Incidence of and Risk Factors for Keratinocyte Carcinoma After Pediatric Solid Organ Transplant

Keratinocyte carcinoma (KC), including squamous and basal cell carcinoma, is the most prevalent cancer after solid organ transplant.¹ It is associated with 30- to 52-fold higher mortality rates and increased morbidity in adult transplant recipients.¹ To ascertain the incidence and risk factors for KC after pediatric transplant, we performed a population-based inception cohort study using administrative health data with a health insurance claims-based algorithm.

The Institute for Clinical Evaluative Sciences (ICES) approved this cohort study and waived patient informed consent because only deidentified data were used. Participants resided in Ontario, Canada, and received their first solid organ transplant at younger than age 18 years from 1991 to 2004 at a quaternary care hospital. The KC diagnosis was obtained from the Ontario Health Insurance Plan database, which includes covered care provided throughout Ontario, using a validated algorithm.² Cumulative incidence of posttransplant KC was calculated, accounting for competing risk of death. We calculated sex- and age-adjusted standardized incidence ratio for KC in transplant recipients compared with the general population in Ontario. A multivariable, cause-specific hazards model was used to estimate the rate of KC, with adjustment for patient, transplant, and health services-related factors. Data analysis was performed from May 25, 2021, to December 1, 2021.

Of 951 transplant recipients (514 male [54.0%] and 437 female [46.0]% individuals) with a mean (SD) age at transplant of 7.8 (6.2) years included in the study (Table), 400 (42.1%) received kidney, 283 (29.8%) received liver, 218 (22.9%) received heart, and 36 (3.8%) received lung transplants. Fifteen posttransplant KCs (10 patients [1.1%]) were reported a mean (SD) of 13.1 (5.1) years after transplant, with none reported in the first 4 years. The mean (SD) age at KC diagnosis was 25.2 (6.7) years. Eighty percent of patients with KC (n = 8 of 10) had kidney transplantation, and 50% (n = 5) died within a median (IQR) follow-up of 14.0 (8.7-20.6) years. Most kidney transplant recipients with KC still had functional graft at the time of KC diagnosis.

Overall, the incidence of KC was increased compared with that of the general population in Ontario (standardized incidence ratio, 9.09; 95% CI 5.48-15.08) (Figure). Adjusted hazard ratios for KC increased with time since transplant: 3.63 (95% CI, 0.51-25.77) for 1 to 5 years, 5.14 (95% CI, 1.28-20.55) for 5 to 10 years, and 4.80 (95% CI, 2.29-10.08) for 10 years or more vs the general population.

Previous studies reported primarily on internal malignant neoplasms in pediatric transplant recipients, with limited data on KC. The increased risk of KC may be attributed to oncogenic viral infections, decreased host immunosurveillance, and carcinogenicity of immunosuppressants.³ Furthermore, the risk increases with greater duration of immunosuppression, especially relevant in kidney transplant recipients.³ Findings of the present study expand on previous studies of risk factors associated with KC, such as White race and male sex.^3-5 Male individuals may have a higher risk for KC owing to higher occupational UV radiation exposure and sex-based differences in adherence to sun protective measures.⁵ Pre-transplant KC was identified as a risk factor for posttransplant KC in a cohort study of 10 198 adult solid organ transplant recipients¹; however, this risk was not present in the cohort of the present study owing to the young age at transplant.

This study has limitations. Incidence of KC may be underestimated owing to undiagnosed or unreported KCs.⁶ In addition, race data were only available for a subset of patients. The small number of KCs precluded extensive analysis of risk factors. Sun protection practices were not captured, and cumulative drug exposure associated with KC was not available.

In this cohort study, we found an increased risk of KC in pediatric transplant recipients vs the general population of Ontario. The data highlight the need for further studies to confirm the risk of KC and to help support recommendations for education about sun protection and KC surveillance in this population.

Accepted for Publication: April 14, 2022.

Published Online: June 8, 2022. doi:10.1001/jamadermatol.2022.1960

Corresponding Author: Cathryn Sibbald, MD, MSc, Division of Pediatric Dermatology, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada (cathryn.sibbald@sickkids.ca).

Author Contributions: Dr Sibbald had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sachdeva, Lara-Corrales, Pope, Chan, Sibbald.

Acquisition, analysis, or interpretation of data: Sachdeva, Lara-Corrales, Chan, Parekh, Kitchlu, Sibbald.

Drafting of the manuscript: Sachdeva, Pope, Sibbald.

Critical revision of the manuscript for important intellectual content: Sachdeva, Lara-Corrales, Chan, Parekh, Kitchlu, Sibbald.

Statistical analysis: Sachdeva, Parekh.

Obtained funding: Sachdeva, Lara-Corrales.

Administrative, technical, or material support: Sachdeva, Kitchlu.

Supervision: Lara-Corrales, Sibbald.

Conflict of Interest Disclosures: Ms Sachdeva reported receiving a Creative Professional Activity Grant from the Department of Paediatrics, at the Hospital for Sick Children and grants from the Pediatric Dermatology Research Alliance and the SickKids Research Institute during the conduct of the study. Dr Pope reported receiving personal fees from Novartis, Boeringher Ingelheim, Sanofi, Timber, and AbbVie outside the submitted work and being a contributor to UptoDate. Dr Kitchlu reported administration of funds for the University Health Network Onco-Nephrology Fellowship Program, which wer provided by Amgen and Janssen Pharmaceuticals. Dr Sibbald reported receiving grants from the Pediatric Dermatology Research Alliance and grants from Paediatric Consultants Partnership during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by a grant from the Pediatric Dermatology Research Alliance (Ms Sachdeva) a Hospital for Sick Children Creative Professional Activity grant (Dr Sibbald).

Role of the Funder/Sponsor: The funder or sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.