SCRIPT: Skin Change Risk In Patients after Transplant
Research type
Research Study
Full title
Elucidating the transformational role of ß human papillomavirus early region genes in skin of organ transplant recipients and healthy individuals
IRAS ID
161182
Contact name
Girish K Patel
Contact email
Sponsor organisation
Hywel Dda University Health Board
Research summary
Patients who receive an organ transplant often require lifelong immunosuppression to prevent organ rejection. This group of patients have a higher incidence rate of cancer compared to the general population, attributable to reactivation of latent viral infections such as Epstein-Barr virus-associated Hodgkin’s (B-cell) lymphomas. In particular cutaneous squamous cell carcinoma (SCC) is the most common malignancy in organ transplant recipients (OTR), with an approximately 100-fold increased incidence over background risk. Skin cancers affect more than half of organ-transplant recipients and are a major cause of morbidity and mortality.
Beta human papillomaviruses (ßHPVs) are a group of DNA viruses, which have the ability to establish persistent infections in skin. In the healthy individual the immune system suppress viral replication and/or expansion of infected cells. However in immunosuppressed individuals, such as organ transplant recipients, reactivation of latent ßHPVs is responsible for field cancerization: large areas of actinic keratosis, Bowenoid keratosis and Bowens disease. The phenomenon of field cancerisation predisposes to SCC and provides strong evidence to support the role of these viruses in skin cancer development in immunosuppressed individuals.We hypothesise that there may be an indirect link between HPV and SCC formation, which involves field cancerization. It has been shown that ßHPV transgenic mice develop skin keratoses within which SCC develop spontaneously. Since we have also shown that SCC growth is dependent upon skin cancer stem cells defined by the expression of the cell surface protein CD133, we propose to determine whether field cancerization represents early expansion of cancer stem cells or precursors keratinocyte stem cells.
This is a retrospective study involving laboratory based research on 300 participant samples from those with a previous histological diagnosis of actinic keratosis, Bowenoid keratosis or Bowens disease will be used to determine demonstrate ßHPV viral proteins in healthy and OTR patients.
REC name
North West - Preston Research Ethics Committee
REC reference
14/NW/1272
Date of REC Opinion
4 Sep 2014
REC opinion
Favourable Opinion