Aims: Cutaneous squamous cell carcinoma (cSCC) is particularly prevalent in patients who have underlying medical or iatrogenic immunosuppression (IS). However, the exact definition of IS in the published literature is variable, affecting the interpretation of risk prognostic studies in cSCC.
Methods: To understand the degree of heterogeneity in the definition of IS in cSCC patients, we conducted a systematic review of the literature up to November 2023 using: MEDLINE, EMBASE, and Cochrane. Studies of cSCC that specifically mentioned IS, studies assessing immunosuppression secondary to organ transplant, haematological malignancy, HIV, as well as those receiving immunosuppressive therapy for other inflammatory diseases, were retrieved. The definitions of IS were categorized, and factors associated with study conclusions and study types were included. Descriptive statistics were performed to summarize the findings.
Results: A total of 1057 papers were identified through the database search. Three-hundred and forty-seven articles were evaluated for full-text review, of which 189 fulfilling the search criteria were included. Solid organ transplant patient cohorts were described in 134 (70.9%) studies, 78 (41.3%) described patients with haematological malignancies, and long-term steroid use was analysed in 60 (31.8%) studies.
One-hundred and sixty studies compared multiple causes of IS, of which solid organ transplant (75.0%), haematological malignancy (48.1%), long-term corticosteroid use (35.0%) and human immune-deficiency virus (17.5%) were the most commonly included. Only 48 (25.4%) of studies encompassed other causes of immunosuppression, such as stem cell transplant (7.5%), chronic kidney disease (4.4%), or diabetes (3.1%).
Conclusion(s): The definition of immunosuppression in cSCC is highly variable across the literature. Consensus definition of IS will be necessary to facilitate effective comparative analysis and quantify risk of immunosuppression on the incidence and prognosis of cSCC.