Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients

J Heart Lung Transplant. 2010 Nov;29(11):1240-4. doi: 10.1016/j.healun.2010.05.022. Epub 2010 Jun 29.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / therapeutic use
  • Carcinoma, Squamous Cell / epidemiology*
  • Case-Control Studies
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lung Transplantation* / immunology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycoses / prevention & control
  • Opportunistic Infections / prevention & control
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / epidemiology*
  • Sunlight / adverse effects*
  • Triazoles / adverse effects*
  • Triazoles / therapeutic use
  • Voriconazole

Substances

  • Antifungal Agents
  • Immunosuppressive Agents
  • Pyrimidines
  • Triazoles
  • Voriconazole