HPV Vaccine Effectiveness in Partially Vaccinated Girls in Uganda
HPV Vaccine Effectiveness in Partially Vaccinated Girls in Uganda
Background:

 - Cervical cancer is one of the leading causes of cancer death in women worldwide and in
 Uganda. It is caused by the human papillomavirus (HPV). A vaccine against HPV was offered for
 all 10-year-old girls in the Nakasongola district of Uganda from October 1, 2008, to October
 31, 2009. The HPV vaccine requires three doses; however, some girls received only one or two
 doses. Researchers want to compare vaccine immunogenicity in girls who received all three
 doses with those who had only one or two doses.

 Objectives:

 - To examine the immunogenicity (antibody levels) of girls in Uganda who received only one,
 two or three doses of HPV vaccine.

 Eligibility:

 -  Girls who will be at least 12 years old by October 31, 2011, and had at least one dose
 of the HPV vaccine.

 -  All participants will come from the Nakasongola district of Uganda.

 Design:

 -  Participants will have a physical exam and answer questions about their medical history
 and HPV risk.

 -  Participants will provide a single blood sample for testing.

 -  Treatment and vaccines will not be provided as part of this study. Girls who did not
 receive all three doses of the HPV vaccine will be given information about the nearest
 health center. Health centers will provide the missed doses free of charge.
Background:

 Recent experience with HPV vaccine implementation in low resource settings has suggested that
 high vaccine coverage for all three doses could be achieved provided programs are planned
 well and have full and complementary components in place. However, some locations experienced
 substantial rates of partially vaccinated girls, those who received only one or two doses.
 From the vaccine trial data published thus far, we know that the vaccines produce high levels
 of type-specific anti-HPV antibodies which begin to stabilize past 24 months
 post-vaccination. Without an immune correlate of protection, it is difficult to know whether
 girls who received one or two vaccine doses will still experience the same benefit of
 protection from HPV infection as those who received all three doses of vaccine.

 Recent data from a trial of a two-dose regimen of vaccination of girls aged 9-13 years in
 Vancouver, Canada have suggested that the immune response of girls who received only two
 doses was non-inferior both to that of girls who received 3 doses and to that of adult women
 aged 16-25 years who also received 3 doses. In a complementary study in Guanacaste, Costa
 Rica, vaccine efficacy (defined as 12-month vaccine type-specific infection persistence)
 among adult women who received either one or two doses of HPV vaccine as a part of the Phase
 IIb clinical trials of Cervarix (GSK) was similar to women who received all three vaccines
 doses.

 This proposed study would provide additional insight into the immunogenicity of HPV vaccine
 among partially vaccinated girls in Uganda, which could add supportive evidence in an African
 adolescent population (currently not represented in any clinical studies of HPV vaccines) of
 the immunological implications of receiving less than 3 doses of HPV vaccine.

 Objective:

 To investigate whether the anti-HPV 16 and/or anti-HPV-18 immune responses elicited by the
 bivalent vaccine for girls who received one dose and those who received two doses are similar
 at greater than or equal to 24 months (after last dose) to girls who received all three doses
 of bivalent HPV vaccine.

 Eligibility:

 Girls who received at least one dose of the HPV vaccine, 12-20 years of old, in apparent good
 general health.

 Design:

 This is a cross-sectional immunogenicity study with three groups:

 Group 1 - 200 girls who received only one dose of HPV vaccine as a part of the PATH-UNEPI HPV
 vaccine demonstration project;

 Group 2 - 200 girls who received only two doses of HPV vaccine as a part of the PATH-UNEPI

 HPV vaccine demonstration project; and

 Group 3 - 200 girls who received all three doses of HPV vaccine as a part of the PATH-UNEPI
 HPV vaccine demonstration project.

 This study will enroll girls (by group) within one district of Uganda from an HPV vaccine
 registry maintained by the district.

 Antibody level will be parameterized as the geometric mean titre of serum antibody to HPV
 types 16 and/or 18 at greater than or equal to 24 months after last dose of vaccine. Titres
 will be measured using the polyclonal Direct VLP ELISA.
-  INCLUSION CRITERIA:

 The following inclusion criteria will be reviewed at the time of enrollment, and where
 noted, confirmed at the clinic visit, immediately prior to blood draw:

 -  Subject is aged 12-17 years as of August 31, 2011.

 -  Subject received at least one dose of HPV vaccine, Cervarix (GSK, UK), from October 1,
 2008 through October 31, 2009 as a part of the PATH HPV vaccine demonstration project
 in Nakasongola, Uganda.

 -  Signed and dated informed written consent form (with both parent and subject s
 signatures) received (confirmed at clinic visit).

 -  Subject is afebrile, in good apparent health (confirmed at clinic visit).

 -  Subject assents to participate (confirmed at clinic visit).

 -  Subject is able to comply with the study protocol (confirmed at clinic visit).

 -  Subject plans to stay in Nakasongola for the duration of enrolment, which is expected
 to be about week between signed consent and blood draw.

 EXCLUSION CRITERIA:

 The following exclusion criteria will be reviewed at the time of enrollment, and where
 noted, confirmed at the clinic visit.

 -  Prior HPV vaccination outside the PATH HPV vaccine demonstration project period.

 -  Subject is known to be pregnant or lactating at the time of the scheduled blood draw
 (confirmed at clinic visit).

 -  Subject has an apparent moderate or severe acute illness or has fever (confirmed at
 clinic visit).

 -  Clinical history of bleeding disorders such as haemophilia, thrombocytopenia, or
 anticoagulant therapy.

 -  Investigational drug or investigational vaccine or licensed vaccine administered
 during the period from 30 days before the date of the scheduled blood draw (confirmed
 at clinic visit).

 -  Subject receives immunoglobulins and/or any blood products during the period from 30
 days before the date of the scheduled blood draw (confirmed at clinic visit).

 -  Subject or subject s parents refused to sign written consent.

 -  Subject does not assent at the time of the blood draw.