title: Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients.
abstract: BACKGROUND
  Skin cancer, in particular squamous cell carcinoma (SCC), is the most common malignancy after solid-organ transplantation. SCC has been reported in immunosuppressed patients receiving voriconazole, but the agent has not been shown to be a risk factor. Universal voriconazole prophylaxis and alemtuzumab induction are standard in our lung transplant program.
  
  
  METHODS
  We performed a retrospective, case-control study (matched 1:3) among lung transplant recipients at our center from 2003 to 2008.
  
  
  RESULTS
  SCC was diagnosed in 3.1% (17 of 543) of patients at a median follow-up of 36 months. Median time to development of SCC was 19 months post-transplant. Risk factors for SCC by univariate analysis included older age (p = 0.02), residence in locations with high levels of sun exposure (p = 0.0001), single-lung transplant (p = 0.02) and duration (p = 0.03) and cumulative dose (p = 0.03) of voriconazole. Duration of voriconazole (hazard ratio [HR] = 2.1; p = 0.04) and residence in locations with high sun exposure (HR = 3.8; p = 0.0004) were independent risk factors by multivariate analysis. SCC lesions were located on the head and neck in 94% of cases, and 53% had multiple lesions. All patients were treated with surgery. At least one independent lesion developed subsequently in 47% of patients. Local spread and distant metastases each occurred in 7% of cases. There were no deaths among the cases.
  
  
  CONCLUSIONS
  Voriconazole exposure is a risk factor for SCC after lung transplantation, particularly among older patients living in areas with high sun exposure. Voriconazole should be used cautiously in these patients.
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors.forename: Aniket
authors.initials: A
authors.lastname: Vadnerkar
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Dimitra
authors.initials: D
authors.lastname: Mitsani
authors.forename: Maria
authors.initials: M
authors.lastname: Crespo
authors.forename: Joseph
authors.initials: J
authors.lastname: Pilewski
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Christian
authors.initials: C
authors.lastname: Bermudez
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Kwak
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Silveira
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009181:Mycoses / Q000517:prevention & control; D009894:Opportunistic Infections / Q000517:prevention & control; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology*; D013472:Sunlight / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole