Multicenter Trial Evaluating the Immunogenicity of HPV Vaccination in Girls on Immunosuppressive Therapy.
Multicenter Trial Evaluating the Immunogenicity of HPV Vaccination in Girls on Immunosuppressive Therapy.
PRIMAVERA is a Phase IIa clinical trial, with the objective to assess the immunologic
 response to HPV vaccine in a population of immunocompromised girls. The principal hypothesis
 is that the immunologic response to tetravalent vaccine in girls who received
 immunosuppressive treatment is comparable to the immunologic response in girls that are not
 immunosuppressed.
The human papillomaviruses (HPV) are the cause of the most common sexually transmitted
 infection. Among oncogenic HPV, HPV 16 and 18 are found in 70% of invasive cancers. Among the
 non-oncogenic HPV, HPV 6 and 11 are found in 90% of anogenital warts. Two prophylactic
 vaccines are currently available: Gardasil ® protects against HPV 6, 11, 16 and 18 and
 Cervarix ® that protects against HPV16 and 18. Gardasil ® is indicated for the prevention of
 high-grade cervical dysplasia (CIN2-3), cancers of the cervix, high-grade dysplasia of the
 vulva (VIN2-3) and genital warts.

 The choice of Gardasil ® is linked to the theoretical risk of graft rejection with the
 bivalent vaccine, and the fact that the frequency of anogenital warts related to HPV 6 and 11
 is increased in the immunocompromised population.

 The immunosuppressed women are more likely to present abnormal cervical smears than general
 population.

 A notice on the age of vaccination against HPV for girls to receive a transplant was made by
 the High Council of Public Health, recommending that vaccination against HPV could be offered
 to girls to benefit a transplant before the age of 14 years and according to data from the
 MA. The High Council of Public Health also renewed its request that studies be conducted
 specifically on the vaccination of girls and young women, immunocompromised, including those
 receiving immunosuppressive therapy.

 The primary objective is to evaluate the persistence of immunological response to tetravalent
 HPV vaccine at 18 months after first dose of vaccine.
Inclusion Criteria:

 -  Female gender

 -  Age ≥ 9 years and < 18 years

 -  Weight ≥ 25 kg

 -  Solid organ transplantation: kidney, liver, heart, lung, intestinal or combined
 transplant; or systemic lupus erythematosus or other systemic immune disease

 -  Transplantation or diagnosis of lupus or diagnosis of systemic immune disease since
 more than 6 months

 -  Immunosuppressant treatment by anti-metabolites or calcineurin inhibitors, with or
 without associated corticosteroids

 -  Minimum required period of 3 months considered as stable after transplantation or
 without relapse of lupus according to physician evaluation

 -  In case of sexual activity (assessed by auto-declaration): onset less than one year
 before inclusion

 -  Written informed consent signed by the investigator and the legal representatives of
 the patient, and assent by the patient

 Exclusion Criteria:

 -  Male gender

 -  Pregnancy

 -  Age < 9 years or ≥ 18 years

 -  Previous HPV vaccination

 -  Immunosuppressive treatment by anti-TNF (adalimumab, etanercept, infliximab) or
 monoclonal antibodies (rituximab, anakinra, abatacept) during the last 3 months

 -  Active malignancy

 -  Active opportunistic infection

 -  HIV infection

 -  Concurrent clinical trial