Squamous cell carcinoma (SCC) is thought to develop when skin cells accumulate mutations in their DNA and genetic code. “Keratinocytes make up the epidermal or very top layer of the skin,” explains Dr. Adam Mamelak, a board-certified dermatologist and skin cancer expert in Austin, Texas. When genes in these keratinocyte cells are mutated, such as TP53, a gene that suppress tumor growth, the mutated cells become immortal. “This means they don’t die and turn over like normal skin cells.” These cells continue to reproduce and replicate, acquiring more and more mutations, until they are eventually ‘transformed’ into skin cancer.
There are specific stimuli that can induce or facilitate these mutations in skin cells.
Ultraviolet (UV) radiation
UV light exposure is by far the most well recognized cause of mutation in skin cells. “UV light actually induces a very specific type of mutation in DNA,” says Dr. Mamelak. These ‘UV signature’ mutation are found in a majority skin cancers.
“This is why dermatologists make such a big deal about protecting the skin from excess sun exposure. We know that the sun damages the skin, and this type of damage is directly observed in skin cancer. High altitudes, living close to the equator, spending time in tanning salons or just a lot of outdoor activities. All these things increase UV exposure and therefore the chance of getting damage and mutations in our skin cells.”
Ionizing radiation and other carcinogens
Exposure to X-rays has been associated with the development of SCC. “Believe it or not, Grenz ray radiation treatments for acne once popular and considered extremely effective treatment for severe and scarring acne on the skin. Unfortunately, years later we began to see skin cancers developing in the irradiated areas.” Similarly, tumors have been seen in patients treated by an oncologist with radiation therapy for other internal malignancies in the body.
Chemical carcinogens can also predispose to the appearance of SCC. Substances like arsenic, that can be found in well water, have been shown to lead to the development of pre-cancerous keratosis on the skin.
Human papillomavirus infection
Human papillomavirus (HPV) is responsible for the development of warts on the skin. A few high-risk subtypes of HPV have been associated with SCC, especially when SCC develops in the throat and gential area. Although common warts can be seen with SCC, they are not considered a significant risk for the development of this cancer.
Chronic Inflammation & Scarring
A number of other infections have been associated with the development of SCC. In general, many of these infections cause exuberant inflammation in the skin and can also lead to scarring. In fact, SCC has been reported to develop in areas with deep fungal infections, severe and scarring acne lesions, and even within tuberculosis skin lesions. The mechanism behind the development of these tumors is unclear, however many believe it is the chronic inflammation initiated by the body to fight off these infections that actually leads to the growth of these tumors.
Some evidence for this comes from the observation that SCC can develop within chronic, non-healing wounds and ulcers. The term “Majorlin ulcer” typically refers to these skin cancers that develop in areas of chronic ulceration. SCC has also developed in burn scars and other potentially scarring skin lesions such as lichen planus, discoid lupus and epidermolysis bullosa (all associated with significant inflammation).
“Our immune systems act like surveillance systems, detecting infections in our bodies as well as cancer cells,” says Dr. Mamelak. “If the immune system is suppressed, cancer cells can go undetected and continue to grow and spread.” Increased rates of skin cancer are observed in patients with suppressed immune systems, such as those with HIV and leukemia. “The patients probably at greatest risk though are transplant patients, who take immune suppressing medications to ensure their transplant survives.” Dr. Mamelak notes that solid organ transplant recipients have a 65- to 250-times increased risk of developing SCC.
DNA Repair Failure
Our skin cells all possess an inherent mechanisms to repair themselves, especially DNA and genes that are damaged or mutated. There are some scenarios, such as a genetic disease called xeroderma pigmentosum, where the DNA repair mechanisms are impaired. These patients develop mutations in their skin cells at increased rates and hence are predisposed to skin cancers.