Viral Reactivation and Skin Cancer

Skin Cancer Clinical Trial

Official title:

Association of Viral Reactivation and Skin Cancer in Organ Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395562
• Other study ID #: FUP063
• Status: Completed
• Phase: N/A
• First received: March 17, 2015
• Last updated: July 11, 2016
• Start date: January 2008
• Est. completion date: June 2016

Study information

• Verified date: July 2016
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Observational

Clinical Trial Summary

Several studies show that the incidence of skin cancer parallels the length and depth of immunosuppression. This study will analyze the correlation of viral reactivation and skin cancer in organ transplant recipients.

Description:

Squamous Cell Carcinoma of the skin (SCC) affects people in high numbers worldwide. While a yearly increase of over 2 million patients, who develop cancer, is recorded, organ transplant recipients (OTR) have a 60- to 100-fold higher risk of developing skin cancer. In OTRs, skin cancer is the most frequent tumor that appears, whereas 95% are nonmelanoma skin cancer cells: squamous cells or basal cell carcinomas. All OTRs need to be treated lifelong with immunosuppressants in order to prevent the rejection of the transplanted organ. However, this immunosuppressive treatment leads to a decrease of immunity, and therefore, cancer cells are able to proliferate easier.

Several studies show that the incidence of skin cancer parallels the length and depth of immunosuppression. The appearance of CD4 in OTRs with cutaneous carcinomas is significantly lower compared to those without skin lesions. Various findings have shown a positive correlation of the period of exposure to immunosuppressants and the risk of skin cancer. However, little is known about the dose or the type of drug is responsible for skin cancer. The uptake of three immunosuppressive medicaments compared to the uptake of two results in a 3-fold increased risk of developing cancer. The consequence of the immunosuppressive therapy is reversible; patients who stop immunosuppressive treatment often show a decrease in skin cancer. The highest risk for organ rejection is during the first three months after transplantation. Therefore, an increased dose of immunosuppressors is used during this time.

In addition to cancer, a high increase of viral infections and reactivations is seen in OTRs. Over 90% of the population carries herpesviruses. The risk of viral infection and reactivation is much higher in OTRs. While inducing a decrease in immunosurveillance, herpesvirus can spread easier.

Herpesvirus infections due to the eight human herpes viruses (HHV) are more frequent by immunosuppression in OTRs. Once a patient is infected with one of the human herpesvirus types (Herpes simplex viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6 and 7, or Kaposi's sarcoma-associated herpesvirus), the virus is able to establish a latent, non-productive infection and maintains the capacity for a life-long reactivation. Due to the decrease of immunity, OTRs are highly susceptible to activate this latent herpesviral infection, which is a critical aspect of the immunosuppressive treatment. The risk of the reactivation of Cytomegalovirus and Epstein-Barr virus in OTRs is much higher compared to the general population.

Taking the above discussed findings together, the investigators hypothesize that viral infections and reactivations correlate positively with skin cancer in OTRs. Furthermore, the investigators think that viral reactivation and infection can be used as a marker for a later incidence of skin cancer. While virus infections and reactivations appear early, OTRs become affected by SCC in the early and in the late period after the transplantation. The investigators thus aim to analyze existing data from the STCS and its nested studies to test these hypotheses: To assess the correlation of viral replication and skin cancer in organ transplant recipients and to assess viral replication as predictor for skin cancer. The investigators are interested in all data available from other studies of the STCS and to divide all organ transplant recipients e.g. for CMV in four groups: no replication, a larger group who show asymptomatic viral replication, some of them with viral syndrome and the ones with proven disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: June 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• oral and written consent to inclusion

• recipient of solid organ transplant

Exclusion Criteria:

• withdrawal of inform consent

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Infection Reactivation
• Skin Cancer
• Skin Neoplasms

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Dermatology	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The correlation of skin cancer with viral reactivation in organ transplant recipients		10 years	No
Secondary	The association of viral reactivation and infection in the first year and skin cancer in the following years. Can one be used as a marker for the other one?		10 years	No