De Novo Carcinoma after Solid Organ Transplantation to Give Insight into Carcinogenesis in General—A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Patients receiving a solid organ transplantation, such as a kidney, liver, or lung transplantation, inevitably have to take drugs to suppress the immune system in order to prevent rejection of the transplanted organ. However, these drugs are known to cause malignancies in the long term. This study focuses specifically on newly developed carcinomas in patients who use those drugs after a solid organ transplantation. This systematic review and meta-analysis of published data show a 20-fold risk to develop a carcinoma after solid organ transplantation compared to the general population, with specifically increased risks in patients who receive cyclosporine or azathioprine. By comparing the different pathways involved in immunosuppression and the occurrence of carcinoma development, new insights can be discovered for future research and understanding of carcinoma development in transplantation patients and the general population as well. ABSTRACT: Immunosuppressive therapy after solid organ transplantation leads to the development of cancer in many recipients. Analysis of the occurrence of different types of de novo carcinomas in relation to specific immunosuppressive drugs may give insight into their carcinogenic process and carcinogenesis in general. Therefore, a systematic search was performed in Embase and PubMed. Studies describing over five de novo carcinomas in patients using immunosuppressive drugs after solid organ transplantation were included. Incidence per 1000 person-years was calculated with DerSimonian–Laird random effects model and odds ratio for developing carcinomas with the Mantel–Haenszel test. Following review of 5606 papers by title and abstract, a meta-analysis was conducted of 82 studies. The incidence rate of de novo carcinomas was 8.41. Patients receiving cyclosporine developed more de novo carcinomas compared to tacrolimus (OR1.56, 95%CI 1.00–2.44) and mycophenolate (OR1.26, 95%CI 1.03–1.56). Patients receiving azathioprine had higher odds to develop de novo carcinomas compared to mycophenolate (OR3.34, 95%CI 1.29–8.65) and head and neck carcinoma compared to tacrolimus (OR3.78, 95%CI 1.11–12.83). To conclude, patients receiving immunosuppressive drugs after solid organ transplantation have almost a 20-fold increased likelihood of developing carcinomas, with the highest likelihood for patients receiving cyclosporine A and azathioprine. Looking into altered immune pathways affected by immunosuppressive drugs might lead to better understanding of carcinogenesis in general.