Risk Stratification of Invasive Cutaneous Head/Neck Squamous Cell Carcinomas in Solid Organ Transplant Recipients

Introduction: Head/neck location and immunosuppression are independent risk factors in solid organ transplant recipients (SOTRs) with head and neck cutaneous squamous cell carcinomas (cHNSCC). However, staging systems, which tend to underperform specifically for the immunosuppressed population, differ particularly on the importance of depth of invasion for smaller tumors; we aim to identify the utility of clinicopathologic factors, such as depth of invasion, for risk stratification of cHNSCCs in SOTRs.

Methods: SOTRs who underwent surgery for post-transplant cHNSCCs from 2009-2019 at a single tertiary center were reviewed. Clinicopathologic data were extracted from electronic records. Associations with depth of invasion were tested using unpaired t-tests, ANOVA for transplant type, and univariate Cox regression for age. Survival was evaluated using univariate Cox regression by age at first tumor and at transplant, and Mantel-Cox test by invasion.

Results: Of 77 identified patients, 44 (100% White, 97.8% non-Hispanic, 81.8% male) met criteria. Of the 44 patients, 16 developed deeply invasive cHNSCCs, which extended deep to the subcutis. There was no difference in invasion by sex, race, ethnicity. Transplant type (21 kidney, 6 two organ, 6 heart, 8 liver, 3 lung) had no effect on 5- and 10-year survival after first cHNSCC or risk of developing deeply invasive cHNSCCs. Difference in age at transplant approached significance (p = 0.07), with patients with deeply invasive tumors receiving transplant on average 5.3 years earlier. Age at first tumor and age at transplant were poor predictors of survival. Deep invasion correlated with shorter overall lifespan (p = 0.02) and decreased survival (p = 0.0021).

Conclusions: Sex, race, ethnicity, transplant type, and age at first cHNSCC do not increase risk of developing deeply invasive tumors. Deep invasion is associated with decreased survival, supporting the validity of staging that incorporates this factor even in smaller tumors. Mutation analysis and changes to immunosuppression may further enhance prognostication.