Overview
Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer and accounts for approximately 20%-25% of all skin tumors 34. While most cases have a favorable prognosis with high cure rates after treatment, cSCC is associated with a significant number of deaths due to its high incidence 6. Challenges arise in locally advanced or metastatic forms, particularly in immunocompromised individuals 4.Diagnosis
Diagnosis is based on clinical presentation and histological confirmation 6.
Risk stratification and staging are important components of diagnosis 6.
Artificial intelligence shows promising diagnostic accuracy for non-melanoma skin cancer, with summary sensitivity of 0.78, specificity of 0.98, and AUC of 0.97 7.Management
For common primary cSCC, first-line treatment is surgical excision with postoperative margin assessment or micrographically controlled surgery 5. Achieving clear surgical margins is paramount for surgically amenable cSCCs 5.
Radiotherapy should be considered as the primary treatment for patients who are not surgical candidates or for non-surgical tumors 5.
For patients with high-risk localized cSCC and clear surgical margins, adjuvant radiotherapy has not shown significant benefit based on current evidence 5.
For cSCC with confirmed regional nodal metastasis, lymph node management is indicated 5.
For advanced stages, immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options, alongside traditional chemotherapy and targeted therapy 4.
Non-surgical treatment options may be considered as alternatives to surgery 1.Special Populations
cSCC primarily appears in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties, presenting challenges in management 4.
Guidelines address diagnosis, prevention, and management in both immunocompetent and immunosuppressed patients 6.Key Recommendations
For common primary cSCC amenable to surgery, surgical excision with postoperative margin assessment or micrographically controlled surgery is the first-line treatment 5. (Evidence: Expert opinion)
Achieving clear surgical margins is the most important treatment consideration for patients with cSCCs amenable to surgery 5. (Evidence: Expert opinion)
Radiotherapy should be considered as the primary treatment for non-surgical candidates or non-surgical tumors 5. (Evidence: Expert opinion)
For patients with high-risk localized cSCC with clear surgical margins, current evidence has not shown significant benefit from adjuvant radiotherapy 5. (Evidence: Weak)
Artificial intelligence demonstrates high diagnostic accuracy for non-melanoma skin cancer, with a summary sensitivity of 0.78 and specificity of 0.98 7. (Evidence: Moderate)References
1 Takai T, Kadono T, Fujimoto N, Yoden E, Nomura T, Matsumoto K et al.. Japanese Dermatological Association Guidelines: Clinical Questions of Guidelines for Cutaneous Squamous Cell Carcinoma 2025. The Journal of dermatology 2026. link
2 Weber I, Liao K, Dang T, Shah M, Wehner MR. Sunburn and Cutaneous Squamous Cell Carcinoma: A Meta-Analysis. JAMA dermatology 2025. link
3 Bencomo T, Lee CS. Gene expression landscape of cutaneous squamous cell carcinoma progression. The British journal of dermatology 2024. link
4 Queirolo P, Cinquini M, Argenziano G, Bassetto F, Bossi P, Boutros A et al.. Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology. ESMO open 2024. link
5 Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, van Akkooi A, Bataille V et al.. European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment-Update 2023. European journal of cancer (Oxford, England : 1990) 2023. link
6 Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, van Akkooi A, Bataille V et al.. European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma. Part 1: Diagnostics and prevention-Update 2023. European journal of cancer (Oxford, England : 1990) 2023. link
7 Kuo KM, Talley PC, Chang CS. The accuracy of artificial intelligence used for non-melanoma skin cancer diagnoses: a meta-analysis. BMC medical informatics and decision making 2023. link
8 Pattinson RL, Trialonis-Suthakharan N, Gupta S, Henry AL, Lavallée JF, Otten M et al.. Patient-Reported Outcome Measures in Dermatology: A Systematic Review. Acta dermato-venereologica 2021. link