Squamous cell carcinomas

ALSO KNOWN AS: Skin cancer, SCC

Related condition:Basal cell carcinomas

DEFINITION: Squamous cell carcinomas are malignant tumors that begin in the squamous cells forming the skin's outer layer, or epidermis.

Risk factors: Risk factors for squamous cell carcinomas include exposure to sunlight and ultraviolet radiation, age above fifty years, male gender, light-colored skin that burns easily, blue or green eyes, blond or red hair, residence in a geographical area that receives high sun exposure, repeated use of tanning beds, exposure to chemical carcinogens such as arsenic and tar, history of a large number of X-rays, history of prior nonmelanoma skin cancer, and chronic immunosuppression. Additionally, individuals with the hereditary disease xeroderma pigmentosum and those with human papillomavirus infection (HPV).

Etiology and the disease process: Cumulative lifetime sun exposure is the leading cause of squamous cell carcinoma. The shorter-wavelength portion of the ultraviolet spectrum (known as UVB) is about one thousand-fold more active in inducing skin cancer than the longer-wavelength portion, known as UVA. Squamous cell carcinoma spreads faster than basal cell carcinoma (skin cancer originating from basal keratinocytes in the epidermis) but may still be relatively slow-growing. A subset of high-risk squamous cell carcinoma is capable of infiltrating the local area and metastasizing to regional lymph nodes as well as to distant locations and internal organs, most often to the lungs. This subset accounts for most of the morbidity and mortality associated with squamous cell carcinoma. The overall risk of metastasis for squamous cell carcinoma is about 5 percent, though factors such as tumor size, recurrence, and differentiation give some lesions a higher risk.

Incidence: The annual incidence of squamous cell carcinoma in the United States is estimated to be around 1.8 million new cases yearly. Because health registries often exclude squamous cell carcinoma from their databases and the rate of this cancer varies based on geographical location, this number is complex to determine accurately.

Squamous cell carcinoma is the second most common form of skin cancer after basal cell carcinoma in whites. In people of African and Asian descent, squamous cell carcinoma, although relatively rare, is the most common form of skin cancer. Squamous cell carcinoma carries a higher mortality rate in blacks than in whites, probably because of delayed diagnosis, and occurs at a two to three times higher frequency in men than in women, presumably because of a higher cumulative exposure to sunlight.

There has been an apparent dramatic increase in the incidence of squamous cell carcinoma beginning in the 1990s in the United States. Scientists attribute this to increased sun exposure in the general population, the advancing age of the population, and earlier diagnosis because of increased public awareness of skin cancer.

Symptoms: Squamous cell carcinoma may manifest as a variety of primary morphologies. The main symptom is a growing bump with a rough, scaly surface and flat, reddish patches. A sore that does not heal can be a sign of squamous cell carcinoma. Squamous cell carcinomas typically occur on portions of the skin exposed to sunlight over several years. Most lesions appear on the head and neck, especially the face, arms, and hands. Histologically, a squamous cell carcinoma lesion involves the full thickness of the epidermis but without involvement of the dermis, the deep vascular inner layer of the skin.

Screening and diagnosis: Screening for squamous cell carcinoma involves regular skin examinations for new lesions or changes in an existing lesion. Suspicious changes in an existing lesion include a change in appearance, color, size, or texture; pain; inflammation; bleeding; or itching. An asymmetrical lesion that has irregular or diffuse borders, multiple colors, or is larger than six millimeters (mm) in diameter should be examined by a doctor.

The appearance of a skin lesion may indicate a squamous cell carcinoma, but a skin biopsy is required for a definitive diagnosis. The common types of biopsy are shave, punch, incisional, and excisional biopsy (removing only a portion of the suspicious tissue) and excisional biopsy (removing the entire suspicious region). A biopsy for squamous cell carcinoma is normally done in the doctor’s office after the patient is given a local anesthetic. Biopsy samples must be deep enough to reach the mid-dermis to determine the presence or absence of invasive disease. For high-risk lesions, a larger tissue sample may be taken to assess the extent of invasion into nerves and look for other features that indicate a greater risk of metastasis.

Squamous cell carcinoma is staged according to the TNM staging (tumor/lymph node/metastasis) classification system. Because most squamous cell carcinomas are not metastatic at the time of diagnosis, the stage (T1-T4) is based on the size and characteristics of the lesion.

Treatment and therapy: Most squamous cell carcinomas are treated in the doctor’s office by cryotherapy (cryosurgery), electrodesiccation and curettage, excision with conventional margins, or Mohs micrographic surgery. It is important to remove the lesion completely in the first treatment because it can recur, metastasize, and cause death. More advanced or more invasive squamous cell carcinomas may require more aggressive treatment, including surgical management, radiation therapy, or both.

Cryotherapy with liquid nitrogen is a safe and low-cost procedure. Electrodesiccation and curettage, which may be used to treat squamous cell carcinoma on the trunk and extremities, is a simple procedure involving scraping and burning the tissue in the lesion. Its effectiveness depends on the technique; cure rates improve with a doctor’s experience. Excision with conventional margins (4 mm for lower-risk lesions is recommended) is highly effective for many squamous cell carcinomas. This technique commonly involves the removal of a greater amount of normal tissue than is necessary for complete tumor removal. Mohs surgery, performed by dermatologic surgeons, allows for examining the entire surgical margin during the procedure and removing the tumor in a step-wise procedure until clear margins are obtained. Mohs surgery is routinely performed as an outpatient procedure with the patient under local anesthesia and is widely available in the United States.

Nonsurgical treatment options for squamous cell carcinoma include topical chemotherapy and immune response modifiers (generally used for premalignant lesions), photodynamic therapy, radiation therapy (generally used in patients for whom surgery is not feasible and as adjuvant therapy for patients with metastatic or high-risk squamous cell carcinoma), and systemic chemotherapy (for patients with metastatic disease).

Prognosis, prevention, and outcomes: Localized squamous cell carcinoma of the skin has a high cure rate if treated early. The overall five-year survival rate is estimated to be over 90 percent. For patients with no high-risk factors, this rate approaches 100 percent, and for patients with at least one high-risk factor, it decreases to around 70 percent. Risk factors associated with higher rates of recurrence and metastasis include tumors on the lips or ears; tumor size greater than two centimeters; an invasive, poorly differentiated, or recurrent tumor; nerve involvement; being an organ transplant recipient; having received chronic immunosuppressive therapy; and being infected with the human immunodeficiency virus (HIV) or having (AIDS).

Patients who develop one squamous cell carcinoma have a 40 percent risk of developing additional squamous cell carcinomas within the next two years and, therefore, should receive a complete skin examination every six to twelve months. Patients with high-risk tumors should receive complete skin and lymph node examinations every three to six months for at least two years.

The most important preventive measure is limiting exposure to sunlight. Skin should be protected by protective clothing such as hats, long-sleeved shirts, long skirts, or pants. A high-quality, broad-spectrum sunscreen that blocks UVA and UVB light should be applied at least thirty minutes before going outside and reapplied frequently. Exposure to sunlight at midday, when the sun is most intense, should be limited.

Bibliography

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Hanna, Glenn J., et al. "Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma." Clinical Cancer Research, 2024. doi.org/10.1158/1078-0432.CCR-24-0590.

Johnson, Daniel E., et al. "Head and Neck Squamous Cell Carcinoma." Nature reviews Disease Primers, vol. 6, no. 1, 2020, p. 92. doi.org/10.1038/s41572-020-00224-3.

National Comprehensive Cancer Network (U.S.). Squamous Cell Skin Cancer: Nccn Guidelines for Patients. INational Comprehensive Cancer Network, 2023.

Rabin, Matthew. Oral Squamous Cell Carcinoma: From Diagnosis to Treatment. Nova Science, 2021. 

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"Squamous Cell Carcinoma of the Skin." Mayo Clinic, 11 Aug. 2023, www.mayoclinic.org/diseases-conditions/squamous-cell-carcinoma/symptoms-causes/syc-20352480. Accessed 20 July 2024.

"Squamous Cell Carcinoma." Skin Cancer Foundation, Mar. 2023, www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma. Accessed 20 July 2024.