Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) refers to cancer of the squamous cells. Squamous cells are most commonly found in the epidermis, the outermost layer of the skin.  The epidermis is divided into layers called the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. Cutaneous squamous cell carcinoma is a cancer of the keratin producing cells in the squamous epithelium (i.e., keratinocytes) within the stratum spinosum layer of the epidermis. It may be visible as skin growths that appear as a non-healing, ulcerated (i.e. crusted) nodule or erosion in the skin. Most commonly, it is found on sun-exposed areas, such as the face, neck, and extremities. It is the second most common form of skin cancer, after basal cell carcinoma.

Squamous cell carcinoma can also be found in other organ systems that are made up of squamous cells. Other organs that may develop squamous cell carcinoma include the oral cavity (i.e., mouth), nasopharynx (i.e., area where the nasal passage and upper throat connect), oropharynx (i.e., area where mouth and throat connect), larynx (i.e., area in the throat containing voicebox), thyroid, esophagus, lungs, vagina, cervix, and penis.

Due to the wide variety of organs that squamous cell carcinoma can affect, it is one of the most common cancers that is capable of metastasizing within the U.S.

If caught early, cutaneous squamous cell skin cancer can be treatable. However, the seriousness of SCC depends on many factors such as size, location, metastasis, patient age, and other characteristics of the cancer cells.

Head and neck squamous cell cancers (e.g., oral cavity, nasopharynx, oropharynx, larynx, nasal cavity, and hypopharynx) account for around 90% of all head and neck cancers. If caught early, there is a 75% survival rate after five years. Unfortunately, because the symptoms are less apparent, most patients are diagnosed later in the disease course, which has a worse prognosis. 

For esophageal and lung cancer, the prognosis is also based on whether the cancer has metastasized. The overall five-year survival rate of esophageal squamous cell carcinoma is around 40%. Similarly, the overall five-year survival rate for all lung cancers is 14%. 

The introduction of regular papanicolaou smears (i.e., pap smear test) has drastically increased the amount of cervical cancers that are caught early. While early detection typically results in a more favorable prognosis, the overall five-year survival rate of cervical SCC is between 55-82%. 

It’s important to note that squamous cell carcinoma survival rates can vary depending on the study cited and may change with medical advances. 

The causes of squamous cell carcinoma (SCC) depend on which organ system is affected. Risk factors associated with cutaneous SCC include increased exposure to UV radiation through sunlight or tanning beds, increasing age, male sex, having lighter skin, ionizing radiation, and arsenic exposure. Chronic immunosuppression, such as after organ transplants or having HIV or leukemia, may also increase the risk of developing SCC. To lower the risk of developing cutaneous SCC, the American Cancer Society recommends using consistent sun protection, such as sunscreen, hats, and protective clothing if going out in the sun. 

SCC of the skin presents as a firm, painless, erythematous (i.e., red), ulcerated sore or nodule on the skin. The lesion may also easily bleed or feel scaly in texture. Although SCC can be found anywhere on the body, it is most commonly found on sun-exposed parts of the body, such as the scalp, lips, ears, and hands. Precancerous growths called actinic keratosis may also be present on the skin. Actinic keratosis appears as crusty, scaly, hyperkeratotic papules but can transform over time into SCC. Therefore, early detection of actinic keratosis and routine dermatologic screening can help to reduce the risk of developing SCC. Keratoacanthomas are another type of low-grade squamous cell carcinoma that presents as a volcanic, dome-shaped nodule. It appears rapidly and may spontaneously disappear without treatment.

For head and neck cancer, an individual or healthcare provider may observe ulcerations in the mouth or throat, bleeding, hoarseness, dysphagia (i.e., difficulty swallowing), difficulty breathing, or enlarged lymph nodes. With esophageal cancer, dysphagia and hoarseness may also be present alongside coughing or heartburn. An individual with thyroid cancer may feel a lump on their neck and may experience hoarseness and dysphagia. Lung cancer can present as a consistent cough that does not go away or hemoptysis (i.e., coughing up blood). In reproductive organs, such as the cervix, penis, or vagina, there may be discharge or abnormal bleeding, pain during intercourse, or pain during urination. 

With all types of cancer, fatigue and weight loss may also occur. 

Cutaneous SCC may first be visualized by a healthcare professional and diagnosis may be confirmed with skin biopsy. Many biopsy techniques may be employed, such as a punch biopsy (i.e., circular), wedge biopsy (i.e., V-shaped), shave biopsy (i.e., thin superficial), or excisional biopsy (i.e., surgical removal). The type of biopsy depends largely on the depth of invasion, width, area of skin, and other characteristics. Once the biopsy is obtained, a histological analysis will be performed. Typically, keratin pearls (i.e., concentric layers) and atypical keratinocytes may be seen under a microscope.

In comparison, other internal types of squamous cell carcinoma can be diagnosed primarily via imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound. Once a tumor has been identified, a biopsy may also be warranted. 

Cervical SCC may be diagnosed using a papanicolaou (pap) smear test, which biopsies cervical cells during a routine gynecological visit. 

Treatment for SCC will largely be based on the characteristics of the growth, such as depth of invasion, location, and width. Excision is the primary goal of treatment. In some cases, surgical excision can successfully remove the entire lesion, while in other cases, surgery may also be needed to remove any affected lymph nodes and prevent further metastasis. 

Specifically for cutaneous SCC, Mohs microsurgery, in which a dermatologist removes layer by layer of skin to assess for cancer cell invasion, may also be employed. Mohs surgery is particularly useful for SCC that arises on the face or genitals to reduce scarring and preserve healthy tissue. Cryotherapy or electrodessication and curettage can also be used to destroy premalignant growths or carcinoma in-situ.

In certain cases, radiation or chemotherapy may be necessary if the growth is considered high-risk (e.g., if the lesion is greater than 2mm, if there is indication of invasion, or if there is undifferentiated histology) or if there is metastasis present.