The Organ Transplant Recipient HPV and Skin Cancer Study

• ClinicalTrials.gov Identifier: NCT05284877
• Recruitment Status: Recruiting
• First Posted: March 17, 2022
• Last Update Posted: April 1, 2022
• Sponsor: Merete Haedersdal
• Collaborators: Danish Cancer Society; Zealand University Hospital; Vejle Hospital; Herlev and Gentofte Hospital; Rigshospitalet, Denmark
• Information provided by (Responsible Party): Merete Haedersdal, Bispebjerg Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Solid Organ Transplant Recipient; Skin Cancer; Skin Dysplasia; HPV Infection; Cervical Intraepithelial Neoplasia; Cervical Cancer; HPV-Related Malignancy	Other: No intervention

Detailed Description:

AIMS

The specific research objectives of this study are:

1. To investigate the overall and type-specific prevalence, incidence and persistence of cervical HPV infection in OTRs compared to immunocompetent controls.
2. To investigate the overall and type-specific prevalence of oral HPV infection in female OTRs compared to immunocompetent controls.
3. To determine the role of lifestyle and clinical factors for the occurrence of cervical and oral HPV infection in female OTRs.
4. To investigate the prevalence and incidence of HPV-related dysplasia and cancer in female OTRs compared with immunocompetent controls.
5. To determine the role of lifestyle, clinical and organ transplantation-related factors for the prevalence and incidence of skin dysplasia in OTRs.
6. 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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 1800 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 12 Months
• Official Title: The Organ Transplant Recipient HPV and Skin Cancer Study
• Actual Study Start Date: March 10, 2022
• Estimated Primary Completion Date: April 2027
• Estimated Study Completion Date: April 2027

Groups and Cohorts

Group/Cohort	Intervention/treatment
Male organ transplant recipients; 600 men with a solid organ transplant (heart, lung, liver, kidney or pancreas)	Other: No intervention; The study is an observational study without intervention.
Female organ transplant recipients; 600 women with a solid organ transplant (heart, lung, liver, kidney or pancreas)	Other: No intervention; The study is an observational study without intervention.
Female immunocompetent controls; 600 immunocompetent women without organ transplant or other immunosuppressive conditions/treatments	Other: No intervention; The study is an observational study without intervention.

Outcome Measures

Primary Outcome Measures :

1. Difference in prevalence, incidence and persistence of cervical HPV infection in female OTRs compared to immunocompetent controls. [ Time Frame: Evaluated at baseline and month 12 ]
   Number of women with cervical HPV infection measured by PCR test.

Secondary Outcome Measures :

1. Difference in prevalence of oral HPV infection in female OTRs compared to immunocompetent controls. [ Time Frame: Evaluated at baseline ]
   Number of women with oral HPV infection measured by PCR test.
2. Correlations between lifestyle factors, clinical factors and occurrence of cervical HPV infection in female OTRs. [ Time Frame: Evaluated at baseline ]
   Lifestyle factors determined by questionnaire. Clinical factors from medical records. Number of women with cervical HPV infection measured by PCR test.
3. Correlations between lifestyle factors, clinical factors and occurrence of oral HPV infection in female OTRs. [ Time Frame: Evaluated at baseline ]
   Lifestyle factors determined by questionnaire. Clinical factors from medical records. Number of women with oral HPV infection measured by PCR test.
4. Difference in prevalence and incidence of HPV-related dysplasia and cancer in female OTRs compared to immunocompetent controls. [ Time Frame: Evaluated at baseline and during up to 15 years after baseline. ]
   Number of women with HPV-related dysplasia and HPV-related cancer from registries using registry linkage.
5. Correlations between lifestyle factors, clinical factors and prevalence of skin dysplasia and cancer in OTRs. [ Time Frame: Evaluated at baseline ]
   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.
6. Correlation between Vitamin D and prevalence of skin dysplasia and cancer in OTRs. [ Time Frame: Evaluated at baseline ]
   Vitamin D from blood sample analysis. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging.
7. Correlations between skin pigmentation, facial solar lentigines and prevalence of skin dysplasia and cancer in OTRs. [ Time Frame: Evaluated at baseline ]
   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.
8. Correlation between prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs. [ Time Frame: Evaluated at baseline ]
   Number of women with cervical HPV infection measured by PCR test. Skin dysplasia and skin cancer assessed by clinical evaluation and non-invasive imaging.
9. Correlations between history of herpes zoster, prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs. [ Time Frame: Evaluated at baseline ]
   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.
10. Difference in prevalence and incidence of skin cancer in female OTRs compared to immunocompetent controls. [ Time Frame: Evaluated at baseline and during up to 15 years after baseline. ]
    Number of women with skin cancer from registries using registry linkage

Biospecimen Retention:   Samples With DNA

Whole blood samples from all OTRs at baseline and 6 months after the baseline visit.

Cervico-vaginal self-sample from all female OTRs and controls at baseline and 12 months after the baseline visit.

Oral mouthwash sample from all female OTRs and controls at baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: A total of 1200 OTRs, 600 male and 600 female OTRs, will be included. An immunocompetent control group of women (n=600) will be recruited.
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

OTRs attending regular skin cancer screening at the Departments of Dermatology at Bispebjerg Hospital (BBH), Gentofte University Hospital (GEH) and Zealand University Hospital Roskilde (ZUH) are eligible for inclusion in the cohort. Approximately 850 OTR patients are currently attending dermatologic screening at BBH, 400 at GEH, and 450 at ZUH.

A total of 1200 OTRs (600 men and 600 women) will be included. Patient inclusion will be distributed between the three dermatologic departments.

An immunocompetent control group of women (n=600) will be recruited from the outpatient clinic at the Departments of Dermatology BBH, GEH and ZUH. Controls will be matched with female OTRs according to age (categories 18-29 years, 30-39 years, 40-49 years, 50-59 years, 60-69 years, ≥70 years).

Criteria

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

Contacts and Locations

Contacts

Contact: Lene Rask; +45 23359940; lene.rask.01@regionh.dk

Locations

Denmark

Department of Dermatology, Bispebjerg Hospital; Recruiting

Copenhagen NV, Region Hovedstaden, Denmark, 2400

Contact: Merete Hædersdal, DMSc, MD mhaedersdal@dadlnet.dk

Contact: Lene Rask, PhD lene.rask.01@regionh.dk

Department of Dermatology and Allergy, Herlev og Gentofte Hospital; Not yet recruiting

Hellerup, Region Hovedstaden, Denmark, 2900

Contact: Claus Zachariae, DMSc, MD claus.zachariae@regionh.dk

Department of Dermatology, Zealand University Hospital; Not yet recruiting

Roskilde, Region Sjælland, Denmark, 4000

Contact: Gregor Jemec, DMSc, MD gbj@regionsjaelland.dk

Sponsors and Collaborators

Merete Haedersdal

Danish Cancer Society

Zealand University Hospital

Vejle Hospital

Herlev and Gentofte Hospital

Rigshospitalet, Denmark

Investigators

• Principal Investigator: Merete Hædersdal, DMSc, MD; Bispebjerg Hospital

More Information

• Responsible Party: Merete Haedersdal, Principal investigator, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT05284877
• Other Study ID Numbers: HPV Skin Cancer OTR; Journal-nr.: H-21038387 ( Other Identifier: National Committee on Health Research Ethics (NVK; Denmark) )
• First Posted: March 17, 2022
• Last Update Posted: April 1, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merete Haedersdal, Bispebjerg Hospital:

Organ transplant recipient; Skin cancer; Skin dysplasia; Human papillomavirus; HPV-related dysplasia; HPV-related cancer; HPV

Additional relevant MeSH terms:

Papillomavirus Infections; Skin Neoplasms; Cervical Intraepithelial Neoplasia; Neoplasms; Neoplasms by Site; Skin Diseases; Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections