Causes and Risk Factors for Squamous Cell Carcinoma
Squamous cell carcinoma (SCC) is one of the most common forms of skin cancer, developing in the squamous cells found in the outer layer of the skin and in the lining of certain mucous membranes. Understanding what causes squamous cell carcinoma and which risk factors raise the odds of developing it supports earlier detection and more informed conversations with a clinician.
Key Takeaways
- Squamous cell carcinoma develops when squamous cells accumulate DNA damage, most often from years of cumulative ultraviolet (UV) exposure to the skin or mucous membranes.
- A weakened immune system, including long-term immunosuppressive therapy after an organ transplant, meaningfully raises squamous cell carcinoma risk.
- Infection with certain high-risk HPV types, especially HPV-16, is linked to squamous cell carcinoma of the oropharynx and several other mucosal sites.
- Cigarette smoking and drinking alcohol heavily both raise the odds of developing this cancer in the oropharynx and other head-and-neck locations.
- Chronic skin inflammation, long-standing wounds, and untreated actinic keratosis can also progress toward squamous cell carcinoma over time.
Main Causes and Risk Factors for Squamous Cell Carcinoma
Squamous cell carcinoma develops when squamous cells — found in the outer layer of the skin and lining parts of the mouth, throat, and other mucous membranes — build up genetic changes that disrupt their normal growth cycle. Most of this damage accumulates gradually from repeated external exposures, though a smaller share of cases involve changes in genes that normally help a cell repair DNA damage or stop dividing once that damage becomes too extensive.
The causes and risk factors for squamous cell carcinoma generally fall into a few overlapping groups: cumulative UV exposure, immune status, certain viral infections, occupational or chemical exposures, and behaviors such as tobacco and alcohol use. Carrying several of these factors together raises the overall chance of developing squamous cell carcinoma, though no single exposure guarantees the disease will occur, and cases sometimes arise without any identifiable risk factor.
Skin or mucosal inflammation that persists for long periods — including chronic wounds, burns, and long-standing scars — is also a recognized contributor. When tissue in these areas undergoes sustained irritation and repeated repair cycles over years, the chance of a cancerous change developing gradually increases.
| Risk Factor | Category |
|---|---|
| Cumulative UV exposure (sunlight or tanning devices) | Environmental |
| Weakened immune system, including after organ transplant | Medical |
| High-risk HPV infection (e.g., HPV-16) at mucosal sites | Biological / Infectious |
| Fair skin, light eyes, red or blond hair | Genetic / Biological |
| Tobacco use and heavy alcohol use | Lifestyle |
| Arsenic exposure or prior radiation treatment | Environmental / Occupational |
| Long-standing skin inflammation or actinic keratosis | Dermatological |
UV Exposure and Its Role in Squamous Cell Carcinoma Risk
Sunlight and indoor tanning equipment are the leading modifiable drivers of squamous cell carcinoma risk. UV rays damage DNA inside skin cells, including in the TP53 gene, which under normal conditions helps a damaged cell either repair itself or self-destruct before it can divide further. Somatic changes in TP53 are found in close to half of head and neck squamous cell carcinomas, underscoring how central this DNA-repair pathway is to the way the disease develops.
Cumulative, long-term UV exposure — the kind that builds up over years of outdoor work, recreation, or indoor tanning — plays a larger role in squamous cell carcinoma risk than any single sunburn episode, since UV-related DNA damage accrues in skin cells over time rather than resulting from one exposure alone.
A clinical study cited by the National Cancer Institute found that treating sun-damaged skin with topical fluorouracil lowered the chance that actinic keratoses — rough, scaly precancerous patches — progressed to squamous cell carcinoma requiring surgery, and the agency includes actinic keratosis itself among the recognized risk factors for nonmelanoma skin cancer.
Who Is Most at Risk for Developing Squamous Cell Carcinoma
Fair skin that burns or freckles easily, combined with light-colored eyes and red or blond hair, remains one of the most consistent personal risk factors, since lower melanin levels leave skin cells less protected from UV-related DNA damage. As with most cancers, the likelihood of developing squamous cell carcinoma also rises with age, reflecting decades of accumulated sun exposure.
A weakened immune system substantially raises squamous cell carcinoma risk. This includes solid organ transplant recipients, who take long-term immune-suppressing medication that limits the body’s ability to detect and clear abnormal cells before they turn cancerous. People with other causes of reduced immune function face a similar pattern of elevated risk.
The following groups face an elevated likelihood of developing squamous cell carcinoma:
- People with a personal or family history of squamous cell carcinoma, basal cell carcinoma, or actinic keratosis
- Organ transplant recipients on long-term immunosuppressive therapy
- Individuals with chronic, non-healing wounds, burns, or long-standing scars
- People with heavy cumulative UV exposure from outdoor occupations or frequent indoor tanning
- Those infected with high-risk HPV types, particularly for squamous cell carcinoma of the oropharynx or genital area
- Those who smoke or drink alcohol in heavy amounts, a combination that especially raises risk in the oral cavity and throat region
Additional Triggers That Increase Squamous Cell Carcinoma Risk
Infection with certain high-risk types of human papillomavirus, especially HPV-16, is a recognized risk factor for squamous cell carcinoma of the oropharynx — the middle part of the throat that includes the base of the tongue and the tonsils — and the number of oropharyngeal cancer cases linked to HPV has been rising. More broadly, the Centers for Disease Control and Prevention estimates that HPV infection causes about 36,000 cancers a year in the United States, across sites that include the oropharynx, cervix, vagina, vulva, penis, and anus.
Using tobacco in any form, including cigarettes and smokeless products, and drinking alcohol heavily both push up the odds of this cancer developing in the oropharynx, alongside HPV infection and a previous head-and-neck cancer diagnosis.
Exposure to arsenic, including through contaminated drinking water, and prior treatment with radiation are also established risk factors for nonmelanoma skin cancer, including squamous cell carcinoma.
Squamous cell carcinoma can also develop within skin that has been chronically inflamed, wounded, or scarred for long periods, a pattern the National Cancer Institute includes among nonmelanoma skin cancer risk factors. Because this type of squamous cell carcinoma forms gradually within tissue that already looks abnormal, it can take years before it is recognized as cancer rather than as a slow-healing injury.
Frequently Asked Questions
Can squamous cell carcinoma develop in people with darker skin tones?
Yes. Fair skin is a stronger risk factor because it offers less natural protection against UV damage, but squamous cell carcinoma can occur in people of any skin color. Anyone who notices a new, changing, or non-healing skin lesion should have it evaluated by a clinician regardless of skin tone.
Is squamous cell carcinoma hereditary?
A direct hereditary link is uncommon; most squamous cell carcinoma cases result from DNA changes that accumulate over a person’s lifetime rather than being inherited. A personal or family history of skin cancer is itself a recognized risk factor, and genetic predisposition typically interacts with UV and other exposures rather than acting as a standalone cause.
Does diet or nutrition influence squamous cell carcinoma risk?
Research directly linking specific diets to squamous cell carcinoma risk is still limited. Heavy alcohol consumption, however, is an established risk factor, particularly for squamous cell carcinoma of the head and neck. No specific diet has been proven to prevent squamous cell carcinoma, though overall healthy habits may support the body’s defenses alongside proven protective steps such as limiting UV exposure.
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