Squamous cell carcinoma of the skin causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2], Raviteja Guddeti, M.B.B.S. [3]

Overview

Squamous cell carcinoma is most commonly caused by long term exposure to sunlight and other forms of UV radiation. Male sex, fair skinned people, smokers, the elderly, and people who have previous history of a skin cancer are particularly prone to the development of this non-melanomatous skin cancer.

Causes

Squamous cell carcinoma (SCC) may occur in normal skin or in already damaged skin (injured or inflamed). Most skin cancers occur on skin that is repeatedly exposed to sunlight or another form of ultraviolet radiation. The effect is cumulative, with the amount of damage done to the skin building up over time. Although sun exposure is the major causative factor for most cases of squamous cell carcinoma there are some other causes for the development of this invasive form of skin cancer.

  • Therapeutic radiation : Psoralen plus ultraviolet A (PUVA) used in the treatment of psoriasis, and x-rays of head and neck increase the risk of squamous cell carcinoma. The likelihood that therapeutic radiation can lead to skin cancer also depends on other factors such as pigmentation of the skin and the total cumulative dose of radiation received. PUVA is particularly phototoxic and mutations in both TP53 tumor suppressor gene and the Ras oncogee are found in PUVA associated squamous cell carcinoma.In addition to being mutagenic, UVA in association with UVB is a potent suppressor of the cutaneous immune system.
  • People with a fair complexion, albinism, blue or gray eyes, and those with light colored hair are particularly prone to develop skin cancers as they lack the photo-protective melanin pigment.
  • Patients with the genetic disease called Xeroderma Pigmentosa have a deficiency of an enzyme that is essential for DNA repair. Inability to repair DNA that has been damaged by the sun leaves these patients prone to innumerable squamous cell carcinomas. There is also an increased risk of oral cancers in people with polydysplastic epidermolysis bullosa and Bloom syndrome.
  • Arsenic, a harmful toxin, is a well known cause of squamous cell carcinoma.
  • The use of immunosuppressive drugs to prevent graft rejection in organ transplant recipients is associated with a 65 to 250 fold increased risk of developing SCC compared to the general population. Pretransplantation end-organ disease may also impact the development of post-transplantation SCC. For example among renal transplant patients the highest incidence of skin cancer is found in those with poly cystic kidney disease while the lowest incidence is observed in diabetic nephropathy.Cholestatic liver disease is found to have a higher association with skin cancers than other causes of liver failure post-transplantation.
  • 15% of patients with SCC have a viral etiology for the cause of their cancer. Human Papilloma Virus (HPV) is a well known potential cause of squamous cell carcinoma. This sexually transmitted virus has more than 100 strains reported so far. Some strains cause genital warts and whereas others are known to cause cancer of the vagina, cervix and penis.
  • Tobacco use is associated with the development of sqaumous cell carcinoma. Both smoked and smokeless forms of tobacco contain carcinogens called mutagens.
  • SCC of the head and neck is commonly associated with alcohol use. The use of alcohol is associated with a 40 fold increase in the risk of developing SCC of the head and neck. The use of tobacco and alcohol together increases the risk even further, up to 100 fold. Mutations in TP53 tumor suppressor gene has a positive correlation with the use of tobacco and alcohol. [1]

References

  1. Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J, et al. Sunburn and p53 in the onset of skin cancer. Nature. Dec 22-29 1994;372(6508):773-6


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