## Most Common Aetiological Factor in Cutaneous SCC **Key Point:** Chronic ultraviolet (UV) radiation exposure is the single most common aetiological factor for cutaneous squamous cell carcinoma, accounting for approximately 80–90% of cases worldwide. ### Pathophysiology of UV-Induced SCC 1. **UVB radiation** (280–320 nm) penetrates the epidermis and causes direct DNA damage (thymine dimers). 2. **UVA radiation** (320–400 nm) generates reactive oxygen species (ROS) leading to indirect DNA damage. 3. Cumulative sun exposure over decades → multiple mutations in TP53, CDKN2A, and other tumour suppressor genes. 4. Loss of apoptosis → malignant transformation of keratinocytes. ### Risk Factors for UV-Related SCC | Risk Factor | Details | |---|---| | **Cumulative sun exposure** | Occupational exposure (farmers, construction workers, sailors) | | **Fair skin (Fitzpatrick I–II)** | Reduced melanin protection | | **Age** | Peak incidence 6th–8th decade | | **Geography** | Higher incidence near equator (Australia, South Africa) | | **Chronic sun damage** | Actinic keratosis is a precursor lesion | **Clinical Pearl:** The patient's occupation as a farmer with 8 months of non-healing ulcer on sun-exposed dorsal hand is a classic presentation of UV-induced SCC. Dorsal hands and forearms are high-risk sites due to chronic occupational exposure. **High-Yield:** In India, cutaneous SCC incidence is rising due to increased outdoor occupational exposure and limited sun protection awareness. UV exposure remains the dominant risk factor even in tropical climates with high ambient UV index. ### Why Other Factors Are Less Common - **HPV infection:** Associated with SCC of anogenital region and oropharynx; cutaneous SCC is HPV-negative in >95% of immunocompetent patients. - **Immunosuppression:** Increases SCC risk 65–250-fold but is less common than UV exposure in the general population. - **Arsenic exposure:** Historically relevant in certain occupational/geographic settings but rare in modern practice. [cite:Robbins 10e Ch 25]
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