A 68-year-old farmer from rural Maharashtra with fair complexion presents with a hyperkeratotic, indurated nodule on the dorsum of his left hand that has been growing for 6 months. Biopsy confirms squamous cell carcinoma of the skin. What is the most common aetiological factor responsible for this malignancy?

## Aetiology of Cutaneous Squamous Cell Carcinoma **Key Point:** Chronic ultraviolet (UV) radiation exposure, particularly UVB, is the most common aetiological factor for squamous cell carcinoma (SCC) of the skin worldwide, accounting for >90% of cases in sun-exposed populations. ### Epidemiological Evidence - **Cumulative UV exposure** is the primary driver of keratinocyte malignant transformation. - Risk increases dramatically in individuals with: - Fair skin (Fitzpatrick types I–II) - Occupational sun exposure (farmers, outdoor workers) - Tropical/subtropical geography (high UV index) - Advanced age (cumulative dose effect) ### Comparison of Aetiological Factors | Factor | Frequency | Clinical Context | Notes | |--------|-----------|------------------|-------| | **Chronic UV exposure** | >90% | Sun-exposed areas (dorsal hands, face, ears) | Dose-dependent; preventable | | HPV infection | 5–10% | Anogenital, oral SCC; immunocompromised | HPV-16, HPV-18 implicated | | Chronic arsenic | <2% | Occupational/contaminated water | Bowen's disease precedes SCC | | Immunosuppression (post-transplant) | <1% | Organ transplant recipients | 100–250× increased risk vs. general population | | Chronic wounds (Marjolin's ulcer) | <1% | Long-standing ulcers, burn scars | Poor prognosis | **High-Yield:** The dorsal hand location in a farmer is a classic presentation of **UV-induced SCC** — this is the most frequently tested scenario in NEET PG. ### Mechanism of UV-Induced Transformation 1. UVB causes thymine dimers in DNA → p53 mutations ("sunburn cell" apoptosis). 2. Chronic exposure overwhelms DNA repair (nucleotide excision repair). 3. Accumulation of mutations → malignant transformation of keratinocytes. **Clinical Pearl:** SCC arising from chronic UV exposure typically has a better prognosis (5-year survival ~95%) compared to SCC from other aetiologies (e.g., Marjolin's ulcer, 5-year survival ~30%). **Tip:** When a NEET PG stem mentions an outdoor worker (farmer, construction worker) with a skin lesion on sun-exposed skin, immediately think UV-induced SCC.