Squamous cell carcinoma of the skin is a common form of skin cancer that develops when certain cells in the top layer of skin begin to grow out of control. While this type of cancer can be serious if left untreated, most cases can be successfully removed when caught early, giving patients a good chance at full recovery.
Epidemiology
Squamous cell carcinoma, often called SCC, stands as the second most common type of skin cancer after basal cell carcinoma. In the United States alone, more than one million people receive a diagnosis of squamous cell carcinoma every year. This represents a significant public health concern, as the rate of SCC has climbed approximately 200 percent over the past three decades.[1]
The disease does not affect everyone equally. Men are about twice as likely to develop squamous cell carcinoma compared to women. Age plays a crucial role in risk, with people over 50 years old being the most likely to develop the condition. However, healthcare providers have noticed a concerning trend: the incidence of squamous cell carcinoma has been rising among people younger than 50 years of age.[1]
Mortality rates for cutaneous squamous cell carcinoma are comparable to those seen with melanoma, kidney cancer, and throat cancer in the central and southern regions of the United States. In Australia, where sun exposure is particularly intense, people die from squamous cell carcinoma every year despite the cancer’s generally treatable nature.[3][4]
Certain populations face higher risks. People with pale skin tones, blue or green eyes, and blonde or red hair are more vulnerable to developing this form of skin cancer. Individuals who are 65 years of age or older represent another high-risk group. The disease can develop anywhere on the body but most commonly appears on sun-exposed areas such as the face, ears, neck, scalp (especially in those who are bald or have thinning hair), forearms, backs of hands, and lower legs.[1][3]
Causes
The root cause of squamous cell carcinoma lies in damage to a specific gene called the p53 gene. This gene acts as a tumor suppressor, which means it normally controls how often and how much cells divide and replicate to replace old cells that have reached the end of their lifespan. When the p53 gene becomes damaged or mutated, it can no longer properly regulate cell growth, leading to the uncontrolled multiplication of squamous cells, which are flat cells located near the surface of the top layer of skin called the epidermis.[1][2]
The most common way that the p53 gene becomes mutated is through exposure to ultraviolet (UV) radiation from the sun or indoor tanning beds. When UV rays penetrate the skin, they damage the DNA inside skin cells. Over time, repeated exposure to UV radiation causes cumulative damage that can overwhelm the body’s natural repair mechanisms. This DNA damage from UV exposure is the primary driver behind most cases of squamous cell carcinoma.[1][3]
The danger of UV radiation exists even on cloudy days, as certain types of UV light can penetrate fog and clouds. Water, sand, concrete, and snow can reflect the sun’s rays, increasing exposure. UV rays can even reach below the water’s surface, meaning swimmers are not protected from radiation simply by being in the water.[21]
Risk Factors
While UV exposure represents the primary risk factor, several other conditions and circumstances can increase a person’s likelihood of developing squamous cell carcinoma. People with long-term sun exposure or significant sun damage to their skin at a young age face elevated risk. Those who work outdoors for extended periods accumulate more UV damage over time.[1][3]
Having a weakened immune system dramatically increases the risk of developing squamous cell carcinoma. This includes people who have received organ transplants and must take immunosuppressant medications to prevent organ rejection. When the immune system is compromised, it becomes less effective at identifying and destroying abnormal cells before they can develop into cancer.[1]
Certain skin conditions serve as warning signs for potential cancer development. Actinic keratoses, which are early skin changes that appear as rough, scaly patches, can transform into squamous cell carcinoma if not treated. People with sunspots or solar keratoses should be particularly vigilant about skin monitoring.[3]
Previous exposure to chemicals poses another risk factor. People who have been exposed to cigarettes, arsenic, or other toxic materials face higher chances of developing the disease. Chronic, non-healing wounds or old burn injuries can also become sites where squamous cell carcinoma develops. Individuals who received radiation therapy in the past may develop skin cancer in the treated areas years later.[1]
Infection with certain subtypes of human papilloma virus (HPV) has been linked to the development of squamous cell carcinoma. Specifically, HPV types 6, 11, 16, and 18 have been associated with this cancer, especially in patients whose immune systems are already compromised. A personal or family history of skin cancer also increases risk, as does having had precancerous skin lesions in the past.[3]
Symptoms
Recognizing the symptoms of squamous cell carcinoma early can make a significant difference in treatment outcomes. The first sign often appears as a thick, scaly area on the skin that refuses to heal. This abnormal patch may feel rough or dry to the touch and can be itchy or uncomfortable. The affected area might develop a crust that looks like a scab and may bleed from time to time.[1][3]
Squamous cell carcinoma can take various forms, which makes it important to be aware of different possible appearances. Some growths appear as raised bumps that stand higher than the surrounding skin but have a depression or sunken area in the middle. Others may look like wart-like growths with rough, thickened surfaces. Some lesions present as open sores that will not heal, or sores that seem to heal but then come back repeatedly.[1][2]
The cancer may also manifest as flat, scaly, red patches on the skin, often larger than about one inch or 2.5 centimeters across. These patches can have different colors from the surrounding skin. In some cases, squamous cell carcinoma appears as firm bumps with rough surfaces. The growths may crust over, itch, or bleed at times.[1][2]
Certain specific types of lesions can signal the presence or potential development of squamous cell carcinoma. A bump or lump that feels dry, itchy, or scaly and has a different color from surrounding skin might be an actinic keratosis, a precancerous lesion. A condition called cheilitis can develop on the lower lip, where the tissue becomes pale, dry, and cracked, often with a burning sensation when exposed to sunlight. White or pale spots in the mouth, on the tongue, gums, or cheeks, known as leukoplakia, can also be warning signs.[1]
When squamous cell carcinoma develops in the genital area, it may look like a small sore that does not go away. As the cancer grows deeper into the skin layers, it may begin to grow faster and can become painful. This change in growth rate or the development of pain signals that the cancer is progressing and requires immediate medical attention.[3]
Prevention
Because the vast majority of squamous cell carcinomas are linked to sun exposure, prevention strategies focus heavily on protecting the skin from ultraviolet radiation. The most effective prevention involves a combination of sun avoidance, protective clothing, and proper sunscreen use. These measures work together to reduce the cumulative UV damage that can lead to cancer decades later.[19]
Limiting direct sun exposure during peak hours represents one of the most important preventive steps. The sun’s rays are strongest between 10 a.m. and 3 p.m., so avoiding outdoor activities during this window reduces risk. When spending time outside is necessary during these hours, seeking shade whenever possible provides additional protection. Trees, awnings, umbrellas, and other forms of shade can significantly reduce UV exposure.[19][21]
Wearing appropriate clothing creates a physical barrier against UV radiation. Long-sleeve shirts, long pants, and wide-brimmed hats that shade the face and neck offer excellent protection. For maximum effectiveness, choose clothing made from tightly woven fabrics in darker colors, as these generally provide more protection than light-colored, loosely woven materials. Some clothing is specifically designed with a UV protection factor (UPF) label, indicating how much UV radiation the fabric blocks. Sunglasses that provide 100 percent UV protection help shield the delicate skin around the eyes from damage.[19][22]
Sunscreen serves as an essential tool for protecting exposed skin that cannot be covered by clothing. Choose a broad-spectrum sunscreen with a sun protection factor (SPF) of at least 30 that protects against both UVA and UVB rays. Look for ingredients like Parsol 1789 (also known as avobenzone) or titanium dioxide on the label, as these provide comprehensive protection. Water-resistant formulas are preferable because they are more likely to remain effective even when swimming or sweating.[19][21]
Proper sunscreen application makes a significant difference in effectiveness. Apply sunscreen generously to all exposed skin, using approximately one ounce to cover the entire body for adults. Reapply at least every two hours when outdoors, and more frequently after swimming or heavy perspiration. Do not forget often-missed areas like the ears, back of the neck, tops of feet, and backs of hands. Lip balm with SPF 15 or higher protects the lips, which are particularly vulnerable to sun damage.[19]
Avoiding indoor tanning beds and their UV light is crucial for prevention. Tanning beds emit concentrated UV radiation that can cause premature skin aging and significantly increase skin cancer risk. No amount of indoor tanning is considered safe, regardless of the device or facility used.[19]
Regular skin self-examinations help with early detection of potentially cancerous changes. Check your entire body regularly, looking for any new growths, changes in existing moles or spots, or areas that look different from the surrounding skin. Pay attention to changes in shape, color, or size of any marks on your skin. If you notice anything unusual or suspicious, schedule an appointment with a dermatologist promptly. People who have previously had skin cancer or who have multiple risk factors should see a dermatologist for a full-body examination at least once a year.[3][15]
For individuals who must be outdoors for extended periods due to work or other commitments, taking extra precautions becomes even more important. Schedule breaks in shaded areas when possible, reapply sunscreen frequently, and wear protective clothing consistently. Those taking antibiotics or certain other medications should ask their doctor or nurse whether the medication might increase skin sensitivity to sunlight, as this would require additional protective measures.[21]
Pathophysiology
Understanding how squamous cell carcinoma develops requires knowledge of normal skin structure and function. The epidermis, the outermost layer of skin, contains three main types of cells. Squamous cells are flat cells located near the skin’s surface that continuously shed as new cells form beneath them. Under normal circumstances, these cells follow an orderly process of growth, maturation, and replacement governed by genetic instructions.[2]
When DNA damage from UV radiation or other sources affects the p53 gene, the normal control mechanisms that regulate cell division begin to fail. The p53 gene normally acts as a checkpoint, preventing damaged cells from dividing and giving the body time to repair DNA damage or eliminate cells that cannot be repaired. When this gene becomes mutated, it can no longer perform its protective function effectively.[1]
Without proper regulation from the p53 gene, squamous cells begin to multiply in an abnormal and accelerated manner. Instead of following the usual pattern of controlled growth and replacement, these cells divide rapidly and accumulate, forming abnormal growths. The damaged cells no longer respond appropriately to signals that would normally tell them to stop dividing or to die when they become old or damaged.[1][2]
Initially, these abnormal changes may remain confined to the very top layer of the epidermis, a stage called in situ cancer. At this early stage, the cancer has not yet penetrated into deeper skin layers. An example is Bowen’s disease, which is an early stage squamous cell carcinoma localized to the outermost skin layer. Precancerous conditions like actinic keratoses represent even earlier changes that may eventually transform into full squamous cell carcinoma if left untreated.[2][3]
As the cancer progresses, it becomes invasive, meaning the cancerous cells have spread into the deeper layers of the skin beyond the epidermis. The growth tends to be slow initially, but as it extends into deeper tissues, the cancer may begin to grow faster. At this stage, the tumor can become painful and more aggressive in its behavior.[3]
If squamous cell carcinoma continues growing without treatment, it can potentially become metastatic, meaning the cancer spreads to other parts of the body beyond the original skin location. While this is relatively rare, when it does occur, the cancer most commonly spreads first to nearby lymph nodes. Lymph nodes are small bean-shaped structures that are part of the immune system. From the lymph nodes, the cancer can potentially spread to distant tissues and organs. Metastatic squamous cell carcinoma is more difficult to treat and carries a more serious prognosis.[1][3]
The physical and biochemical changes in squamous cell carcinoma involve alterations in cell adhesion, meaning cancerous cells become less attached to their neighbors. This allows them to break away and potentially invade surrounding tissues. The cells also develop the ability to stimulate new blood vessel formation, a process called angiogenesis, which provides the growing tumor with nutrients and oxygen. These changes represent fundamental shifts in how the cells function compared to normal, healthy squamous cells.[4]
