Squamous cell carcinoma (SCC) is a skin cancer that arises from the uncontrolled growth of squamous cells in the epidermis, the outer layer of skin.
Sometimes this skin tumor is referred to as cutaneous squamous cell carcinoma (CSCC). This distinguishes it from squamous cell carcinomas that occur in other parts of the body.
Squamous cell carcinoma is the second most common skin cancer
Squamous cell carcinoma is the second most common type of skin cancer. Only basal cell carcinoma is more common. It accounts for about 20% of all skin cancers.
In the United States, it is estimated that over 700,000 new cases of cutaneous squamous cell carcinomas are diagnosed. Because CSSCs are excluded from national registries, the exact incidence, along with the exact number of deaths from this skin cancer is unknown.
Like basal cell carcinoma, SCCs are caused by long term exposure to ultraviolet radiation from sun exposure and indoor tanning devices.
Although SCCs may occur anywhere on the body, they most frequently develop in areas that have been exposed to the sun. These include:
- balding scalp
- back of the hands
The appearance of squamous cell carcinomas can vary
Squamous cell carcinomas often appear as a thick, rough, scaly patch that persists. It may occasionally bleed or develop a recurring crust.
SCC may appear like a wart with a rough surface or an inflamed scaly sore that does not heal.
The clinical course of squamous cell carcinoma
Although most patients who develop SCCs have localized disease that can be cured, tumor recurrence, tumor spread to other parts of the body, and death occasionally occurs.
Larger tumors may cause disfigurement as they may penetrate into the underlying tissues causing nerve or muscle damage. SCCs that have spread into the underlying tissue have been resistant to previous therapy or have reoccurred are considered “advanced” SCCs.
Risk factors for squamous cell carcinoma
The following are risk factors for squamous cell carcinoma:
- Fair-skinned individuals with blond or red hair, light-colored eyes (green, blue, or gray)
- A history of excessive exposure to UV radiation (sunlight or tanning beds)
- Older than 50 years of age
- Male gender
- History of basal cell carcinoma or other skin cancer
- Immunosuppression: including patients who have had an organ transplant, suffer from chronic leukemia, or those on immunosuppressive medication
- History of human papillomavirus infection 
- Psoriasis patients
Staging of squamous cell carcinoma
Staging of squamous cell carcinomas  is used to determine if, or how far, the cancer has spread. Treatment plans are determined by the stage or extent of the disease.
Factors that determine the stage of an SCC include:
- the size of the tumor
- the depth of growth into the skin
- whether the tumor has spread to lymph nodes or other parts of the body
Cancer staging helps determine treatment plans and provides information about survival.
Squamous cell carcinoma staging is based on the American Joint Committee on Cancer (AJCC) TNM system. 
T – Primary Tumor: Determined by tumor size and thickness, high-risk features, and level of invasion.
N – Regional Lymph Nodes: Based on the location and number of lymph nodes with cancer cells, and the size of the metastatic tumor.
M – Metastasis: Whether the tumor has spread to other parts of the body.
Once the detailed TNM stage is obtained, a simpler five-level stage is determined. The lower the stage, the better the prognosis.
The original tumor is limited to the most superficial layer of skin, the epidermis. This stage is also called squamous cell carcinoma in situ.
The tumor is less than or equal to 2 centimeters in width. Although it may have spread into the second layer of skin the dermis, it has not invaded underlying muscle, cartilage or bone. In addition, the tumor has not spread to lymph nodes or other parts of the body. No more than two high-risk features apply. (See below)
The tumor is larger than 2 centimeters and may have extended into the dermis. The tumor has not spread to the underlying muscle, cartilage, or bone, to lymph nodes, or to other parts of the body.
The cancer has spread to areas below the skin. It has invaded the muscle, bone, cartilage, or local lymph nodes but it has not spread to other parts of the body.
The cancer can be of any size. It has spread to areas outside of the skin including distant organs like the brain or lungs. It may also have spread to local lymph nodes.
High-risk features of squamous cell carcinoma
High-risk features are characteristics of the tumor that increase the chances that the SCC reoccurs after initial treatment or spreads to other parts of the body.
- 2 mm thick or Clark level ≥ IV
- A tumor that grows around a nerve
- SCC located on the ear or lip
- Poorly or undifferentiated cells on pathology (Differentiation refers to how similar the cancer cells look like the normal tissue from which the cells are derived. Poorly and undifferentiated cells spread more quickly.)
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Treatment of squamous cell carcinoma
Fortunately, most squamous cell carcinomas of the skin are found in their earlier stages where they can be cured utilizing local treatment methods, such as:
Electrodesiccation and curettage
The abnormal tissue is scraped off the skin with a curette, a sharp round-tipped blade on a handle. The area is heated with an electrode that stops the bleeding and destroys the abnormal cancer cells that remain on the edge of the wound. This procedure is repeated several times. It is the ideal treatment for small low-risk superficial SCCs especially those found on the trunk and extremities.
The cancer and underlying tissue, along with a margin of normal skin to assure complete removal, is excised with a scalpel. The specimen is sent for pathological evaluation to confirm that the cancer is completely removed. This treatment is ideal for SCCs found in areas of the body where tissue sparing is not critical.
Mohs Micrographic Surgery
Mohs surgery involves the removal of skin cancer tissue, layer by layer, examining each layer at the time of excision until no evidence of tumor exists. Although it is complicated and time-consuming, the procedure has the highest cure rates of all therapies for SCC.
It is best utilized for high-risk tumors, large or aggressive cancers, recurrent tumors, and cancers that occur in cosmetically sensitive areas around the eyes, nose, lips, ears, fingers, or genitals.
Radiation therapy is often used in addition to surgery for tumors that have perineural invasion (cancer cells surround or track along a nerve) or regional metastasis. This type of therapy may be used as a primary treatment for SCC when surgery is not an option.
Multiple anticancer drugs are used to shrink or kill cancerous cells and reduce the spread of SCC tumors.
Multiple topical skin products are available for precancerous lesions and early in situ SCCs:
- 5-fluorouracil is a topical antimetabolite anticancer drug that is approved for pre-cancerous skin lesions but is often utilized to treat small early cutaneous SCCs cancers.
- Imiquimod is approved by the FDA to treat genital warts, precancerous lesions. and superficial basal cell carcinoma. It is often used on early SCCs.
- Vitamin A derivatives (retinoids) have been used to both treat and prevent non-aggressive SCC.
Treatment of advanced squamous cell carcinoma
Advanced SCCs can become life-threatening. In rare cases, when the SCC has spread to local lymph nodes and to more distant organs of the body, treatment often involves surgery, radiation therapy, and/or chemotherapy.
For patients with advanced disease who are not eligible for more standard treatments, inhibitor immunotherapy is an option. The FDA has approved an intravenous infusion drug, Cemiplimab. Cemiplimab is for patients with locally advanced SCC of the skin, metastatic cutaneous squamous cell carcinoma, or for patients where surgery or radiation is not an option. Pembrolizumab  is also an effective and well-tolerated immunotherapy option for patients with advanced disease.
Anti-cancer chemotherapy agents such as cisplatin (a platinum coordination compound that disrupts DNA synthesis), doxorubicin, and 5-fluorouracil may be used.
Prevention of squamous cell carcinoma
The American Academy of Dermatology makes the following recommendations to help reduce the chances of developing SCC:
- When possible, wear protective clothing (a long-sleeved shirt, pants, wide-brimmed hats, and sunglasses) to minimize direct sun exposure to the skin
- Seek shaded areas especially between 10 a.m. and 4 p.m. when the sun’s ultraviolet radiation is most intense
- Apply a broad-spectrum sunscreen with an SPF (sun protection factor) of 30 or higher on all exposed skin. The sunscreen should be applied liberally and reapplied every 2 hours or more if excessively sweating or swimming.
- Avoid tanning beds
- Perform regular self-skin exams and note any changing moles or other skin lesions.
- Seek medical attention should you discover a new or changing skin growth.
The bottom line
Squamous cell carcinomas can vary from small easily treated lesions that can have local therapy to, in rare instances, a serious life-threatening disease that may require surgery, radiation, and/or chemotherapy.
As is true for all skin cancers, prevention, avoidance of sun exposure, is the best medicine. You should routinely examine your skin and seek the opinion of a dermatologist should you find an unexplained or suspicious skin lesion.
Other articles about skin cancer by Fayne Frey, M.D.:
- Three Rare Skin Cancers You Should Know About
- What You Need to Know About Basal Cell Carcinoma
- Melanoma: What You Need to Know About Diagnosis and Treatment
Additonal information on skin cancer can be found at the Skin Cancer Foundation
 J AM Acad Dermatol 2013 Jun;68(6):957-66. doi: 10.1016/j.jaad.2012.11.037. Epub 2013 Feb 1. https://pubmed.ncbi.nlm.nih.gov/23375456/
 Jad Chahoud, MD1Adele Semaan, MPH2Yong Chen, PhD3; et al
Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals—A Meta-analysis https://jamanetwork.com/journals/jamadermatology/fullarticle/2478039
 Stages of Squamous Cell Carcinoma By Editorial Team https://skincancer.net/types-signs/squamous-cell-carcinoma-stages/May 16, 2017
 American Joint Committee on Cancer (AJCC) TNM system.
 ChemoCare – Cemiplimab-rwlc https://skincancer.net/types-signs/squamous-cell-carcinoma-stages/
 ChemoCare – Pembrolizumab httpss://chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx
Published 2/11/19. Updated by author 2/2/21
Fayne Frey, MD
Fayne Frey, M.D., is a board-certified clinical and surgical dermatologist practicing in West Nyack, New York, where she specializes in the diagnosis and treatment of skin cancer. She is a nationally recognized expert in the effectiveness and formulation of over-the-counter skincare products.
She is a frequent speaker in many venues where she captivates audiences with her wry observations regarding the skincare industry. She has consulted for numerous media outlets, including NBC, USA Today, and, the Huffington Post. and has also shared her expertise on both cable and major TV outlets.
Dr. Frey is the Founder of FryFace.com, an educational skincare information and product selection service website that clarifies and simplifies the overwhelming choice of effective, safe and affordable products encountered in the skincare aisles.
Dr. Frey is a graduate of the Weill Cornell Medical College and is a fellow of both the American Academy of Dermatology and the American Society for Dermatologic Surgery.
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