The Development of a Human Papillomavirus Vaccine

							  Human Papillomavirus
 (HPV) and HPV Vaccine

 Epidemiology and Prevention of Vaccine-
          Preventable Diseases

  National Center for Immunization and
           Respiratory Diseases
Centers for Disease Control and Prevention
              Revised March 2008
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   Human Papillomavirus (HPV)

• Small DNA virus
• More than 100 types identified based
  on the genetic sequence of the outer
  capsid protein L1
• 40 types infect the mucosal
  epithelium




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        Human Papillomavirus Types
          and Disease Association
    mucosal/genital                    nonmucosal/cutaneous
     (~40 types)                           (~60 types)

high-risk types
  16, 18, 31, 45      low-risk types           skin
  (and others)             6, 11
                        (and others)          warts
                                             (hands
                                            and feet)

•low grade cervical   •low grade cervical
  abnormalities        abnormalities
•cancer precursors    •genital warts
•anogenital cancers   •laryngeal papillomas
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        HPV-Associated Disease

Type         Women                      Men
16/18 70% of Cervical Cancer   70% of Anal Cancer
      70% of Anal/genital      Transmission to women
      Cancer
 6/11 90% of Genital Warts     90% of Genital Warts
      90% of RRP lesions       90% of RRP lesions
                               Transmission to women




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   Natural History of HPV Infection

     Within 1 Year           1-5 Years         Up to Decades


                   Persistent            CIN          Cervical
                    Infection            2/3          Cancer
  Initial
   HPV
Infection
                     CIN 1




            Cleared HPV Infection
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         HPV Clinical Features

• Most HPV infections are asymptomatic
  and result in no clinical disease
• Clinical manifestations of HPV infection
  include:
   – anogenital warts
   – recurrent respiratory papillomatosis
   – cervical cancer precursors (cervical
     intraepithelial neoplasia
   – Cancer (cervical, anal, vaginal, vulvar,
     penile, and some head and neck cancer)

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         HPV Epidemiology

• Reservoir         Human

• Transmission      Direct contact,
                    usually sexual
• Temporal          None
  pattern

• Communicability   Presumed to be
                    high

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HPV Disease Burden in the United States

• Anogenital HPV is the most common
  sexually transmitted infection in the US
   – Estimated 20 million currently infected
   – 6.2 million new infections/year
• Common among adolescents and young
  adults
• Estimated 80% of sexually active women
  will have been infected by age 50
• Infection also common in men

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Cervical Cancer Disease Burden in
         the United States
• The American Cancer Society
  estimates that in 2006
  –9,700 new cervical cancer cases
  –3,700 cervical cancer deaths
• Almost 100% of these cervical cancer
  cases will be caused by one of the 40
  HPV types that infect the mucosa



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     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
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 Human Papillomavirus Vaccine
• HPV L1 major capsid protein of the
  virus is antigen used for
  immunization
• L1 protein expressed in yeast cells
  using recombinant technology
• L1 proteins self-assemble into virus-
  like particles (VLP)
• VLPs are noninfectious and
  nononcogenic

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                HPV Vaccine Efficacy*
           Endpoint                                        Efficacy
           HPV 16/18-related                                 100
           CIN2/3 or AIS

           HPV 6/11/16/18                                       95
           related CIN

           HPV 6/11/16/18                                       99
           related genital warts
*Among 16-26 year old females. CIN – cervical intraepithelial neoplasia; AIS –
adenocarcinoma in situ                                                           12
        HPV Vaccine Efficacy

• High efficacy among females without
  evidence of infection with vaccine
  HPV types
• No evidence of efficacy against
  disease caused by vaccine types or
  which participants were infected at
  the time of vaccination
• Prior infection with one HPV type did
  not diminish efficacy of the vaccine
  against other vaccine HPV types
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      Routine HPV Vaccination
        Recommendations
• ACIP recommends routine vaccination
  of females 11-12 years of age
• The vaccination series can be started
  as young as 9 years of age at the
  clinician’s discretion
• “Catch-up” vaccination recommended
  for females 13 through 26 years of age



   MMWR 2007;56(RR-2):1-24
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     HPV Vaccination Schedule
• Routine schedule is 0, 2, 6 months
• Minimum intervals
  –4 weeks between doses 1 and 2
  –12 weeks between doses 2 and 3
  –24 weeks between doses 1 and 3
• Do not restart the series if the
  schedule is interrupted
• Administer at same visit as other age-
  appropriate vaccines (e.g., Tdap, MCV)
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  Human Papillomavirus Vaccine

• HPV vaccine is not currently licensed
  for use among males
   –Clinical efficacy data are not
    available
   –Off-label use not recommended
• Efficacy studies in males are in
  progress


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          HPV Vaccine
        Special Situations*
•   Equivocal or abnormal Pap test
•   Positive HPV DNA test
•   Genital warts
•   Immunosuppression
•   Breastfeeding



*Vaccine can be administered

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           HPV Vaccine
         Adverse Reactions
• Local reactions       84%
  (pain, swelling)
• Fever                 10%*
• No serious adverse reactions
  reported



*similar to reports in placebo recipients (9%)

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  Syncope Following Vaccination

• An increase in the number of reports of
  syncope has been detected by the
  Vaccine Adverse Event Reporting System
  (VAERS)
• 11-18 year old females have contributed
  most of the increase
• Serious injuries have resulted
• Providers should strongly consider
  observing patients for 15 minutes after
  they are vaccinated

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          HPV Vaccine
Contraindications and Precautions
• Contraindication
  –Severe allergic reaction to a
    vaccine component or following a
    prior dose
• Precaution
  –Moderate or severe acute illnesses
    (defer until symptoms improve)



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  HPV Vaccination During Pregnancy

• 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
• Women vaccinated during pregnancy
  should be reported to the Merck registry
  (800.986.8999)
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  MMWR 2007;56(RR-2):1-24
          HPV Vaccine
      Storage and Handling

• Store at 36°F-46°F (2°C-8°C)
• Protect from light
• Do not expose to freezing
  temperature
• Remove from refrigeration
  immediately before administration




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 CDC Vaccines and Immunization
      Contact Information


• Telephone   800.CDC.INFO

• Email       nipinfo@cdc.gov

• Website     www.cdc.gov/vaccines


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