Squamous cell carcinoma (SCC)

Squamous cell carcinoma, also known as SCC or intraepithelial carcinoma, is a common skin cancer, especially frequent in fair-skinned older people. SCC usually grows on sun-exposed parts of the body without causing serious medical problems, but it can spread to other parts of the body in some cases.  If diagnosed early, squamous cell carcinoma is easily treated, but a small percentage of cases can be fatal.

Cause

99 per cent of squamous cell carcinomas are caused by ultraviolet (UV) radiation from sun exposure.1 UV radiation damages DNA in cells, so that they no longer grow correctly and skin cancer can develop.2 Squamous cell carcinoma is caused by cumulative long term sun exposure over many decades,3 including in adulthood and later life, meaning that people who work outside are at higher risk.4

In some cases, the human papilloma virus (HPV), which causes warts and cervical cancer, appears to act together with sun exposure to lead to development of SCC.5

Statistics

Statistics for squamous cell carcinoma show that the number of new cases in Australia doubled between 1985 and 2002. In 2002, approximately 80,000 cases of SCC were diagnosed.4 Squamous cell carcinoma is more common with increasing age, with the vast majority occurring in people aged 55 and above.5 Males are approximately one and a half times more likely to develop SCC than females.2

Each year in Australia, over 600 people die from SCC.6

Risk factors

Major risk factors for developing squamous cell carcinoma are:

• Previous squamous cell carcinoma or basal cell carcinoma: Up to 60 per cent of people with one of these non-melanoma skin cancers develop another in the next three years7
• Immunosuppression (i.e. a poor immune system). This is common in people taking certain medications, e.g. transplant recipients, people on chemotherapy or long-term steroids, or some medications for arthritis or inflammatory bowel disease. Medical conditions causing immunosuppression (e.g. AIDS) can also increase the risk of developing SCC or other skin cancers.
• Exposure to arsenic8
• Fair complexion, a tendency to burn rather than tan, the presence of freckles, light eye colour, light or red hair colour
• Age > 40 years
• Male
• Presence of multiple solar keratoses
• High levels of ultraviolet exposure such as outdoor workers: Outdoor workers have up to 5 times higher risk compared with people who have only worked indoors.4
• Solarium use: The risk of SCC is twice as high in people who have used a solarium before the age of 25, compared with people who have never used a solarium4
• Smoking, in particular for SCC of the lip.9 Current smokers are up to three times more likely to develop SCC than non-smokers.9

Symptoms and signs of squamous cell carcinoma

In men, squamous cell carcinoma occurs most commonly on the head and neck. In women, the arms are affected most, followed by the head and neck.9 Most squamous cell carcinomas grow from pre-existing solar keratoses (although the chance of any given solar keratosis turning into a squamous cell carcinoma is very low).1

Symptoms of SCC may include:

• thickened red, scaly spot
• rapidly growing lump, with a crust on its surface
• a sore which does not heal after several weeks or months

In some cases, SCC may be tender to touch.

SCC can occasionally be difficult to diagnose. It usually appears in areas of sun damage and solar keratoses, and is easily mistaken for an overgrown solar keratosis. In cases where the diagnosis is unclear, a punch or shave biopsy may be required to establish the diagnosis and suitable treatment.10

Progression

If untreated, squamous cell carcinoma will usually enlarge gradually, leading to bleeding and ulceration. As it grows, it may become more tender to touch.9 

Large SCCs sometimes grow into the tissue surrounding nerves in the skin. This is known as perineural spread, and means that there is a higher risk of the SCC:

• being difficult to cure
• returning after treatment
• spreading to other organs.9 This type of spread occurs in 4 per cent of SCC cases.5

Different types of SCC progress in other ways.

• Superficial SCC (also called Bowen's disease or squamous cell carcinoma in situ) affects the top layer of skin and appears as a red rough/scaly patch rather than a lump with a crust. It usually grows very slowly — the patient may have difficulty noticing changes. Bowen's disease rarely progresses to invasive squamous cell carcinoma and  is usually easy to treat.
• Keratoacanthoma is a rapidly-growing form of squamous cell carcinoma which can appear over a period of weeks. It is unusual for keratoacanthoma to become invasive and in many instances it disappears by itself. This does not always happen, so it is usually treated by surgical removal.

Treatment

Squamous cell carcinoma is usually treated effectively with surgical removal (also called excision). The entire cancer must be removed with a margin of at least 2mm (but sometimes more) of normal skin around its edges.5

Bowen's disease affects only the upper part of the skin and can be treated from the surface using cryotherapy (freezing) or fluorouracil, a chemotherapy cream. Each of the treatment options has advantages and disadvantages and should be discussed with a doctor.

Prevention

Primary prevention: for people who have never had a squamous cell carcinoma

Because the majority of squamous cell carcinomas are caused by ultraviolet radiation, avoiding excessive sun exposure is the most important measure for prevention. The risk of squamous cell carcinoma is increased by sun exposure in later life, so reduction of sun exposure at any age can help reduce the risk.

When the ultraviolet index is greater than 3, recommended methods for reducing sun exposure include:

• wearing long sleeves and pants, hats and sunglasses
• using broad spectrum sunscreen with SPF of 30 or greater
• seeking shaded locations

Other measures to reduce SC risk include:

• Avoiding or giving up smoking
• Avoiding solarium use

There is some evidence that a diet rich in leafy green vegetables can reduce the risk of SCC,9 and one study has found lower rates of SCC in people who regularly take non-steroidal anti-inflammatory drugs such as aspirin.11

Secondary prevention: to prevent future squamous cell carcinomas in people who have previously had an SCC

Regular skin checks can prevent squamous cell carcinoma through the detection and treatment of pre-cancerous solar keratoses. When squamous cell carcinoma is detected at a skin cancer check-up, it is more likely to be early and therefore easier to treat and less likely to result in serious medical consequences or death.

Daily use of sunscreen significantly reduces the risk of squamous cell carcinoma in people who have already had one.12

Vitamin B3 (taken in the form of nicotinamide 1000mg daily) reduces the development of future squamous and basal cell carcinomas by 23 per cent.13

There are case studies of HPV vaccine being successfully used to treat and prevent the recurrence of SCC in patients unsuitable for surgical treatment.14

• 1. a. b. Cancer Council Australia, 2019. SunSmart position statements: Risks and benefits of sun exposure. https://www.cancer.org.au/policy-and-advocacy/position-statements/sun-s…
• 2. a. b. Australian Institute of Health and Welfare, 2016. Skin cancer in Australia. https://www.aihw.gov.au/reports/cancer/skin-cancer-in-australia/content…
• 3. Leiter U, Garbe C 2008, Epidemiology of melanoma and nonmelanoma skin cancer: the role of sunlight. Advances in Experimental Medicine and Biology, vol. 624, pp. 89–103.
• 4. a. b. c. d. Cancer Council. Risk factors/epidemiology [Version URL: https://wiki.cancer.org.au/skincancerstats_mw/index.php?title=Risk_fact…, cited 2019 Apr 21]. Available from: https://wiki.cancer.org.au/skincancerstats/Risk_factors/epidemiology. In: Cancer Council Australia. Skin Cancer Statistics and Issues. Sydney: Cancer Council Australia. Available from: http://wiki.cancer.org.au/skincancerstats/
• 5. a. b. c. d. Cancer Council Australia, 2015. Optimal care pathway for basal cell carcinoma and squamous cell carcinoma. https://www.cancervic.org.au/downloads/health-professionals/optimal-car…
• 6. Cancer Council. Skin cancer incidence and mortality [Version URL: https://wiki.cancer.org.au/skincancerstats_mw/index.php?title=Skin_canc…, cited 2019 Apr 20]. Available from: https://wiki.cancer.org.au/skincancerstats/Skin_cancer_incidence_and_mo…. In: Cancer Council Australia. Skin Cancer Statistics and Issues. Sydney: Cancer Council Australia. Available from: http://wiki.cancer.org.au/skincancerstats/
• 7. Royal Australian College of General Practitioners 2018. Skin cancer, in Guidelines for preventive activities in general practice, 9th edition. https://www.racgp.org.au/clinical-resources/clinical-guidelines/key-rac…
• 8. Centeno JA, Mullick FG, Martinez L, et al. Pathology related to chronic arsenic exposure. Environ Health Perspect. 2002;110 Suppl 5(Suppl 5):883–886. doi:10.1289/ehp.02110s5883
• 9. a. b. c. d. e. f. Basal cell carcinoma, squamous cell carcinoma (and related lesions) – a guide to clinical management in Australia. Cancer Council Australia and Australian Cancer Network, Sydney. 2008
• 10. Cancer Council. Skin cancer types [Version URL: https://wiki.cancer.org.au/skincancerstats_mw/index.php?title=Skin_canc…, cited 2019 Apr 25]. Available from: https://wiki.cancer.org.au/skincancerstats/Skin_cancer_types. In: Cancer Council Australia. Skin Cancer Statistics and Issues. Sydney: Cancer Council Australia. Available from: http://wiki.cancer.org.au/skincancerstats/
• 11. Nonsteroidal anti-inflammatory drugs and the risk of actinic keratoses and squamous cell cancers of the skin Butler, Gregory J. et al. Journal of the American Academy of Dermatology , Volume 53 , Issue 6 , 966 - 972 DOI: 10.1016/j.jaad.2005.05.049
• 12. Green A, Williams G, Neale R, Hart V, Leslie D, Parsons P et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 1999; 354(9180):723-729. DOI: https://doi.org/10.1016/S0140-6736(98)12168-2
• 13. Chen A et al. A phase 3 randomized trial of nicotinamide for skin cancer prevention. N Engl J Med 2015; 373:1618-1626 Link www.nejm.org/doi/full/10.1056/NEJMoa1506197
• 14. Nichols AJ, Allen AH, Shareef S, Badiavas EV, Kirsner RS, Ioannides T. Association of Human Papillomavirus Vaccine With the Development of Keratinocyte Carcinomas. JAMA Dermatol. 2017;153(6):571–574. doi:10.1001/jamadermatol.2016.5703