Nonmelanoma skin cancer – from actinic keratosis to cutaneous squamous cell carcinoma

Abstract

Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life-threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression. In addition to a broad armamentarium of procedures as well as pharmaceutical treatment options, primary prevention through diligent UV protection likewise plays a crucial role. New clinical, histomorphological, or molecular classifications are needed to be able to reliably stratify patients based on their individual risk. Especially in light of socio-economic aspects, such a step might prevent over- and undertreatment of an ever-growing patient population and help develop treatment concepts based on individual patient needs.

Topical Diclofenac Reprograms Metabolism and Immune Cell Infiltration in Actinic Keratosis

“…In our previous work, we clearly demonstrated in a murine B16 melanoma model, that inhibition of lactate production by LDHA downregulation improves immunosurveillance and restrains tumor in an IFN-γ dependent manner (18). Strong infiltration with CD8+ T cells was also described after topical treatment with ingenol mebutate, a standard drug for AK (39, 40), but in this study the number of CD4+ T cells and myeloid cells was also increased, suggesting an unspecific inflammatory reaction.…”

Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate

“…Their peripheral CD4 + T cell numbers were above 594 cells/μl (Supplemental Table 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.126027DS1). Following the topical application of ingenol mebutate on skin lesions on the right forearm, skin biopsies were obtained at day 1 (for patient 5) or day 2 (for patients [1][2][3][4]. For a paired control sample, a skin biopsy was obtained from an untreated region of the contralateral (left) forearm (day 0 for control).…”

“…For a paired control sample, a skin biopsy was obtained from an untreated region of the contralateral (left) forearm (day 0 for control). An additional longitudinal biopsy sample was collected, coincident with scheduled skin biopsies, at day 10 (for patients [1][2][3][4] or at day 22 (for patient 5) from an area close to the initial day 2 biopsy site from the ingenol mebutate gel-treated arm. Tissue biopsies were divided and placed into RNAlater and into buffered formalin.…”

“…Actinic keratosis (AK), a precancerous skin lesion, commonly develops with age and is usually induced by years of exposure to the sun (1)(2)(3). Some of these AK lesions can progress to squamous cell carcinoma (SCC) (4). As antiretroviral therapy-suppressed (ART-suppressed) HIV-positive individuals are getting older, an increased incidence of SCC is being reported among individuals with HIV infection (5).…”

Evaluating the Noninferiority of a New Photodynamic Therapy (Flexitheralight) Compared With Conventional Treatment for Actinic Keratosis: Protocol for a Phase 2 Study

“…The malignant potential and impossibility of predicting which AK lesions will evolve into SCC have led to the common consensus that AK lesions must be treated [11]. The most commonly used treatments for AK are cryotherapy, topical chemotherapy, and, more recently, photodynamic therapy (PDT) [2,12-16].…”