Transcript HPV - North Carolina Pediatric Society | Home

Human Papillomavirus Vaccines:
Where Are We Now?
Amina Ahmed, MD
Levine Children’s Hospital
April 5, 2014
Disclosure


I have no relevant financial relationships with the
manufacturers of any commercial products and/or
providers of commercial services discussed in this
CME activity.
I do not intend to discuss an
unapproved/investigative use of a commercial
product/device in my presentation.
Learning Objectives
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
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Characterize the uptake of human papillomavirus (HPV)
vaccines among adolescents in the United States
Identify barriers to the uptake of HPV vaccination and
identify methods for overcoming the barriers
Review the efficacy and safety of HPV vaccines
Review postlicensure effectiveness and safety of HPV
vaccines
Summarize the HCPs role in improving rates of HPV
vaccination
Human Papillomavirus (HPV)



STI with the highest incidence in the United States
 79 million infected
 14 million new infections annually
Primary cause of anogenital warts and cervical cancer
Persistent infection can lead to cervical cancer
 10,000 new cases annually
 4,000 deaths annually
Human Papillomavirus
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
More than 40 types infect mucosal surfaces
 High-risk (oncogenic) and low risk (non-oncogenic)
 16 and 18 most common high-risk types
 Account for 70% of cervical cancer
 6 and 11 most common low-risk types
 Account for 90% of genital warts
Two HPV vaccines currently available
 HPV4 (HPV types 6, 11, 16, 18)
 HPV2 (HPV types 16, 18)
HPV Vaccines
HPV4
HPV2
Manufacturer
Merck & Co (Gardasil)
GSK (Cervarix)
Composition
HPV 6, 11, 16, 18
HPV 16, 18
Schedule
0, 1-2 mo, 6 mo
0, 1-2 mo, 6 mo
FDA Approval
2006- Females 9 through 26 y
2009- Males 9 through 26 y
2009- Females 10 through 25 y
Females: For prevention of vulvar,
vaginal, and cervical cancers and
their premalignant lesions (HPV
16, 18)
Females: For prevention of
cervical cancers and premalignant
conditions
Female and males: For prevention
of genital warts (HPV 6, 11), anal
cancers and premalignant lesions
(HPV 16, 18)
HPV Vaccines: ACIP Recommendations
HPV2
Year
HPV4
ACIP 2006
Routine vaccination of girls at age 11 or 12 y
Vaccination may be administered as early 9 y
Catch-up vaccination for females aged 13-26 y
ACIP 2009
Routine vaccination at age 11 or 12 y
Catch-up vaccination for females aged 13-26 y
ACIP 2009
Provided guidance that HPV4 may be given to
males aged 9-26 y
Where are we now?
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National Immunization Survey-Teen (NIS-Teen)
 HPV vaccination coverage in adolescent girls aged 13-17 y
Coverage increased 2007-2011; no increase in 2012
 2012- 54% received ≥ 1 dose; 33% received all 3 doses
Percentage of girls with at least 1 missed opportunity for
vaccination increased from 21% in 2007 to 84% in 2012
 If missed opportunities eliminated, 93% would have received
≥ 1 dose
MMWR 2013; 62: 591-595
How are we doing?
MMWR 2013; 62: 591-595
Top Five Reasons Parents Choose
Not to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
Adolescent Vaccine Coverage,
2006-2012
MMWR 2012; 61: 671-677
Reasons for Parents Not Vaccinating
Adolescents, NIS-Teen 2008-2010
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Adolescent vaccines (Tdap, MCV4)
1.
Not recommended
2.
Not needed or necessary
3.
Lack of knowledge
4.
Don’t know
HPV vaccines
1.
Not sexually active
2.
Not appropriate for age
3.
Safety concerns
4.
Multiple reasons
Pediatrics 2013; 131: 645-651
Barriers to HPV Vaccination
Parents
Health Care Providers
Not receiving HCP recommendation
Parents’ attitudes and concerns
Need more information
Financial concerns
Child too young to get vaccinated
Knowledge gaps
Safety concerns
Inadequate reimbursement
Cost
Preference for vaccinating older
versus younger adolescents
Preference for vaccinating girls
versus boys
JAMA Pediatr 2014; 168:76-82
Health Disparities in HPV
Vaccine Coverage, 2008-2011
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Evaluated uptake by race/ethnicity, poverty, and combination of
race/ethnicity and poverty
 HPV vaccine initiation increased by 16%
 MCV4 26%, Tdap 37%
Initiation highest for Hispanic> black > white
 For every race/ethnicity, coverage higher for below-poverty
Completion higher for below-poverty in non-Hispanic black, nonHispanic other and Hispanic groups versus above poverty
 Below poverty Hispanics had highest completion (45%)
Clin Infect Dis 2014; 58: 238-41
Clin Infect Dis 2014; 58: 238-41
Improving HPV Vaccination Coverage
1.
2.
3.
Education of parents
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Updated educational materials at
www.cdc.gov/vaccines/who/teens/index.html
HCPs must increase the consistency and strength of
HPV vaccination recommendations

Tip sheet at www.cdc.gov/vaccines/sho/tens/forhcp-tipsheet-hpv.html
Reduction of missed opportunities

Access to healthcare is not an issue
MMWR 2013; 62: 591-595
Top Five Reasons Parents Choose
Not to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
Human Papillomavirus
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Most common STI in the US
 79 million currently infected
 14 million new infections per year
HPV can cause cancers of the cervix, vagina, vulva,
penis, anus, and mouth or throat
 26,000 cases per year (8,800 among males)
 10,000 cases of cervical cancer
 4,000 deaths annually
HPV Virology
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DNA virus in family Papillomaviridae
Encodes for 6 early (E) proteins and 2 late (L) proteins
 Purified L1 protein self-assembles to form empty
shells that resemble a virus-like particles (VLPs)
> 100 types split into “high-risk” and “low-risk” based
on association with the development of cervical cancers
High- risk (6, 18, 31, 45)
-Cancer precursors
-Anogenital cancers
Mucosal
( 40 types)
Low-risk (6, 11, others)
-Genital warts
More than 100
HPV types
-Low grade cervical abnormalities
-Recurrent respiratory papillomatosis
Cutaneous
( 60 types)
Cutaneous warts
HPV Epidemiology
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Worldwide point prevalence is 10%
US - 79 million females and males infected
 74% infections occur among those 15-24 y of age
 Prevalence of all types is 66% in males
75-80% of sexually active adults will acquire HPV
genital tract infection by age 50 y
 Prevalence 33% in 14-19 y
 College students- 26% at entry, 43% acquired
Prevalence of HPV among Females
in the United States
JAMA 2007; 297; 813-819
Prevalence of HPV among Females
in the United States
Am J Obstet Gynecol 2013; 169-175
HPV Prevalence in Men
of Various Populations
J Infect Dis 2006; 194: 1044-1057
HPV Detection in Men
by Anogenital Site or Specimen
J Infect Dis 2006; 194: 1044-1057
Transmission of HPV
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Almost exclusively acquired from sexual exposure
 Genital-genital, oral-genital, anal-genital or
oral-anal contact
 Most transmission is asymptomatic
Nonsexual transmission uncommon
 Mother to newborn baby
 ? Fomite
Natural History of HPV Infection
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Majority of infections are transient and asymptomatic
 70% clear within 1 year
 90% clear within 2 years
Persistent infection with high-risk types of HPV is the
most important risk factor for cervical cancer
 Time from infection to cancer is usually decades
 Makes it difficult to understand impact of vaccine
Disease and Estimated Percentage of Cases
Associated with HPV Infection
Disease
Affected
sex
Estimated number of
cases (2003)
Percentage of
cases
attributable to
oncogenic HPV
Anogenital warts
M, F
100
Recurrent respiratory
papillomatosis
M, F
100
F
100
CIN 1, 2, 3
Cancer
F
12,000
100
M, F
4,200
90
Vulvar, vaginal
F
4,500
40
Penile cancer
M
1,000
40
M, F
29,000
12
Cervical cancer
Anal cancer
Head and neck cancers
Clin Infect Dis 2006; 43: 624-629; MMWR 2007; 56:1-23
Top Five Reasons Parents Choose
Not to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
HPV Vaccines
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Recombinant capsid proteins (L1) self assemble into VLPs
 Mimic virus but do not contain viral DNA
Both vaccines highly efficacious against HPV 16 and 18related cervical precancer lesions
HPV4 highly efficacious against HPV 6 and 11-related
genital warts and HPV 16 and 18-related vaginal and
vulvar precancer lesions
Efficacy of HPV2 and HPV4 in Females
MMWR 2010; 59: 626-629
Efficacy of HPV4 in Males
MMWR 2010; 59: 630-632
Longevity of Immunogenicity
Lancet 2006; 367: 1247-1255
Postlicensure Effectiveness
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United States
 56% reduction in prevalence of HPV strains 6, 11, 16 and 18
in adolescent girls
 Only 33% girls received 3 doses
 36% reduction in genital warts in US girls 15-19 y despite low
HPV immunization rates
Australia
 77% reduction in prevalence of HPV 6, 11, 16 and 18 in
adolescent girls within 3 years of vaccine introduction
 3 dose immunization of 70%
Denmark
 45% reduction in genital warts in girls 16-17 y
http://aapnews.aappublications.org/content/35/3/9.1
Decreased Prevalence of HPV
Infection, United States (NHANES)
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Prevalence data compared for prevaccine era (20022006) and vaccine era (2007-2010)
 In 2010 3-dose coverage 33%
Sampled females 14-19 y of age
 4,000 per period
 Vaccine type HPV declined from 12% to 5%
Despite low uptake, vaccine effectiveness for 1 dose
was high (82%)
J Infect Dis 2013; 208: 385-393
Prevalence of HPV Types among Females 14-19
years, 2003-2006 and 2007-2010 (NHANES)
J Infect Dis 2013; 208: 385-393
Fall in HPV Prevalence Following a
National Vaccination Program
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HPV prevalence in Australian women 18-24 y from
2005-2007 (prevaccine) compared with 2010-2011
(postvaccine)
Prevalence of HPV types 6, 11, 16, 18 significantly
lower postvaccine compared with prevaccine
Vaccinated women consistently had lowest rates of
HPV infection
 Vaccine effectiveness 73%
J Infect Dis 2012; 206: 1645-1651
J Infect Dis 2012; 206: 1645-1651
Decreased Risk of Genital Warts
after HPV Vaccination: Denmark
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Linkage of nationwide, individual information on HPV4
vaccination with subsequent risk of GW
Birth cohorts 1989-1999
 248,403 vaccinated versus 151,367 unvaccinated
 Coverage rate 14% (birth 1989-90) to 90% (birth
1995-96)
RR of GWs among girls who received at least 1 dose of
vaccine compared with unvaccinated girls ranged from
0.12 (1995-96) to 0.62 (1989-90)
Clin Infect Dis 2013; 57: 929-934
Risk of Genital Warts Among Girls Vaccinated Against
HPV Types 6, 11, 16, and 18 (≥ 1 dose) vs
Unvaccinated Girls, by Birth Cohort, 2006-2012
Clin Infect Dis 2013; 57: 929-934
Top Five Reasons Parents Choose Not
to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
HPV4 Safety and Adverse Events
N Engl J Med 2007; 356: 1915-1927
HPV2 Safety and Adverse Events
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Pooled analysis of 23,713 females aged 10-25
Larger proportion of persons reported one injectionsite symptom in HPV2 group compared with controls
 92% reported pain, 48% redness, 44% swelling
compared with 64-87%, 24-28%, and 17-21% in
the control groups
Proportion of persons reporting an SAE similar in
vaccine and control groups (5.3% vs 5.9%)
Incidence of potential AI disorders did not differ
MMWR 2010; 59: 626-629
Postlicensure Safety of HPV Vaccines
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2006-2013: 56 million doses HPV4 distributed in US
VAERS received 21,194 AE reports for females
 92% nonserious
 Syncope, dizziness, nausea, HA, fever and urticaria
 Injection site pain, redness, swelling
 8% serious
 HA, nausea, vomiting, fatigue, dizziness, syncope,
generalized weakness
Reporting consistent with prelicensure clinical trial data and
reporting patterns remained consistent with 2007 summary
MMWR 2013; 62: 591-595
Postlicensure Safety of HPV Vaccines
MMWR 2013; 62: 591-595
Postlicensure Safety of HPV Vaccines
MMWR 2013; 62: 591-595
Top Five Reasons Parents Choose Not
to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
Risk Factors
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Young age (< 25 y)
 Prevalence highest among women 20-24 y of age
Race
 Highest prevalence in non-Hispanic blacks (59%)
 Lowest in non-Hispanic whites (39%)
Sexual history
 Number of recent and lifetime partners
 Partners’ sexual history
Coinfection with other STIs
 HIV associated with incidence, persistence and progression
Epidemiology of Sexual Behavior
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National Survey of Family Growth
 24% of females sexually active by age 15 y
 40% by age 16 y and 70% by age 18 y
Youth Behavioral Risk Survey, 2005
 4% of female students sexually active by age 13 y
th graders and 20% of 12th graders had 4
 6% of 9
or more partners
Epidemiology of Sexual Behavior
J Infect Dis 2008; 197: 279-282
Top Five Reasons Parents Choose Not
to Vaccinate Against HPV
1.
Vaccine not needed (19%)
2.
Vaccine not recommended (14%)
3.
Vaccine safety concerns (13%)
4.
Lack of knowledge about vaccine or disease (13%)
5.
Daughter is not sexually active (10%)
MMWR 2013; 62: 591-595
Recommending HPV Vaccines
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Strong recommendation from HCP is the single best
predictor of vaccination
 HPV causes cancers of the cervix, vagina, vulva
and penis
 HPV vaccine has been shown to be very effective
in preventing cancers and precancers
 Vaccination is important before the start of any
sexual activity
Scheduling future vaccines with reminders will reduce
missed opportunities
Summary:
Improving HPV Vaccination Coverage
1.
2.
3.
Education of parents

Updated educational materials at
www.cdc.gov/vaccines/who/teens/index.html
HCPs must increase the consistency and strength of
HPV vaccination recommendations

Tip sheet at www.cdc.gov/vaccines/sho/tens/forhcp-tipsheet-hpv.html
Reduction of missed opportunities

Access to healthcare is not an issue
MMWR 2013; 62: 591-595