Saturday, January 10, 2026

Squamous Cell Carcinoma: Epidemiology, Causes, Pathophysiology, Symptoms, Diagnosis, Treatment, Prognosis and Prevention

Squamous Cell Carcinoma

~Introduction


Squamous Cell Carcinoma (SCC) is one of the most common forms of cancer worldwide, arising from squamous cells—flat, thin cells that make up the outermost layer of the skin (epidermis) and line various organs such as the lungs, esophagus, cervix, mouth, throat, and anus. SCC can occur in many parts of the body, but it is most frequently associated with the skin, where it ranks as the second most common type of skin cancer, following basal cell carcinoma.

Although SCC is often treatable when detected early, it can become aggressive, invade surrounding tissues, and metastasize to lymph nodes or distant organs if left untreated. This article provides an in-depth discussion of squamous cell carcinoma, including its causes, pathophysiology, clinical presentation, diagnosis, treatment options, prognosis, and prevention.

~Understanding Squamous Cells

Squamous cells are specialized epithelial cells designed to protect underlying tissues from physical injury, pathogens, and environmental exposure. These cells are constantly renewed through controlled cell division. When genetic mutations disrupt normal growth regulation, squamous cells may begin to multiply uncontrollably, leading to squamous cell carcinoma.

SCC can develop in:

  • Skin (cutaneous SCC)

  • Oral cavity

  • Oropharynx and larynx

  • Esophagus

  • Lungs

  • Cervix

  • Anus

  • Penis and vulva

Each site has unique risk factors and clinical behavior, but the fundamental cancer biology remains similar.

~Epidemiology

Squamous cell carcinoma accounts for millions of new cases globally each year.

  • Skin SCC: Second most common skin cancer

  • Lung SCC: Accounts for 20–30% of non-small cell lung cancers

  • Head and neck SCC: Represents over 90% of cancers in this region

  • More common in older adults, particularly over age 50

  • Higher incidence in men than women

  • Increased prevalence in individuals with light skin, immunosuppression, or chronic sun exposure

The incidence of SCC continues to rise worldwide due to increased UV exposure, aging populations, tobacco use, and HPV infections.

~Causes and Risk Factors

1. Ultraviolet (UV) Radiation

Chronic exposure to ultraviolet radiation from sunlight or tanning beds is the leading cause of cutaneous squamous cell carcinoma. UV radiation damages DNA, leading to mutations in tumor suppressor genes such as TP53.

2. Tobacco and Alcohol Use

Smoking and excessive alcohol consumption significantly increase the risk of SCC of the lungs, oral cavity, throat, and esophagus. Tobacco smoke contains carcinogens that directly damage epithelial cells.

3. Human Papillomavirus (HPV)

High-risk HPV strains, particularly HPV-16 and HPV-18, are strongly associated with SCC of the cervix, anus, and oropharynx.

4. Immunosuppression

Organ transplant recipients, HIV-positive individuals, and patients on long-term immunosuppressive therapy have a significantly increased risk of aggressive SCC.

5. Chronic Inflammation and Injury

Long-standing wounds, scars, burns, and inflammatory skin conditions can predispose to SCC, a phenomenon known as Marjolin’s ulcer.

6. Genetic Disorders

Certain inherited conditions increase SCC risk, including:

  • Xeroderma pigmentosum

  • Albinism

  • Epidermodysplasia verruciformis

~Pathophysiology

Squamous cell carcinoma develops through a multistep process involving genetic and molecular changes:

  1. DNA damage caused by carcinogens (UV light, tobacco)

  2. Failure of DNA repair mechanisms

  3. Mutation of tumor suppressor genes

  4. Uncontrolled cellular proliferation

  5. Invasion of surrounding tissues

  6. Potential metastasis via lymphatic or hematogenous spread

Precursor lesions such as actinic keratosis (on the skin) or squamous dysplasia (in mucosal surfaces) often precede invasive carcinoma.

~Clinical Features

Cutaneous Squamous Cell Carcinoma

Commonly appears on sun-exposed areas such as the face, ears, scalp, neck, hands, and arms.

Typical features include:

  • Firm, red nodule

  • Scaly or crusted plaque

  • Non-healing ulcer

  • Lesion that bleeds easily

  • Rapid growth over weeks to months

Oral and Oropharyngeal SCC

  • Persistent mouth sores

  • White or red patches (leukoplakia or erythroplakia)

  • Difficulty swallowing

  • Hoarseness

  • Unexplained weight loss

Lung SCC

  • Chronic cough

  • Hemoptysis (coughing blood)

  • Chest pain

  • Shortness of breath

  • Recurrent infections

Cervical SCC

  • Abnormal vaginal bleeding

  • Pelvic pain

  • Pain during intercourse

  • Vaginal discharge

~Diagnosis

Clinical Examination

Initial assessment involves inspection and palpation of lesions and regional lymph nodes.

Biopsy

Definitive diagnosis requires histopathological examination:

  • Shave biopsy

  • Punch biopsy

  • Excisional biopsy

Microscopic findings typically include:

  • Keratin pearls

  • Intercellular bridges

  • Atypical squamous cells

Imaging Studies

Used to assess tumor extent and metastasis:

  • CT scan

  • MRI

  • PET scan

  • Chest X-ray

Staging

SCC is staged using the TNM system:

  • T: Tumor size and invasion

  • N: Lymph node involvement

  • M: Distant metastasis

~Treatment Options

Treatment depends on tumor location, size, stage, and patient factors.

1. Surgical Management

  • Wide local excision

  • Mohs micrographic surgery (especially for facial or high-risk skin SCC)

  • Lymph node dissection if metastasis is present

2. Radiation Therapy

Used as:

  • Primary treatment when surgery is not feasible

  • Adjuvant therapy after surgery

  • Palliative treatment for advanced disease

3. Chemotherapy

Systemic chemotherapy is used for advanced or metastatic SCC.
Common agents include:

  • Cisplatin

  • Carboplatin

  • 5-Fluorouracil

4. Targeted Therapy

  • EGFR inhibitors (e.g., cetuximab)

  • Useful in head and neck SCC

5. Immunotherapy

Checkpoint inhibitors such as:

  • Pembrolizumab

  • Cemiplimab
    Have shown significant success in advanced cutaneous SCC.

~Prognosis

The prognosis of squamous cell carcinoma varies widely:

  • Early-stage skin SCC: Cure rates exceed 90%

  • Advanced SCC: Increased risk of recurrence and metastasis

  • Poor prognostic factors include:

    • Tumor size >2 cm

    • Deep invasion

    • Perineural invasion

    • Immunosuppression

    • Lymph node involvement

Five-year survival rates decrease significantly in metastatic disease but continue to improve with modern therapies.

~Complications

  • Local tissue destruction

  • Cosmetic disfigurement

  • Functional impairment (speech, swallowing, breathing)

  • Lymph node metastasis

  • Distant organ spread (lungs, liver, bones)

  • Psychological impact and reduced quality of life

~Prevention

Sun Protection

  • Use broad-spectrum sunscreen (SPF ≥30)

  • Wear protective clothing and hats

  • Avoid peak sun hours

  • Avoid tanning beds

Lifestyle Modifications

  • Quit smoking

  • Limit alcohol consumption

  • Maintain a healthy diet

HPV Vaccination

Highly effective in preventing HPV-related SCC of the cervix, anus, and oropharynx.

Regular Screening

  • Skin examinations

  • Oral cancer screenings

  • Cervical Pap smears

Early detection significantly improves outcomes.

~Living With Squamous Cell Carcinoma

Patients diagnosed with SCC often require long-term follow-up due to the risk of recurrence or new primary tumors. Emotional support, rehabilitation, and patient education play vital roles in comprehensive cancer care.

~Conclusion

Squamous cell carcinoma is a common yet potentially serious malignancy arising from squamous epithelial cells. While many forms of SCC are highly treatable when diagnosed early, delayed detection can lead to aggressive disease and significant morbidity. Advances in surgery, radiation, chemotherapy, targeted therapy, and immunotherapy have markedly improved patient outcomes. Public awareness, preventive strategies, and regular screening remain essential tools in reducing the global burden of squamous cell carcinoma.


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