Risk Factors for Squamous Cell Carcinoma

Primary Environmental and Host Risk Factors

Organ transplant recipients demonstrate dramatically elevated SCC rates, making immunosuppression one of the two established major risk factors alongside UV radiation, according to the National Comprehensive Cancer Network 1
Certain genetic syndromes greatly predispose to SCC development, including Albinism, Xeroderma pigmentosum, and Nevoid basal cell carcinoma syndrome, as stated by the National Comprehensive Cancer Network 1
Mutations in tumor suppressor gene p53 appear to be an early common event in cutaneous SCC development, as reported by the National Comprehensive Cancer Network 1
Prior radiation therapy to a site predisposes to subsequent SCC development, according to the National Comprehensive Cancer Network 1, 2

High-risk locations for SCC include the "mask area" of the face, genitalia, mucosal surfaces, and ear, as identified by the National Comprehensive Cancer Network 1, 2
Tumors ≥6 mm in high-risk facial locations indicate increased recurrence risk, according to the National Comprehensive Cancer Network 2
Tumors ≥10 mm in middle-risk locations indicate increased recurrence risk, as stated by the National Comprehensive Cancer Network 2
Tumors ≥20 mm on trunk and extremities indicate high-risk behavior, according to the National Comprehensive Cancer Network 2
Poorly defined or ill-defined tumor borders indicate high-risk behavior, as reported by the National Comprehensive Cancer Network 1, 2
Recurrent tumors carry significantly higher risk than primary tumors, according to the National Comprehensive Cancer Network 1, 2
Rapidly growing tumors indicate high-risk behavior with increased metastasis and mortality risk, as stated by the National Comprehensive Cancer Network 3, 4

Perineural involvement significantly increases risk of recurrence and metastasis, according to the National Comprehensive Cancer Network 5
Adenoid (acantholytic) squamous cell carcinoma indicates increased recurrence/metastasis risk, as reported by the National Comprehensive Cancer Network 3, 4
Adenosquamous (mucin-producing) squamous cell carcinoma indicates increased risk, according to the National Comprehensive Cancer Network 3, 4
Desmoplastic squamous cell carcinoma poses greatly increased risk of both recurrence and metastasis, as stated by the National Comprehensive Cancer Network 3, 4, 5
Invasion into deep reticular dermis or subcutaneous fat (Clark level IV or V) is associated with aggressive behavior, according to the National Comprehensive Cancer Network 3, 4, 5

Basosquamous carcinomas should be conceptualized as squamous cell cancers rather than basal cell cancers, as their metastatic capacity resembles SCC, as reported by the National Comprehensive Cancer Network 3, 4