Squamous Cell Carcinoma: Causes, Symptoms & Treatment

What Is Squamous Cell Carcinoma?

Squamous cell carcinoma (SCC) is a malignant cancer that develops from the flat, scale-like cells of the squamous epithelium. These cells are found in the outer layer of the skin and in the mucous membranes of many organs, including the mouth, throat, esophagus, lungs, cervix, and bladder. SCC is one of the most common cancers worldwide and can be highly treatable when detected early.

Causes and Risk Factors

SCC develops when DNA damage accumulates in squamous epithelial cells, triggering uncontrolled cell growth. Key risk factors include:

• UV radiation: Long-term sun exposure and tanning bed use are the leading causes of cutaneous SCC.
• Tobacco use: Smoking and chewing tobacco significantly increase the risk of SCC in the mouth, throat, larynx, and lungs.
• Human papillomavirus (HPV): Certain HPV strains are strongly linked to SCC of the cervix, oropharynx, and anal region.
• Chronic inflammation or irritation: Persistent wounds, scars, or mucosal changes can raise cancer risk over time.
• Immunosuppression: Individuals with weakened immune systems -- such as organ transplant recipients -- face a substantially higher risk.
• Chemical and radiation exposure: Arsenic, certain industrial chemicals, and ionizing radiation are recognized risk factors.
• Precancerous lesions: Actinic keratoses of the skin are considered precursor lesions to cutaneous SCC.

Symptoms

Symptoms of squamous cell carcinoma depend on the organ affected:

Skin

• Red, scaly, or crusted patches that do not heal
• Firm, raised nodules or plaques on the skin
• Sores or ulcers that bleed or heal poorly
• Changes within existing scars or chronic wounds

Mouth and Throat

• Persistent white or red patches in the oral cavity (leukoplakia, erythroplakia)
• Difficulty swallowing or persistent hoarseness
• Non-healing sores or ulcers in the mouth
• Swelling in the jaw or neck area

Lungs

• Persistent cough, bloody sputum
• Shortness of breath, chest pain

Cervix

• Unusual vaginal bleeding
• Pain during sexual intercourse

Diagnosis

Diagnosis of SCC involves a combination of clinical examination and technical investigations:

• Physical examination: Inspection of the affected skin or mucosal region by a physician.
• Dermatoscopy: Magnified examination of skin lesions using a specialized light instrument.
• Biopsy: Removal of a tissue sample for histological (microscopic) analysis -- the gold standard for confirming diagnosis.
• Imaging: CT scan, MRI, or ultrasound to assess tumor extent and detect possible metastases.
• Endoscopy: For tumors located in the airways, esophagus, or other hollow organs.
• HPV testing and Pap smear: Used for early detection of cervical carcinoma.

Treatment

Treatment depends on the tumor location, stage, and the overall health of the patient:

Surgical Removal

Surgical excision with adequate safety margins is the first-line treatment in most cases. For cutaneous SCC, Mohs micrographic surgery is often used to maximize the removal of cancerous tissue while sparing healthy surrounding skin.

Radiation Therapy

Radiation therapy is used for tumors that cannot be surgically removed, or as adjuvant therapy after surgery to eliminate remaining cancer cells.

Chemotherapy

For advanced or metastatic SCC, chemotherapy -- alone or in combination with other treatments -- may be used. Commonly employed agents include cisplatin and 5-fluorouracil.

Immunotherapy and Targeted Therapy

Modern treatment options include immune checkpoint inhibitors such as pembrolizumab and cemiplimab, which activate the body's own immune system to fight the tumor. In cutaneous SCC with overexpression of the EGFR receptor, EGFR inhibitors such as cetuximab may be considered.

Photodynamic Therapy and Topical Treatments

For superficial lesions or precancerous changes such as actinic keratoses, photodynamic therapy, cryotherapy, or topical agents like imiquimod or 5-fluorouracil cream may be appropriate.

Prognosis

When detected at an early stage, the prognosis for squamous cell carcinoma is generally favorable, and most tumors can be completely removed. In advanced cases with lymph node involvement or distant metastases, the prognosis worsens significantly. Regular follow-up examinations are essential to detect recurrence early.

Prevention

• Consistent protection from UV radiation (sunscreen, protective clothing, avoidance of tanning beds)
• Abstaining from tobacco use
• HPV vaccination to prevent HPV-associated carcinomas
• Regular skin cancer screenings, especially for high-risk individuals
• Treatment of precancerous lesions such as actinic keratoses

References

1. German Guideline Program in Oncology: S3 Guideline on Squamous Cell Carcinoma of the Skin. AWMF Registration No. 032-042OL, 2020.
2. World Health Organization (WHO): Global Cancer Observatory (GLOBOCAN) 2020. International Agency for Research on Cancer. Lyon, 2020.
3. Bray F et al.: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 2024.