The Organ Transplant Recipient HPV and Skin Cancer Study

Study Overview
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Brief Summary
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Solid organ transplant recipients (OTRs) receive lifelong immunosuppressive therapy, which puts them at increased risk of cutaneous and mucosal cancers. In particular, OTRs have increased risk of skin cancer and cancers caused by human papillomavirus (HPV), including cervical cancer and oropharyngeal cancer. There is currently limited knowledge on risk factors for HPV infection and skin cancer in OTRs, and limited knowledge on the natural history of HPV infection and cervical neoplasia in OTRs compared with immunocompetent controls. With a continuously increasing number of OTRs, there is a growing need to improve our understanding of the long-term reactions to immunosuppression. The overall aim of this study is to investigate long term effects of immunosuppression on cutaneous and mucosal epithelium in Danish OTRs, including the risk of skin dysplasia and skin cancer, cervical and oral HPV infection and HPV-related dysplasia and cancer in OTRs. This study will be designed as a prospective observational cohort study based on clinical data and data from nationwide Danish registries. A total of 600 female OTRs, 600 male OTRs and 600 female controls will be included from Danish dermatology departments. The study aims to provide knowledge relevant for improving prevention of skin- and HPV-related cancers in OTRs, including personalized screening recommendations according to individual patient risk.

Detailed Description
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AIMS The specific research objectives of this study are: To investigate the overall and type-specific prevalence, incidence and persistence of cervical HPV infection in OTRs compared to immunocompetent controls. To investigate the overall and type-specific prevalence of oral HPV infection in female OTRs compared to immunocompetent controls. To determine the role of lifestyle and clinical factors for the occurrence of cervical and oral HPV infection in female OTRs. To investigate the prevalence and incidence of HPV-related dysplasia and cancer in female OTRs compared with immunocompetent controls. To determine the role of lifestyle, clinical and organ transplantation-related factors for the prevalence and incidence of skin dysplasia in OTRs. To investigate associations between skin dysplasia and prevalence of cervical HPV infection and VZV infection in OTRs. METHODS The study will be designed as a clinical prospective cohort study. A total of 600 female OTRs, 600 male OTRs and 600 female immunocompetent controls will be included from the Departments of Dermatology at Bispebjerg, Gentofte and Roskilde Hospitals, Denmark. The following data will be collected from OTRs: At baseline: Questionnaire, dermatologic skin assessment, assessment of skin photodamage (only OTRs recruited from Bispebjerg Hospital), medical record information, cervico-vaginal HPV self-sample test (women only), oral sample for HPV test (women only), blood sample for future research, blood sample for vitamin D test (only OTRs recruited from Bispebjerg Hospital). After 6 months: New blood sample for vitamin D test (only OTRs recruited from Bispebjerg Hospital). After 12 months: New cervico-vaginal HPV self-sample test (women only). The following data will be collected from female immunocompetent controls: At baseline: Questionnaire, cervico-vaginal HPV self-sample test, oral sample for HPV test. After 12 months: New cervico-vaginal HPV self-sample test. A REDCap database will be established for study data. The RedCap database is encrypted and accessed electronically with personal user-ID and password. The study population will be linked with nationwide Danish registries and clinical databases. From these registers information on cases of precancerous lesions and cancer; other HPV-related conditions; participation in HPV vaccination and cervical cancer screening; co-morbidities, pregnancies, births and medicine use; socio-demographic characteristics; and emigration and death of women in the study population will be obtained. Registry linkage will be performed for up to 15 years after end of study.

Official Title
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The Organ Transplant Recipient HPV and Skin Cancer Study

Conditions
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Solid Organ Transplant Recipient, Skin Cancer, Skin Dysplasia, HPV Infection, Cervical Intraepithelial Neoplasia, Cervical Cancer, HPV-Related Malignancy

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for OTRs: Patients aged ≥18 years Solid organ transplantation recipients, i.e. kidney-, liver-, lung-, and heart transplant recipients Stable immunosuppressive treatment for ≥3 months No signs of acute graft rejection Patients who reside in Denmark Informed written consent obtained Exclusion Criteria for OTRs: Patients with concomitant bone marrow transplantation Full hysterectomy Inclusion Criteria for Control group: Able patients aged ≥18 years No known immunosuppressive therapy or -condition Patients who reside in Denmark Informed written consent obtained Exclusion Criteria for Control group: - Full hysterectomy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Male organ transplant recipients<br>600 men with a solid organ transplant (heart, lung, liver, kidney or pancreas) | Other: No intervention<br>* The study is an observational study without intervention.<br>|
| Female organ transplant recipients<br>600 women with a solid organ transplant (heart, lung, liver, kidney or pancreas) | Other: No intervention<br>* The study is an observational study without intervention.<br>|
| Female immunocompetent controls<br>600 immunocompetent women without organ transplant or other immunosuppressive conditions/treatments | Other: No intervention<br>* The study is an observational study without intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in prevalence, incidence and persistence of cervical HPV infection in female OTRs compared to immunocompetent controls. | Number of women with cervical HPV infection measured by PCR test. | Evaluated at baseline and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in prevalence of oral HPV infection in female OTRs compared to immunocompetent controls. | Number of women with oral HPV infection measured by PCR test. | Evaluated at baseline | 
| Correlations between lifestyle factors, clinical factors and occurrence of cervical HPV infection in female OTRs. | Lifestyle factors determined by questionnaire. Clinical factors from medical records. Number of women with cervical HPV infection measured by PCR test. | Evaluated at baseline | 
| Correlations between lifestyle factors, clinical factors and occurrence of oral HPV infection in female OTRs. | Lifestyle factors determined by questionnaire. Clinical factors from medical records. Number of women with oral HPV infection measured by PCR test. | Evaluated at baseline | 
| Difference in prevalence and incidence of HPV-related dysplasia and cancer in female OTRs compared to immunocompetent controls. | Number of women with HPV-related dysplasia and HPV-related cancer from registries using registry linkage. | Evaluated at baseline and during up to 15 years after baseline. | 
| Correlations between lifestyle factors, clinical factors and prevalence of skin dysplasia and cancer in OTRs. | Lifestyle factors determined by a questionnaire. Clinical factors from medical records. Skin dysplasia and skin cancer assessed by clinical evaluation and by non-invasive imaging. | Evaluated at baseline | 
| Correlation between Vitamin D and prevalence of skin dysplasia and cancer in OTRs. | Vitamin D from blood sample analysis. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging. | Evaluated at baseline | 
| Correlations between skin pigmentation, facial solar lentigines and prevalence of skin dysplasia and cancer in OTRs. | Skin pigmentation measured with skin reflectance. Facial solar lentigines measured by photographs. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging. | Evaluated at baseline | 
| Correlation between prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs. | Number of women with cervical HPV infection measured by PCR test. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging. | Evaluated at baseline | 
| Correlations between history of herpes zoster, prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs. | Number of women with history of herpes zoster determined by questionnaire. Number of women with cervical HPV infection measured by PCR test. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging. | Evaluated at baseline | 
| Difference in prevalence and incidence of skin cancer in female OTRs compared to immunocompetent controls. | Number of women with skin cancer from registries using registry linkage | Evaluated at baseline and during up to 15 years after baseline. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Organ transplant recipient, Skin cancer, Skin dysplasia, Human papillomavirus, HPV-related dysplasia, HPV-related cancer, HPV