Squamous Cell Carcinoma, Cutaneous



Cutaneous squamous cell cancer is the second most common nonmelanoma skin cancer after basal cell carcinoma (1).


Nonmelanoma skin cancer is the most common malignancy worldwide. Historically, squamous cell carcinoma (SCC) has been thought to account for 20% of nonmelanoma skin cancers, thus being the second most common malignancy after basal cell carcinoma (2),(3). However, recent data indicate that the ratio of basal cell carcinoma to SCC is 1.0 in the U.S. Medicare population (1). An accurate incidence of cutaneous SCC is not known since this is not required to be reported to national cancer registries.


  • The average age for incidence is around 60 years, more common in men (4).
  • Incidence increases the closer the person gets to the equator or higher altitude (4).

Etiology and Pathophysiology

Some of the hereditary disorders have genes that are associated with cutaneous squamous cell cancer (5). They include:

  • Xeroderma pigmentosum (5)
  • Oculocutaneous albinism (5)
  • Epidermodysplasia verruciformis (5)
  • Genes mutated include: TP53, CDKN2A, NOTCH1, Ras, TP53 (most common gene involved in cutaneous SCC) (5)

Risk Factors

  • Most SCCs arise in:
    • Sun-damaged skin of elderly white individuals of European ancestry
    • Gender (more common in men)
    • Increasing age (average age of onset is the mid-60s)
    • Background of preexisting lesions of actinic keratosis (AK) (2)
    • UV radiation exposure (5),(6)
    • Preexisting conditions
    • Immunosuppression (5)
      • Solid organ transplantation (5)
      • HIV/AIDS, non-Hodgkin lymphoma, chronic lymphocytic leukemia have increasing rates of developing cutaneous squamous cell cancer (5).
  • Chronic skin conditions (5)
    • Burn scars, hidradenitis suppurativa, chronic osteomyelitis, discoid lupus erythematosus, lichen planus, lichen sclerosus et atrophicus
  • Inherited genetic conditions (5)
    • Albinism, epidermolysis bullosa, xeroderma pigmentosum
  • Ionizing radiation exposure (6)
  • Arsenic exposure (5),(6)
  • Ulcers (6)
  • Bowen disease (SCC in situ) (6)
  • Erythroplasia of Queyrat (SCC in situ of penis) (6)
  • HPV infection (6, 11, 16, 18) (6)
  • Treatment with BRAF inhibitors (vemurafenib and dabrafenib) (7)

General Prevention

  • Protect skin from sun exposure (5).
  • Wear sunscreen, hats, and UV protective clothing.
  • Vitamin B3 (nicotinamide) can repair DNA by preventing UVR-induced adenosine triphosphate depletion (5).

Commonly Associated Conditions

Actinic keratosis is the precursor of cutaneous squamous cell cancer, Bowen disease, erythroplasia of Queyrat (4).

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