Table 3.

Summary of high-risk factors for primary squamous cell carcinoma according to recent staging systems and guidelines.

High-Risk Factors	AJCC 8th ed. Classification	BWH Classification	NCCN Guidelines	EADO Guidelines
Patient-related risk factors
Immunosuppression	Not included	Not included	Yes	Yes
Site of prior RT or chronic inflammation	Not included	Not included	Yes	Not included
Neurological symptoms/symptomatic PNI	Yes	Not included	Yes	Yes
Tumor-related clinical risk factors
Large clinical diameter	>2 cm	≥2 cm	≥2 cm area L *	>2 cm
			≥1 cm area M *
			Any for area H *
Anatomical location of primary tumor	Not included	Not included	Area H	Ear, lip, temple
Poorly defined tumor borders	Not included	Not included	Yes	Not included
Rapidly growing tumor	Not included	Not included	Yes	Not included
Recurrent tumor	Not included	Not included	Yes	Not included
Tumor-related radiological risk factors
Bone involvement	Yes	Yes	Not included	Yes
Perineural invasion on imaging	Yes	Yes	Not included	Yes
Tumor-related histological risk factors
Breslow thickness > 6 mm	Yes	Yes	Yes	Yes
Poor differentiation	Not included	Yes	Yes	Yes
High-risk histological subtype	Not included	Not included	Yes	Yes
Perineural invasion	Yes	Yes	Yes	Yes
Lymphatic or vascular invasion	Not included	Not included	Yes	Not included
Invasion beyond subcutaneous fat	Yes	Yes	Yes	Yes

Abbreviations: BWH: Brigham and Women’s Hospital; PNI: perineural invasion; RT: radiotherapy. * Area L: trunk and extremities (excluding hands, nail units, pretibial, ankles, feet); Area H: central face, eyelids, eyebrows, periorbital, nose, lips (cutaneous and vermillion), chin, mandible, preauricular and postauricular skin/sulci, temple, ear, genitalia, hands, and feet; Area M: cheeks, forehead, scalp, neck, and pretibial.