to have the full benefit of vaccination
  • Sexually active females may not have full benefit
    because they may have been infected with vaccine
    HPV types, however
  • Only a small percentage are likely to have been
    infected with all four vaccine HPV types
  • For those already infected with gt1 vaccine HPV
    types, vaccine would provide protection against
    disease caused by the other vaccine HPV types
  • Overall vaccine effectiveness would be lower
    most females will still derive some benefit from
    vaccination

40
Special Situations
  • Equivocal or abnormal Pap test
  • Positive HPV test
  • Genital warts
  • Vaccine does not have any therapeutic efficacy
    and will not treat existing infection or disease
  • Vaccine would prevent acquisition of new
    infections

41
Vaccination during Pregnancy Provisional
Recommendation
  • Initiation of the vaccine series should be
    delayed until after completion of pregnancy
  • If a woman is found to be pregnant after
    initiating the vaccination series, remaining
    doses should be delayed until after the pregnancy
     
  • If a vaccine dose has been administered during
    pregnancy, there is no indication for
    intervention
  • Exposures to vaccine in pregnancy should be
    reported
  • (800) 986-8999

42
Precautions and Contraindications
  • Moderate or severe acute illnesses should be
    deferred until after the illness improves
  • History of immediate hypersensitivity or severe
    allergic reaction to yeast or to any vaccine
    component contraindication

43
Cervical Cancer Screening
  • Cervical cancer screening no change
  • 30 of cervical cancers caused by HPV types not
    prevented by the quadrivalent HPV vaccine
  • Vaccinated females could subsequently be infected
    with non-vaccine HPV types
  • Sexually active females could have been infected
    prior to vaccination
  • Providers should educate women about the
    importance of cervical cancer screening

44
Future Data and Issues
  • Further analyses of phase III quadrivalent HPV
    vaccine trials
  • New epidemiologic data on HPV
  • Consideration of vaccine for males
  • Data from bivalent HPV vaccine trials
  • Second generation HPV vaccines
  • Monitoring impact of HPV vaccine

45
  • Thank You

46
Populations in Quadrivalent HPV Vaccine Phase
III Clinical Trials
47
Age-Adjusted Invasive Cancer Incidence Rates,
Among Women, U. S., 2000
United States Cancer Statistics 2000 Incidence
NPCR
Write a Comment
User Comments (0)
About PowerShow.com