## Risk Factors for Cutaneous Squamous Cell Carcinoma **Key Point:** Chronic ultraviolet (UV) radiation exposure is the single most important and common risk factor for cutaneous SCC globally and in India. ### Major Risk Factors | Risk Factor | Mechanism | Relative Risk | |---|---|---| | Chronic UV exposure | DNA damage, p53 mutations | Highest | | Fair skin phototype | Reduced melanin protection | High | | Age > 50 years | Cumulative UV exposure | High | | Immunosuppression | Impaired T-cell surveillance | Moderate-High | | HPV infection | Viral oncoproteins (E6, E7) | Moderate | | Chronic wounds/scars | Chronic inflammation (Marjolin ulcer) | Moderate | | Arsenic exposure | Occupational/environmental | Low-Moderate | | Radiation therapy | Ionizing radiation | Low-Moderate | **High-Yield:** In the Indian subcontinent, where solar UV index is high year-round, chronic sun exposure accounts for >80% of cutaneous SCCs, particularly in outdoor workers and farmers. **Clinical Pearl:** SCCs arising in sun-exposed areas (face, neck, dorsal hands, ears) have better prognosis than those in non-sun-exposed or chronically inflamed sites (lower lip, genitals, chronic ulcers). ### Pathogenesis UV radiation causes thymine dimers and 6-4 photoproducts → p53 mutations → loss of apoptosis and cell cycle control → malignant transformation over years to decades. 
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