Safety and Immunogenicity of Human Papillomavirus (HPV) Vaccine in Solid Organ Transplant Recipients
Condition: Transplant
Study type: Interventional
Phase: Phase 3

Summary: 
      Human papillomavirus (HPV) affects a significant number of transplant patients. In women,
      human papillomavirus (HPV) causes genital warts, pre-cancerous areas of the cervix, and
      cervical cancer. In men, the virus can cause warts of the anal and genital areas. Men can
      also sexually transmit the virus to their partners. A patient who has had an organ transplant
      is at higher risk of infections as well as cancers because of the lifelong immune suppressive
      medications. HPV vaccination is effective in the prevention of cervical cancer and is now
      recommended for all females aged 9-26 years by Alberta Health and Wellness and the Canadian
      National Advisory Committee on Immunization (NACI). However, how well the vaccine works in
      transplant patients is not known.

      This study is being done to look at response of the immune system to HPV vaccine in men and
      women up to the age of 35 who have had an organ transplant. Men are also included in this
      study because they have the potential to get anal / genital warts and transmit the virus to
      their partners. The total duration of the study is three years. Fifty female and male solid
      organ transplant recipients (lung, heart, liver, kidney, pancreas, small bowel or combined
      organ transplants) on immunosuppression will be enrolled in the study.
    

Detailed description: 
      Cervical cancer affects a significant proportion of the female population. In Canada, it is
      estimated that there will be 1,350 new diagnoses of cervical cancer in 2007 and 390 deaths
      [1]. Human papillomavirus (HPV) is the causative agent in genital warts, cervical
      intraepithelial neoplasia, and cervical cancer. In this study, the vaccine will also be given
      to males, because males can develop anogenital warts and can transmit the virus to their
      partners. HPV is a nonenveloped DNA virus containing early and late genes. Although
      approximately 40 HPV types can infect the genital tract, only a few cause the majority of
      disease. For example, cancer-causing HPV includes HPV 16 whereas benign tumours are caused by
      HPV 6 [2].

      HPV vaccine is a quadrivalent vaccine consisting of HPV types 6,11,16,18. Types 16 and 18 are
      implicated in the majority (~70%) of cervical cancers and at least half of CIN 2 and 3
      lesions. Types 6 and 11 cause 90% of genital warts. The vaccine contains virus-like particles
      (VLPs) of the L1 proteins of the four serotypes and is adjuvanted with aluminum
      hydroxyphosphate sulphate. The vaccine does not contain live virions and cannot cause HPV
      disease. It is administered by intramuscular injection in three doses at 0, 2 months, and 6
      months [2].

      HPV vaccination is effective in the prevention of high grade cervical lesions and is now
      recommended for all females aged 9-26 years by the Canadian National Advisory Committee on
      Immunization (NACI) [3]. Although the vaccine is licensed for females, males can also develop
      anogenital warts and can transmit the virus to their partners. Immunogenicity trials have
      shown similar response to vaccine in adolescent males compared to females [15]. In addition,
      if women have been infected with 1-3 out of the four serotypes, vaccination appears to
      prevent cervical lesions from the remaining serotypes [16]. Therefore, although the vaccine
      is licensed for women ≤ 26 years old, it may also be applicable to somewhat older women who
      may not have acquired all four serotypes.

      Solid organ transplantation is a life-saving modality; however, patients are on life-long
      immunosuppression which puts them at increased risk of infections as well as cancers. Studies
      have shown a high incidence of HPV infection in transplant recipients ranging from 17.5-45%
      [4-8]. An evaluation of 105 renal transplant recipients showed that 17.5% patients were
      infected with HPV [5]. Another study of 39 renal transplant recipients screened for HPV
      showed the presence of HPV in 30.7% of patients, primarily in the cervix [6]. Therefore, the
      risk of HPV infection has been estimated to be 17 times greater in renal transplant
      recipients than a matched immunocompetent population. Ano-genital neoplasia, related to HPV,
      is about 16-20 times more common in transplant recipients [5,6].

      Yearly physical examinations of the anogenital area and annual Pap smears are recommended for
      transplant recipients [9]. However, there are no data on the immunogenicity of quadrivalent
      HPV vaccine in solid organ transplant recipients and no formal recommendations for
      vaccination in transplant recipients exist. Given that this is a patient population that is
      uniquely susceptible to HPV infection and its sequelae, it is important that vaccine
      immunogenicity be studied in transplant recipients.
    

Intervention name(s): Human papillomavirus quadrivalent vaccine
Intervention type(s): Biological
Intervention description(s): Patients meeting the inclusion / exclusion criteria will be enrolled from outpatient transplant clinics. Upon enrolment, baseline serum will be obtained and patients will be given the first dose of vaccine. Two months later, serum will again be obtained and the second dose of vaccine will be administered. Finally, at month 6, serum will be obtained and the third dose of vaccine will be given. The final serum samples will be collected at months 7, 12 and 36. At 48 hours and 7 days after each vaccination, patients will be contacted by telephone for local and systemic adverse effect reporting.
Other intervention name(s): Gardasil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Lung transplant; Liver transplant; Kidney transplant; Pancreas transplant; HPV; Human Papillomavirus Quadrivalent Vaccine