Importance: Patients with immunosuppression have a higher incidence of cutaneous squamous cell carcinoma (cSCC) and often present with more aggressive, multifocal disease. Objectives: To determine the risks for mortality in patients with cSCC and immunosuppression compared with nonimmunosuppression and to compare the difference in mortality risk based on the cause of immunocompromise. Design, Setting, and Participants: This retrospective cohort study of patients with cSCC of the head and neck recruited participants from a tertiary cancer care center. Patients who underwent no treatment, wide local excision, or biopsy of the lesions were eligible for inclusion from January 1, 1995, to September 30, 2015. Data were analyzed from March 21, 2018, to April 4, 2019. Exposures: Immunocompromise, defined as having solid organ transplant, stem cell transplant, hematopoetic malignant disease, autoimmune disease requiring treatment with immunosuppressive therapy, type 1 or 2 diabetes treated with insulin, HIV or AIDS, or other hematoproliferative disorder. Main Outcomes and Measures: Patients were divided into 2 groups according to their immune status (immunosuppression vs no immunosuppression). The primary outcome measure was disease-specific survival. A Cox proportional hazards regression model was used to determine the association of immune status with disease outcome. Results: A total of 796 patients (680 men [85.4%]; median age, 69 [range, 27-98] years), including 147 with and 649 without immunosuppression (IS and non-IS groups, respectively), constituted the final cohort. In the IS group, 77 (52.4%) had diabetes, 39 (26.5%) had lymphoma or leukemia, 25 (17.0%) had an organ or stem cell transplant, and 3 (2.0%) had HIV. Five-year disease-specific survival was 68.2% in the IS group compared with 84.1% in the non-IS group (difference, 15.9%; 95% CI, 3.5%-27.4%). Immunosuppression was independently associated with worse disease-specific survival (hazard ratio, 2.32; 95% CI, 1.53-3.50). Conclusions and Relevance: This study's findings suggest that immunosuppression is independently associated with a worse outcome in cSCC, with a 2.32 times increased risk of disease-specific death after adjusting for age, history of skin cancer, recurrent or persistent disease status, disease stage, and treatment.
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