Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens
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Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study.
The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California.
We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period.
We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p < 0.001). However, irrespective of race, skin cancer development was significantly greater in lung compared with liver transplant recipients (20.0% vs. 3.2%, p < 0.001). The standard immunosuppressive and prophylactic regimens were mycophenolate mofetil and tacrolimus based for both transplants. Mycophenolate mofetil was maintained throughout the course in lung transplant patients, whereas this agent was reduced and terminated when possible in liver transplant recipients. In addition, during the years examined, voriconazole, a known photosensitizing agent, was used in lung transplant recipients to prevent aspergillosis.
Fair skin type increases post-transplant skin cancer development, irrespective of the immunosuppressive regimen. A higher risk of skin cancer is associated with different regimens; in particular photosensitizing agents may increase risk in transplant recipients.
The authors acknowledge Griselda Hagmaier, MBA, MHA for administrative support in the process of obtaining study approval. Findings of this study have been presented in part at the American Academy of Dermatology 2018 annual meeting in San Diego, California by Cohen et al. and Krivitskiy et al.
Compliance with Ethical Standards
No sources of funding were received for the preparation of this article.
Conflict of interest
Brandon E. Cohen, Igor Krivitskiy, Sarah Bui, Kevin Forrester, Jeffrey Kahn, Richard Barbers, and Binh Ngo have no conflicts of interest that are directly relevant to the contents of this article.
The Institutional Review Board of the University of Southern California approved this study.
Consent to participate
Informed consent was not obtained because of the retrospective nature of this study and the determination of lack of potential harm to subjects.
- 1.Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348(17):1681–91.Google Scholar
- 2.Hanlon A, Colegio OR. The cutting edge of skin cancer in transplant recipients: scientific retreat of international transplant Skin Cancer Collaborative and Skin Cancer in Organ Transplant Patients Europe. Am J Transplant. 2014;14(5):1012–5.Google Scholar
- 3.Ho WL, Murphy GM. Update on the pathogenesis of post-transplant skin cancer in renal transplant recipients. Br J Dermatol. 2008;158(2):217–24.Google Scholar
- 4.Alam M, Brown RN, Silber DH, Mullen GM, Feldman DS, Oren RM, et al. Increased incidence and mortality associated with skin cancers after cardiac transplant. Am J Transplant. 2011;11(7):1488–97.Google Scholar
- 5.Chockalingam R, Downing C, Tyring SK. Cutaneous squamous cell carcinomas in organ transplant recipients. J Clin Med. 2015;4(6):1229–39.Google Scholar
- 6.Bouwes Bavinck JN, Euvrard S, Naldi L, Nindl I, Proby CM, Neale R, et al. Keratotic skin lesions and other risk factors are associated with skin cancer in organ-transplant recipients: a case-control study in The Netherlands, United Kingdom, Germany, France, and Italy. J Invest Dermatol. 2007;127(7):1647–56.Google Scholar
- 7.Feist A, Lee R, Osborne S, Lane J, Yung G. Increased incidence of cutaneous squamous cell carcinoma in lung transplant recipients taking long-term voriconazole. J Heart Lung Transplant. 2012;31(11):1177–81.Google Scholar
- 8.Ramsay HM, Fryer AA, Reece S, Smith AG, Harden PN. Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients. Am J Kidney Dis. 2000;36(1):167–76.Google Scholar
- 9.Zwald FO, Spratt M, Lemos BD, Veledar E, Lawrence C, Marshall Lyon G, et al. Duration of voriconazole exposure: an independent risk factor for skin cancer after lung transplantation. Dermatol Surg. 2012;38(8):1369–74.Google Scholar
- 10.Garrett GL, Lowenstein SE, Singer JP, He SY, Arron ST. Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013. J Am Acad Dermatol. 2016;75(1):106–12.Google Scholar
- 11.Hufbauer M, Cooke J, van der Horst GT, Pfister H, Storey A, Akgul B. Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis. Mol Cancer. 2015;14:183.Google Scholar
- 12.Vadnerkar A, Nguyen MH, Mitsani D, Crespo M, Pilewski J, Toyoda Y, et al. 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;29(11):1240–4.Google Scholar
- 13.McLaughlin JM, Equils O, Somerville KT, Aram JA, Schlamm HT, Welch VL, et al. Risk-adjusted relationship between voriconazole utilization and non-melanoma skin cancer among lung and heart/lung transplant patients. Transpl Infect Dis. 2013;15(4):329–43.Google Scholar
- 14.Rashtak S, Dierkhising RA, Kremers WK, Peters SG, Cassivi SD, Otley CC. Incidence and risk factors for skin cancer following lung transplantation. J Am Acad Dermatol. 2015;72(1):92–8.Google Scholar
- 15.Krynitz B, Edgren G, Lindelof B, Baecklund E, Brattstrom C, Wilczek H, et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008: a Swedish population-based study. Int J Cancer. 2013;132(6):1429–38.Google Scholar
- 16.Williams K, Mansh M, Chin-Hong P, Singer J, Arron ST. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis. 2014;58(7):997–1002.Google Scholar
- 17.Cowen EW, Nguyen JC, Miller DD, McShane D, Arron ST, Prose NS, et al. Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole. J Am Acad Dermatol. 2010;62(1):31–7.Google Scholar
- 18.Epaulard O, Villier C, Ravaud P, Chosidow O, Blanche S, Mamzer-Bruneel MF, et al. A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study. Clin Infect Dis. 2013;57(12):e182–8.Google Scholar
- 19.Hamandi B, Fegbeutel C, Silveira FP, Verschuuren EA, Younus M, Mo J, et al. Voriconazole and squamous cell carcinoma after lung transplantation: a multicenter study. Am J Transplant. 2018;18(1):113–24.Google Scholar
- 20.Ibrahim SF, Singer JP, Arron ST. Catastrophic squamous cell carcinoma in lung transplant patients treated with voriconazole. Dermatol Surg. 2010;36(11):1752–5.Google Scholar
- 21.Singer JP, Boker A, Metchnikoff C, Binstock M, Boettger R, Golden JA, et al. High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients. J Heart Lung Transplant. 2012;31(7):694–9.Google Scholar
- 22.Clancy CJ, Nguyen MH. Long-term voriconazole and skin cancer: is there cause for concern? Curr Infect Dis Rep. 2011;13(6):536–43.Google Scholar
- 23.Cho HG, Kuo KY, Xiao K, Batra P, Li S, Tang JY, et al. Azathioprine and risk of multiple keratinocyte cancers. J Am Acad Dermatol. 2018;78(1):27–8.Google Scholar
- 24.Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC. Azathioprine and risk of skin cancer in organ transplant recipients: systematic review and meta-analysis. Am J Transplant. 2016;16(12):3490–503.Google Scholar
- 25.Setshedi M, Epstein D, Winter TA, Myer L, Watermeyer G, Hift R. Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non-melanoma skin cancer in an at-risk population: a cohort study. J Gastroenterol Hepatol. 2012;27(2):385–9.Google Scholar