Abstract
Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen’s disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.
Highlights
Cutaneous squamous cell carcinoma is the second most common nonmelanoma skin cancer (NMSC) after basal cell carcinoma (BCC). cSCC accounts for 20% of cutaneous malignancies and about 75% of all deaths due to skin cancer, excluding melanoma
This review presents a literature overview of cSCC from pathophysiology to novel therapeutic approaches
This hypothesis is supported by the identification of an increased viral load in actinic keratosis (AK) compared to cSCCs [127,128]
Summary
Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer (NMSC) after basal cell carcinoma (BCC). cSCC accounts for 20% of cutaneous malignancies and about 75% of all deaths due to skin cancer, excluding melanoma. CSCC accounts for 20% of cutaneous malignancies and about 75% of all deaths due to skin cancer, excluding melanoma. CSCC can favor local cutaneous destruction involving soft tissue, cartilage, and bone. The surgical approach is the first-line treatment for invasive cSCC, other techniques (i.e., curettage, electrodessication, cryosurgery, lasers, and photodynamic therapy) are available for noninvasive forms. The multistage process that leads to cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes [2,7]. The immune checkpoint inhibitor cemiplimab is approved in the USA and Europe as a systemic treatment for metastatic and locally advanced cSCC not amenable to surgical or RT treatment. This review presents a literature overview of cSCC from pathophysiology to novel therapeutic approaches
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