Clinical trial NCT05284877: The Organ Transplant Recipient HPV and Skin Cancer Study
Official title: The Organ Transplant Recipient HPV and Skin Cancer Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Solid Organ Transplant Recipient
Skin Cancer
Skin Dysplasia
HPV Infection
Cervical Intraepithelial Neoplasia
Cervical Cancer
HPV-Related Malignancy
Keywords: Organ transplant recipient
Skin cancer
Skin dysplasia
Human papillomavirus
HPV-related dysplasia
HPV-related cancer
HPV
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
name: Zealand University Hospital
name: Vejle Hospital
name: Herlev and Gentofte Hospital
name: Rigshospitalet, Denmark
First posted: 2022-03-17
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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 900 OTRs (300 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).

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, 300 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: 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, 300 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.

Eligibility 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

Primary outcomes:
measure: Difference in prevalence, incidence and persistence of cervical HPV infection in female OTRs compared to immunocompetent controls.
timeFrame: Evaluated at baseline and month 12
Secondary outcomes:
measure: Difference in prevalence of oral HPV infection in female OTRs compared to immunocompetent controls.
timeFrame: Evaluated at baseline
measure: Correlations between lifestyle factors, clinical factors and occurrence of cervical HPV infection in female OTRs.
timeFrame: Evaluated at baseline
measure: Correlations between lifestyle factors, clinical factors and occurrence of oral HPV infection in female OTRs.
timeFrame: Evaluated at baseline
measure: Difference in prevalence and incidence of HPV-related dysplasia and cancer in female OTRs compared to immunocompetent controls.
timeFrame: Evaluated at baseline and during up to 15 years after baseline.
measure: Correlations between lifestyle factors, clinical factors and prevalence of skin dysplasia and cancer in OTRs.
timeFrame: Evaluated at baseline
measure: Correlation between Vitamin D and prevalence of skin dysplasia and cancer in OTRs.
timeFrame: Evaluated at baseline
measure: Correlations between skin pigmentation, facial solar lentigines and prevalence of skin dysplasia and cancer in OTRs.
timeFrame: Evaluated at baseline
measure: Correlation between prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs.
timeFrame: Evaluated at baseline
measure: Correlations between history of herpes zoster, prevalence of cervical HPV infection and prevalence of skin dysplasia and cancer in OTRs.
timeFrame: Evaluated at baseline
measure: Difference in prevalence and incidence of skin cancer in female OTRs compared to immunocompetent controls.
timeFrame: Evaluated at baseline and during up to 15 years after baseline.
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Department of Dermatology, Bispebjerg Hospital
state: Region Hovedstaden
city: Hellerup
country: Denmark
facility: Department of Dermatology and Allergy, Herlev og Gentofte Hospital
state: Region Hovedstaden
city: Roskilde
country: Denmark
facility: Department of Dermatology, Zealand University Hospital
state: Region Sjælland
Study officials:
affiliation: Bispebjerg Hospital
name: Merete Hædersdal, DMSc, MD
role: PRINCIPAL_INVESTIGATOR
References: