From the Guidelines
Squamous cell carcinoma of the ocular surface is a multistep process involving genetic mutations and cellular transformation, with key risk factors including ultraviolet radiation exposure, human papillomavirus infection, and immunosuppression, as noted in recent studies 1. The pathophysiology of squamous cell carcinoma (SCC) of the ocular surface begins with dysplastic changes in the epithelium, progressing from mild to severe dysplasia before developing into carcinoma in situ and eventually invasive SCC.
- Key risk factors include:
- Ultraviolet radiation exposure, which causes DNA damage and p53 gene mutations
- Human papillomavirus infection (particularly HPV-16 and HPV-18)
- Immunosuppression
- Chronic inflammation and conditions like xeroderma pigmentosum At the molecular level, the disease involves activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of cell cycle control mechanisms, as discussed in the context of ocular surface squamous neoplasia 1. The transformed cells exhibit increased proliferation, resistance to apoptosis, and the ability to invade surrounding tissues. As the disease progresses, these cells can break through the basement membrane, invade the substantia propria, and potentially metastasize, though ocular surface SCC tends to be locally aggressive rather than widely metastatic, highlighting the importance of early detection and treatment, as outlined in recent guidelines 1. Early detection is crucial as the disease typically begins as a localized lesion that can be effectively treated before invasion occurs, with treatment options including local excision with cryotherapy and/or topical chemotherapeutic agents, such as mitomycin-C or fluorouracil, as recommended by recent studies 1.
From the Research
Pathophysiology of Squamous Cell Carcinoma
The pathophysiology of squamous cell carcinoma (SCC) involves a multistage process of development and progression, characterized by mutations in genes involved in epidermal homeostasis and alterations such as epigenetic modifications, viral infections, or microenvironmental changes 2.
Risk Factors
Several risk factors are associated with the development of SCC, including:
- Advanced age 2, 3
- Cumulative sun exposure 2, 3
- Fair skin 2
- Prolonged immunosuppression 2
- Previous skin cancer diagnoses 2
- Location in the head and neck region 3
- Presence of solar elastosis in the peritumoral tissue 3
- High tumor growth rate 3
- High cumulative smoking exposure 3
Development and Progression
SCC can arise de novo or result from the progression of actinic keratosis, an in situ carcinoma 2. The development of SCC is a gradual process with several histologically and pathologically defined stages 2.
Diagnostic Approaches
Dermoscopy and reflectance confocal microscopy have enhanced the diagnostic accuracy of SCC 2, 4. Histopathology and correct surgical excision remain the gold standard for diagnosis and treatment of SCC 4.
Treatment Options
Treatment options for SCC include surgical excision, radiotherapy, and systemic therapies such as immunotherapy with immune checkpoint inhibitors and epidermal growth factor receptor inhibitors for metastatic and locally advanced SCC 2, 4. Concomitant radiation therapy, 5-fluorouracil infusion, and bolus mitomycin C have been shown to be effective for local control in esophageal squamous cell carcinoma 5.