Risk of merkel cell carcinoma after solid organ transplantation

Abstract

Background: Solid organ transplant recipients have elevated risks of virus-related cancers, in part because of long-term immunosuppression. Merkel cell carcinoma (MCC) is an aggressive skin cancer recently found to have a viral origin, but little is known regarding the occurrence of MCC after transplant.

Methods: We linked the US Scientific Registry of Transplant Recipients with data from 15 population-based cancer registries to ascertain MCC occurrence among 189498 solid organ transplant recipients from 1987 to 2009. Risks for MCC following transplantation were compared with the general population using standardized incidence ratios, and Poisson regression was used to compare incidence rates according to key patient and transplant characteristics. All statistical tests were two-sided.

Results: After solid organ transplantation, overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to 28.7, n = 110). Adjusted risks were highest among older recipients, increased with time since transplantation, and varied by organ type (all P ≤ .007). Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance immunosuppression increased risk, and non-Hispanic white recipients on cyclosporine and azathioprine experienced increasing MCC risk with lower latitude of residence (ie, higher ultraviolet radiation exposure, P = .012).

Conclusions: MCC risk is sharply elevated after solid organ transplant, likely resulting from long-term immunosuppression. Immunosuppressive medications may act synergistically with ultraviolet radiation to increase risk.

Figure 1.

MCC incidence rates among non-Hispanic whites according to maintenance medication type and ultraviolet radiation as measured by quintile of residential A) latitude and B) AVGLO. AVGLO is predicted 30-year average daily total global solar radiation (Wh/km²). Results are presented for transplants associated with maintenance immunosuppression with cyclosporine/azathioprine, tacrolimus/mycophenolate mofetil, and other regimens (see Methods for details). Vertical lines depict 95% confidence intervals of incidence rate estimates (some upper limits are out of range and so are not shown). P _trend values are shown, and P _interaction values are .016 for residential latitude and .086 for AVGLO. Latitude quintiles 4 and 5 are combined because of small numbers (5139 person-years in quintile 5). All statistical tests were two-sided.