Immunogenicity of Off-Schedule Dosing of HPV Vaccine
Condition: Papilloma Viral Infection
MeSH terms: Virus Diseases; Papillomavirus Infections; Papilloma
Study type: Observational

Summary: 
      The purpose of this study is to gain a better understanding of the body's response to a human
      papillomavirus (HPV) (sexually transmitted disease), vaccine and booster shot. The study will
      also determine factors related to adolescents not following vaccination schedules. The HPV
      vaccine requires 3 doses (shots). Girls sometimes receive the 3 shots at the recommended time
      and sometimes girls receive the shots at non-recommended times. This study will evaluate if
      getting the shots at non-recommended times affects the level of protection provided by the
      vaccine. Participants will include about 1400 girls 9-17 years old receiving a third dose of
      HPV vaccine from their primary care clinician. The parent/legal guardian of each subject may
      answer a questionnaire related to the vaccine schedule. Study procedures include: medical
      history, questionnaires and blood draws. Participants will be involved in the study for about
      6 months from time of enrollment.
    

Detailed description: 
      The immune response to the quadrivalent human papillomavirus (HPV) vaccine in the
      non-clinical trial settings is unknown. In addition, the immune response following
      administration of vaccine at substantially prolonged intervals is unknown. Early indications
      suggest that many girls will be receiving the vaccine at prolonged intervals and that this
      timing may affect immunogenicity. The lack of knowledge about the immunogenicity of prolonged
      intervals between vaccine doses precludes evidence based recommendations for patients who are
      substantially late for their second or third dose. Some clinicians currently restart the
      series while others give the doses at the incorrect interval (unpublished observation)
      without the ability to counsel their patients as to their expected level of immune response
      or protection. Examining the immune response prior to the third dose and at one and six
      months after the third dose will allow a better understanding of the immunogenicity of this
      vaccine and immune response to booster doses. Furthermore, determining factors related to
      non-adherence in the adolescent age group is important and timely. As an increasing number of
      vaccines are being recommended to the adolescent age group, elucidating factors involved with
      non-adherence to the recommended dosing schedule is now critical. This information can guide
      interventions that aim to increase adolescent adherence to the recommended schedules.
      Eligible girls 9 - 17 years old receiving the quadrivalent HPV vaccine from their primary
      care provider will be enrolled into this study on the day of, but prior to, receiving their
      third HPV vaccine dose or at approximately 28 days after the third HPV dose . Blood for
      immunogenicity testing will be obtained up to three times throughout the study: one month
      (Study Day 28) and six months (Study Day 180) after the third dose (Study Day 0) for all
      subjects and just prior to the third dose for subjects on time for their third dose
      (regardless of the time interval between the first and second dose). The primary analysis
      will be based on comparing the geometric mean titer (GMTs) and sero-response rate of subjects
      receiving the vaccine doses at substantially prolonged intervals to GMTs and sero-response
      rate of subjects receiving the second and third dose on time. In addition, on Study Day 0,
      patient and parent related factors known to impact health care utilization may be measured
      using a questionnaire given to parents/legal guardians and 14 to 17 year old subjects.
      Analysis based on a health care utilization model will be used to determine factors
      associated with non-adherence to the vaccine schedule. Initially, all subjects meeting
      eligibility criteria will be enrolled regardless of timing of the second and third vaccine
      doses. When a study arm reaches the accrual target, it will be closed to enrollment.
      Enrollment for the entire study will remain open until the control and three primary
      experimental arms have completed enrollment One or more experimental arms may be dropped from
      the study after monitoring of accrual rates indicates that it/they cannot be fully enrolled
      in a timely fashion. Monitoring will occur monthly. Assessment of accrual rates will occur
      semi-annually. The primary objective is to compare the GMT one month after completing the
      three dose vaccination series in 9 to 17 year old subjects who received the second and/or
      third dose at substantially prolonged intervals to subjects who receive both the second and
      third dose on time after adjusting for age.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Girls 9-17 years old receiving third dose of HPV vaccine from primary care clinician.
        Parent/legal guardian will participate by answering a questionnaire to determine factors
        related to non-adherence to recommended vaccine schedule.
      
Biospecimen description: 
      Serum samples.
    
Keywords: adolescent; children; HPV; human papillomavirus; vaccine; women