Cutaneous squamous cell carcinoma


Lifetime risk of squamous cell cancer of the skin 9-14% among men and 4-9% among women.

With more than 1 million new cases annually and mortality now exceeding that for melanoma, it represents a major healthcare burden.

Its most important risk factors are cumulative exposure to ultraviolet radiation, age, and systemic immunosuppression.

Innate, acquired, and iatrogenic immunosuppression increases the risk of CSCC, the number of lesions, and the aggressive of tumors.

Acquired immunosuppression: solid organ transplant, HIV, CLL, lymphoma, or long-term immunosuppressive therapy increases the risk of CSCC.

Chronic inflammation from burn scars, chronic sinus tracts, or inflammatory dermatoses, smoking, hypothyroidism, drugs (such as voriconazole, hydrochlorothiazide, BRAF inhibitors, tumor  necrsosis factor inhibitors is as well as HPV are risk factors.

Approximately 20% of skin cancers.

CSCC is the second most common non-melanoma skin cancer in the world representing approximately 20% of all non-melanoma skin cancers and 20% of all skin cancer-related mortality.

In 2019 worldwide it was approximately 2.4 million new cases and 56,000 deaths.

From 1990 through 1990 the overall incidence of cutaneous quality of squamous cell carcinoma has increased by more than 200%.

CSCCs increases are associated with an aging population, higher levels of sun exposure, the use of tanning beds, increase focus on skin cancer screening and detection, a growing proportion of patients with organ, transplants and underlying immuno suppression.

An estimated 186-420,000 cases of dermally invasive cutaneous squamous cell carcinoma are diagnosed annually in the US.

Has a surgical cure rate upwards of 95%, but there were estimated 4000-9000 disease related deaths in the US in 2012.

Presents as erythematous papule, plaque, or nodule on sun exposed skin.

Male predominance and mean onset seventh decade.

Squamous cell cancer of the skin occurs twice as frequently with men older than 50 years compared with women of the same age.

The risk increases dramatically with age and the incidence among older persons than 75 years is 5 to 10 times that among younger individuals 55 years or less.

Individuals with first-degree relatives with squamous cell cancer of the skin may have an increased risk of the disease as they share similar cutabneous phenotype, environmental, and genetic factors.

Inherited phenotypic changes, including light skin, red or blonde hair, and light colored eyes are associated with increased risk of squamous cell carcinoma of the skin.

Family history of cutaneous squamous cell carcinoma, has a 2 to 4 times increased risk than persons without a family history.

Disorders which are inherited such as xoderma pigmentosum, epidermolysis bullosa,, albinism have increased risk of cutaneous squamous cell carcinoma, often with earlier age of onset.

Germline mutations and single nucleotide polymorphisms put people at risk and squamous cell carcinoma with high mutational burden are commonly seen with TP 53, NOTCH1/2, CDKN2A,  PI3K, and cell cycle pathways.

Incidence is increasing.

More common in light skin, non-Hispanic whites.

More common in men than women with a 3 to 1 ratio.

Rare in African or Asian peoples.

Patients typically present with scaly, erythematous, or bleeding lesions, most often on sun exposed areas.

Cutaneous, squamous cell carcinoma, is the most common type of skin cancer in Black persons and the second most common in White, Asian and Hispanic persons.

The incidence of squamous cell carcinoma of the skin in Black persons is estimated to be 3 cases for 100,000, as compared with 150 to 360 per hundred thousand among White persons in the US.

Incidence increases with increasing age and geographic proximity to the equator.

Persons who live closer to the equator tend to present at a younger age compared to those who live more distant.

95% are squamous cell cancers of the skin found in the head and neck area.

Age adjusted incidence of squamous cell carcinoma has grown by 50 to 200 percent over the past 10 to 30 years.

Significant risk factors include: cumulative exposure to UV light and chronic immunosuppression most significantly in patients with solid organ transplants.

UV radiation most common cause of this type of skin cancer.

UV B radiation from sunlight principally responsible, with UVA radiation adding to the risk.

UVB causes  direct DNA damage due to the formation of dipyrimidine dimers that lead to malignant transformation.

UVA has a role through indirect DNA damage in the formation of free radicals.

Psoralen plus UVA and tanning beds, both primary emitters of UVA are associated with increased risk of cutaneous squamous cell carcinoma.

Tanning of any duration increases the relative risk of cutaneous squamous cell carcinoma by 1.67.

Increased environmental risk occurs with ionizing radiation, and exposure to arsenic or radon.

Associated with a 7 fold increase in incidence in patients on long-term hydrochlorothiazide..

Regular sunscreen use prevents cutaneous squamous cell carcinoma and melanoma (Robinson JK et al).

Prevention is accomplished through limiting sun exposure, through the use of sunscreen and sun protective clothing, and in certain high risk patients there is a role for oral retinoids, particularly


Generally associated with a favorable prognosis.

Prognostic factors include diameter, depth and poor differentiation of the lesion.

Can develop anywhere on the body, including the genitals.
Most often in the areas exposed to UV radiation, such as the face, lips, ears, scalp, shoulders, neck, back of the hands and forearms.
Lesions can appear as firm, red nodules or persistent scaly patches of skin with irregular borders that may crust over or bleed.
Squamous cell cancers can resemble warts or open sores that won’t heal.
Lesions may develop into an elevated growth with the central depression that can bleed and increase in size.
Squamous cell cancer‘s look different on each patient.

Poor prognosis factors include a lesion larger than 2 cm in diameter, greater than 2 mm depth of involvement, poorly differentiated tumor, one that is eroded, and perineural involvement.

Immunosuppressed patients are at increased risk for metastases.

The estimate for metastases among organ transplant recipients is 7.3% on the body and 11% in the head and neck areas.

The presence of metastasis has a reduction in five year survival rate ranging from 50 to 83%, and may be even lower in immuno suppressed populations.

Most cases can be cured with a surgical excision or, for selected low-risk lesions ablative modalities such as electro dissection and curettage.

Curettage and electodessication is an option for patients not eligible for invasive procedure:  It is appropriate when the squamous cell carcinoma has prominent borders, is low risk, and is limited to the top layer of skin.
The tissue is scraped off the affected area and an electric needle destroys any remaining cancer cells.
Curettage and electrodesiccation does not have as high cure rate as surgical options such as Mohs surgery.
Laser surgery is commonly use for squamous cell cancers on sensitive areas of the body, such as the eyelids or face, or in those with an impaired immune system that cannot handle invasive surgery.
Cryosurgery is used more often for a pre-cancerous lesions such as actinic keratosis, but can be used for skin cancer if a patient is not a candidate for other procedures, or has a bleeding disorder.
Radiation can be use for squamous cell carcinomas that are larger or located where they would be difficult to remove surgically.
Radiation treatment is an option for patients who are older or in poor health, or for whom surgery is not recommended. In advance squamous cell cancers.
Radiation may be used after surgery to ensure that all cancer cells have been destroyed, lowering the risk of recurrence.
Radiation is not commonly used to treat younger patients because of the risk of new skin cancers in a previously treated area.
Radiation is not recommended for patients with certain connective tissue diseases.
Mohs surgery is completed in stages while patient waits for lab results, which are obtained immediately on site.
Mohs procedure is recommended for advanced squamous cell cancers,particularly those at risk for recurrence, when the extent of the cancer is known, or the affected areas near the eye, central area of the face, ears, or fingers.
Mohs surgery is cost-effective because in most cases the entire process is done in one visit.
The cure rate for most surgery is approximately 98%.

A minority of cases are complicated by significant morbidity (3%).

Local recurrence of lesions occurs in 5.2%, nodal metastases 1.5%, and disease specific death 2.1%.

Prognosis in African people has a higher mortality rate due to delay in diagnosis, and because lesions are more likely to occur sun protected areas, including the scalp.

Iimmunosuppressed patients are an increased risk for metastasis.

The majority of squamous cell cancers in individuals of African descent arise from pre-existing inflammatory skin diseases or burn injuries.

In areas of US with the highest UV radiation mortality rivals that of melanoma, renal cell carcinoma, oropharyngeal carcinoma, leukemia, and lymphoma.

Patients are at risk for developing additional skin cancers including other cutaneous squamous cell carcinomas, basal cell carcinoma, and melanoma.

Risk factors that increase morbidity and mortality include: high risk location lesions that is, ears, lips, genitalia, chronically inflamed or radiated skin, large tumor diameter, keep invasion, recurrent tumor status, poor differentiation, perineural invasion, and host’s immunosuppressive state.

Rates of local recurrence or nodal metastases rise significantly as the number of cutaneous squamous cell carcinomas increase.


The majority of the localized, low risk cases of cutaneous, squamous cell carcinoma, can be managed with destructive or surgical techniques.

Curettage and electro desiccation or destructive techniques use for small, low risk lesions, excluding terminal hair bearing areas.

With such techniques, the cure rate is as high as 95% for appropriately selected lesions.

Wide local excisions can be performed for surgical margins of 4 to 6 mm, with cure rates of 90 to 98%.

For high risk cutaneous creamy, so carcinoma wider surgical margins from 6 to 10 mm are recommended.

Mohs micrographic surgery or resection with peripheral and deep assessment is recommended to achieve the control for high-risk or very high risk cutaneous squamous cell carcinomas.

Mohs micrographic surgery controls primary cutaneous cell carcinoma with very low rates of local recurrence at 1.2 to 4.1%, nodal metastasis, and disease specific death.

High risk features – positive margins, extensive perineural, involvement, or involvement of large or named nerves, requires adjuvant therapy.

Topical fluorouracil reduces risk for surgery for SCC

Daily application of topical fluorouracil for 4 weeks reduced the risk of developing squamous cell cancer requiring surgery by 75% in a population of high-risk older adults.

Patients with numerous squamous skin lesions likely to be immunosuppressed.

There is. exceptional responsiveness of cutaneous squamous cell carcinoma to immunotherapy is due to a high to mutational burden due to sun related ultraviolet mutagenesis.

Cemiplimab is associated with objective response rate in 44 to 50% of patients, along with durable disease control and improved patient reported quality of life.

Advanced disease responds to PD1 innhibitors cemiplimab and others.

Immune checkpoint inhibitors are the preferred regimen for systemic therapy alone in patient with locally advanced, recurrent, or metastatic cutaneous squamous cell carcinoma.

Overall response to targeted PD – 1 inhibition ranges from 34 to 52% for unresectable stage Ia disease and metastatic disease.

Pembrolizumab (Keytruda) approved for patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation.


KEYNOTE-629 trial, patients who were administered intravenous pembrolizumab at 200 mg every 3 weeks until progressive disease.

Pembrolizumab has durable antitumor activity and promising survival data in both locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma.

Results showed an ORR of 34% with pembrolizumab.


The median response duration had not yet been reached.

Neoadjuvant therapy with cemiplimab  is associated with a pathological complete response in a high percent of the patients with resectable cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma recurs, most commonly (70 to 80%), within two years after the diagnosis.

Oral nicotinamide shows a 30% reduction in new squamous cell carcinoma lesions and a  20% reduction in new basal cell carcinoma lesions at one year compared with placebo.

Prospective studies of oral retinoids reduce the number of new squamous cell carcinoma lesions up to 54% of patients, including organ, transplant recipients, and patients with skin cancer classified as chronic disease.



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