Risk of Keratinocyte Carcinoma Increases With Pediatric Solid Organ Transplant

The rate of keratinocyte carcinoma (KC) was 8 times greater among individuals living in Ontario, Canada, who underwent their first pediatric solid organ transplant before they were 18 years old vs similar outcomes among the province’s general population, according to study findings published recently in JAMA Dermatology.

Cited as the most common form of human cancer, with an established risk of recurrent disease and malignant melanoma, the authors of the present study noted that KC also “is the most prevalent cancer after solid organ transplant. It is associated with 30- to 52-fold higher mortality rates and increased morbidity in adult transplant recipients.”

Data on the 951 patients who underwent transplant and the more than 5 million who did not between 1991 and 2004 were provided by the Ontario Health Insurance Plan database, and a validated algorithm was used to calculate KC incidence that also considered mortality risk from other causes. Analyses took place between May 25, 2021, and December 1, 2021.

Transplant recipients were younger than those who did not undergo a transplant: The mean ages were 7.8 (6.2) and 8.2 (6.4) years, respectively. Further, more of the transplant recipients were male (54.0%) vs the nontransplant cohort (49.8%). The overall median (IQR) follow-up time was close to 3 years shorter in the transplant group, at 11.8 (7.3-8.1) vs 14.0 (8.7-20.6) years.

The most common solid organ transplant was kidney (42.1%), followed by liver (29.8%), heart (22.9%), and lung (3.8%), and the mean age at KC diagnosis was 25.2 (6.7) years. In addition, most instances of KC (80%) were seen among kidney transplant recipients, most of whom still had a functional kidney at KC diagnosis, and 50% died within a median 14 years.

In addition, the rate of multiple instances of KC was close to 4 times greater in the solid-organ transplant group compared with the nontransplant group: 1.1% (10/951) vs 0.3% (17,558/5,276,607); this median follow-up was 13.1 (5.1) years post transplant.

The overall mortality rate was also exceedingly higher in the transplant group compared with the nontransplant group, at 18.9% vs 0.3%; the KC incidence rate was just over 8 times greater (standardized incidence ratio, 9.09; 95% CI, 5.48-15.08), and risk of KC increased with longer time since transplant, with the greatest increased risk associated with 5 to 10 years since transplant:

• 1 to 5 years: 263% (adjusted HR [aHR], 3.63; 95% CI, 0.51-25.77)
• 5 to 10 years: 414% (aHR, 5.14; 95% CI, 1.28-20.55)
• 10 or more years: 380% (aHR, 4.80; 95% CI, 2.29-10.08)

This study’s authors attributed their findings to several potential causes: oncogenic viral infections, decreased host immunosurveillance, and carcinogenicity of immunosuppressants—with risk of developing KC increasing the longer the immunosuppression. They also noted their findings expand on previous research showing a higher KC risk among patients who are male, “owing to higher occupational UV radiation exposure and sex-based differences in adherence to sun protective measures.”

“The data highlight the need for further studies to confirm the risk of KC,” the authors concluded, “and to help support recommendations for education about sun protection and KC surveillance in this population.”

Reference

Sachdeva M, Lara-Corrales I, Pope E, et al. Incidence of and risk factors for keratinocyte carcinoma after pediatric solid organ transplant. JAMA Dermatol. 2022;158(7):828-831. doi:10.1001/jamadermatol.2022.1960