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Original Investigation
January 23, 2019

Association of HLA Antigen Mismatch With Risk of Developing Skin Cancer After Solid-Organ Transplant

Author Affiliations
  • 1Department of Medicine, Banner University Medical Center, Phoenix, Arizona
  • 2Department of Dermatology, University of California, San Francisco, San Francisco
  • 3Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco
  • 4Department of Quantitative Health Sciences, The Cleveland Clinic Foundation, Cleveland, Ohio
  • 5Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, Ohio
  • 6Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco, San Francisco
JAMA Dermatol. 2019;155(3):307-314. doi:10.1001/jamadermatol.2018.4983
Key Points

Question  What is the association between HLA antigen mismatch and the incidence of skin cancer after a solid-organ transplant?

Findings  In this secondary analysis of a cohort study of 10 649 organ transplant recipients, HLA antigen mismatch between a donor and a recipient was associated with a protective effect against posttransplant skin cancer after adjusting for age, sex, white race/ethnicity, thoracic organ transplant, year of transplant, and pretransplant history of skin cancer. Higher levels of HLA antigen mismatch reduced the risk of skin cancer after a solid-organ transplant in heart and lung transplant recipients.

Meaning  Tumor surveillance mechanisms may be activated by HLA antigen mismatch, and well-matched heart and lung transplant recipients may have a higher risk of skin cancer after transplant.


Importance  Risk factors for the development of skin cancer after solid-organ transplant can inform clinical care, but data on these risk factors are limited.

Objective  To study the association between HLA antigen mismatch and skin cancer incidence after solid-organ transplant.

Design, Setting, and Participants  This retrospective cohort study is a secondary analysis of the multicenter Transplant Skin Cancer Network study of 10 649 adults who underwent a primary solid-organ transplant between January 1, 2003, and December 31, 2003, or between January 1, 2008, and December 31, 2008. These participants were identified through the Scientific Registry of Transplant Recipients standard analysis files, which contain data collected mostly by the Organ Procurement and Transplantation Network. Participants were matched to skin cancer outcomes by medical record review. This study was conducted from August 1, 2016, to July 31, 2017.

Main Outcomes and Measures  The primary outcome was time to diagnosis of posttransplant skin cancer, including squamous cell carcinoma, melanoma, and Merkel cell carcinoma. The HLA antigen mismatch was calculated based on the 2016 Organ Procurement and Transplantation Network guidelines. Risk of skin cancer was analyzed using a multivariate Cox proportional hazards regression model.

Results  In total, 10 649 organ transplant recipients (6776 men [63.6%], with a mean [SD] age of 51 [12] years) contributed 59 923 years of follow-up. For each additional mismatched allele, a 7% to 8% reduction in skin cancer risk was found (adjusted hazard ratio [HR], 0.93; 95% CI, 0.87-0.99; P = .01). Subgroup analysis found the protective effect of HLA antigen mismatch to be statistically significant in lung (adjusted HR, 0.70; 95% CI, 0.56-0.87; P = .001) and heart (adjusted HR, 0.75; 95% CI, 0.60-0.93; P = .008) transplant recipients but not for recipients of liver, kidney, or pancreas. The degree of HLA-DR mismatch, but not HLA-A or HLA-B mismatch, was the most statistically significant for skin cancer risk (adjusted HR, 0.85; 95% CI, 0.74-0.97; P = .01).

Conclusions and Relevance  The HLA antigen mismatch appears to be associated with reductions in the risk of skin cancer after solid-organ transplant among heart and lung transplant recipients; this finding suggests that HLA antigen mismatch activates the tumor surveillance mechanisms that protect against skin cancer in transplant recipients and that skin cancer risk may be higher in patients who received a well-matched organ.