Keratinocyte Carcinoma Research Articles

National Trends in Healthcare Expenditures for the Management of Skin Cancer in the United States.

Malignant melanoma and keratinocyte carcinomas account for a substantial proportion of healthcare expenditures in the United States. To estimate trends in the economic burden of skin cancer in the United States between 1996 and 2016. The Disease Expenditure Project and Global Burden of Disease databases were used to estimate annual total costs and population-standardized rates of change for skin cancer-related healthcare spending. Skin cancer expenditures totaled $23.4 billion in 2016, of which $1.4 billion (95% CI: $1.3-$1.6 billion) was melanoma-related and $22 billion (95% CI: $18-$28 billion) was keratinocyte carcinoma-related. Most spending on skin cancer management occurred in ambulatory care settings [60.7% (95% CI: 57.7%-64.3%) for melanoma and 87.8% (95% CI: 87.2%-88.2%) for keratinocyte carcinoma]. Pharmaceutical costs for melanoma have increased since 2010 to $365 million (95% CI: $327-$416 million), which represents 26.1% (95% CI: 22.6%-29.3%) of total melanoma expenditure. Skin cancer management in the United States is costly. Expenditures have increased substantially since 1996 without signs of plateauing in recent years.

Skin Cancer Diagnosis by Lesion, Physician, and Examination Type: A Systematic Review and Meta-Analysis.

Skin cancer is the most common cancer in the US; accurate detection can minimize morbidity and mortality. To assess the accuracy of skin cancer diagnosis by lesion type, physician specialty and experience, and physical examination method. PubMed, Embase, and Web of Science. Cross-sectional and case-control studies, randomized clinical trials, and nonrandomized controlled trials that used dermatologists or primary care physicians (PCPs) to examine keratinocytic and/or melanocytic skin lesions were included. Search terms, study objectives, and protocol methods were defined before study initiation. Data extraction was performed by a reviewer, with verification by a second reviewer. A mixed-effects model was used in the data analysis. Data analyses were performed from May 2022 to December 2023. Meta-analysis of diagnostic accuracy comprised sensitivity and specificity by physician type (primary care physician or dermatologist; experienced or inexperienced) and examination method (in-person clinical examination and/or clinical images vs dermoscopy and/or dermoscopic images). In all, 100 studies were included in the analysis. With experienced dermatologists using clinical examination and clinical images, the sensitivity and specificity for diagnosing keratinocytic carcinomas were 79.0% and 89.1%, respectively; using dermoscopy and dermoscopic images, sensitivity and specificity were 83.7% and 87.4%, and for PCPs, 81.4% and 80.1%. Experienced dermatologists had 2.5-fold higher odds of accurate diagnosis of keratinocytic carcinomas using in-person dermoscopy and dermoscopic images compared with in-person clinical examination and images. When examining for melanoma using clinical examination and images, sensitivity and specificity were 76.9% and 89.1% for experienced dermatologists, 78.3% and 66.2% for inexperienced dermatologists, and 37.5% and 84.6% for PCPs, respectively; whereas when using dermoscopy and dermoscopic images, sensitivity and specificity were 85.7% and 81.3%, 78.0% and 69.5%, and 49.5% and 91.3%, respectively. Experienced dermatologists had 5.7-fold higher odds of accurate diagnosis of melanoma using dermoscopy compared with clinical examination. Compared with PCPs, experienced dermatologists had 13.3-fold higher odds of accurate diagnosis of melanoma using dermoscopic images. The findings of this systematic review and meta-analysis indicate that there are significant differences in diagnostic accuracy for skin cancer when comparing physician specialty and experience, and examination methods. These summary metrics of clinician diagnostic accuracy could be useful benchmarks for clinical trials, practitioner training, and the performance of emerging technologies.

Combined Topical 5-Fluorouracil and Calcipotriene Effectively Treats Superficial Keratinocyte Carcinomas: A retrospective cohort study from two academic centers

Combined Topical 5-Fluorouracil and Calcipotriene Effectively Treats Superficial Keratinocyte Carcinomas: A retrospective cohort study from two academic centers

MCPIP1 modulates the miRNA‒mRNA landscape in keratinocyte carcinomas

BackgroundMonocyte Chemotactic Protein 1-Induced Protein 1 (MCPIP1, also called Regnase-1) is a negative modulator of inflammation with tumor-suppressive properties. Mice with keratinocyte-specific deletion of the Zc3h12a gene, encoding MCPIP1, (Mcpip1eKO mice) are more susceptible to the development of epidermal papillomas initiated by 7,12-dimethylbenz[a]-anthracene (DMBA) and promoted by 2-O-tetradecanoylphorbol-13-acetate (TPA).MethodsThe aim of this study was to investigate the MCPIP1 RNase-dependent microRNA (miRNA)‒mRNA regulatory network in chemically induced squamous cell carcinoma (SCC)-like skin papillomas. Next-generation sequencing (NGS) coupled with bioinformatic analysis was used to shortlist the MCPIP1-dependent changes in protein-coding genes and miRNAs. The expression levels of the selected miRNAs were analyzed by quantitative PCR in human keratinocytes with MCPIP1 silencing. Functional studies were performed in human keratinocytes transfected with appropriate miRNA mimics. The DIANA-microT-CDS algorithm and DIANA-TarBase v7 database were used to predict potential target genes and identify the experimentally validated targets of differentially expressed (DE) miRNAs.ResultsRNA sequencing (RNA-Seq) analysis of control and Mcpip1eKO DMBA/TPA-induced papillomas revealed transcriptome changes, with 2400 DE protein-coding genes and 33 DE miRNAs. The expression of miR-223-3p, miR-376c-3p, and miR-139-5p was confirmed to be dependent on MCPIP1 activity in both murine and human models. We showed that MCPIP1 directly regulates the expression of miR-376c-3p via direct cleavage of the corresponding precursor miRNA. The pro-proliferative activity of miR-223-3p, miR-376c-3p, and miR-139-5p was experimentally confirmed in SCC-like keratinocytes. Bioinformatic prediction of the mRNA targets of the DE-miRNAs revealed 416 genes as putative targets of the 18 upregulated miRNAs and 425 genes as putative targets of the 15 downregulated miRNAs. Further analyses revealed the murine interactions that are conserved in humans. Functional analysis indicated that during the development of cutaneous SCC, the most important pathways/processes mediated by the miRNA‒mRNA MCPIP1-dependent network are the regulation of inflammatory processes, epithelial cell proliferation, Wnt signaling, and miRNA transcription.ConclusionsLoss of MCPIP1 modulates the expression profiles of 33 miRNAs in chemically induced Mcpip1eKO papillomas, and these changes directly affect the miRNA‒mRNA network and the modulation of pathways and processes related to carcinogenesis.

Racial and ethnic differences in healthcare access and utilization among U.S. adults with melanoma and keratinocyte carcinomas in the NIH All of Us Research Program.

There is a paucity of information on racial and ethnic disparities relating to barriers to care in healthcare access and utilization in patients with cutaneous malignancies. We conducted a cross-sectional analysis of adults with melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) in the National Institutes of Health (NIH) All of Us Research Program collected between May 2018 and July 2022. Participants included adults (aged 18 or older) with cutaneous malignancy who completed the Health Care Access and Utilization survey. We identified 5,817 adults who were diagnosed with BCC (67%), cSCC (28.9%), and melanoma (23.9%). Non-Hispanic Black (NHB) and Hispanic patients were more likely than non-Hispanic White (NHW) patients to delay a primary care visit due to cost (p = 0.005 and p = 0.015, respectively). NHB patients were also more likely to delay care due to lack of transportation (p < 0.001). NHB and Hispanic patients were more likely to place importance on seeing a provider from the same background (NHB p < 0.002; Hispanic p = 0.002) and also were more likely to report never being able to see such a provider (NHB p < 0.001; Hispanic p = 0.002). Medicaid/Medicare patients, non-college graduates, and those with lower incomes also faced increased barriers to care, including delays due to cost and transportation issues. People of color with cutaneous malignancies are more likely to delay care in seeing primary care providers due to cost or transportation issues. This study provides important insights on disproportionate healthcare usage among racial/ethnic groups that may help mitigate healthcare disparities.

Utilizing fractional lasers and tirbanibulin ointment to treat squamous and basal cell carcinomas

Keratinocyte carcinoma is the most common form of cancer in the United States. Often treated by surgical excision, electrodessication and curettage, or Mohs surgery, treatment can frequently leave patients with a scar and can be time consuming and inconvenient for both patients and healthcare providers. Utilizing non-ablative fractional laser therapy followed by tirbanibulin ointment, we treated 30 basal and/or squamous cell carcinomas on 23 patients over the age of 50 with varying skin types. Multiple areas of the face and body, and carcinomas at differing stages, were treated. We maximized the depth of penetration of the fractional laser by using bulk heating methods while simultaneously optimizing cosmetic results. This is an ongoing study as we continue to track the progress of our participants. Thus far, no clinical or histological recurrence of carcinoma has been found in any of the treated sites.

Keratinocyte Carcinoma: Canadian Landscape and an Evidence-based Approach to Follow-up

Dermatologists play a vital role in the early detection, prevention and effective management of skin cancer in patients with a prior history of the disease. Regular monitoring and timely interventions greatly enhance the overall prognosis and quality of life for patients with skin cancer. Dermatologists possess the requisite expertise to accurately diagnose and oversee the management of cutaneous skin cancers. Skin cancer screening via total body skin exam (TBSE) is often considered one of the safest, easiest, and most cost-effective tests in medicine. Despite dermatologists’ ability to offer such invaluable care for this patient population, offering routine skin checks for all patients with a prior history of skin cancer becomes exceptionally challenging given the high demand for dermatology care across Canada. It is important for dermatologists to maximize the efficiency of care during TBSEs by adhering to evidence-based guidelines when determining the frequency and duration of follow-up. These guidelines also provide a solid foundation for discussions with patients regarding the rationale for discharge back to their primary care provider.

Remote cutaneous confocal microscopy: A multicentric prospective study evaluating diagnostic accuracy for melanoma and keratinocyte carcinoma in tertiary settings

Cutaneous confocal microscopy (CCCM) facilitates in vivo visualisation of skin at a cellular level. Use of a "store and forward" approach for remote CCM interpretation (Remote-CCM) across multiple sites has not been tested and may increase access to non-invasive diagnosis. To test the diagnostic accuracy and safety of Remote-CCM. We prospectively recruited lesions selected for biopsy for skin malignancy across five Australian tertiary dermatology centres. CCM, clinical and dermoscopy images were acquired pre-biopsy and accessed by a cloud-based platform for interpretation by CCM readers. CCM diagnosis was compared to histopathology results. Amongst the 201 lesions included, melanoma was the most common malignancy (34/72, 47.2%). Of the 89 lesions (44.8%) potentially 'saved' from biopsy, 80 (90%) were truly benign lesions and 9 (10.1%) were missed malignant lesions of MIS (n=7) and SCC (n=2). No invasive melanomas were missed. Sensitivity of remote-CCM for detection of malignancy was 89% (95%CI 79-95%) and specificity was 64% (95%CI 55-73%). The study recruited from high-risk populations and excluded lesions that were not biopsied. Remote-CCM has comparable accuracy to bedside-CCM and safely reduces unnecessary biopsies. Potential SCCs are not appropriate for remote-CCM. Follow-up of borderline melanocytic lesions is recommended.

Histopathologic classification of actinic keratosis severity is associated with burden of keratinocyte carcinoma

Histopathologic classification of actinic keratosis severity is associated with burden of keratinocyte carcinoma

Immunosuppression regimen and latitude impact keratinocyte carcinoma risk in U.S. liver transplant recipients

Immunosuppression after solid organ transplantation is associated with an increased risk of keratinocyte carcinoma (KC). Despite its established morbidity, KC risk in liver transplant (LT) recipients is understudied, including the contribution of immunosuppression regimen and latitude. A retrospective cohort of 9,966 adult first LT alone recipients alive with their native allograft at 1-year post-LT without prior KC between 2007 and 2016 were identified using linked data from the Organ Procurement and Transplantation Network and Medicare administrative claims. The primary exposures were immunosuppression regimen and latitude of residence. The primary outcome was incident, de novo KC occurring at least 1-year after LT. Adjusted Cox regression analysis stratified by transplant center was used in all analyses. The cohort was 63.4% male, 70.2% White and with median age 61 years (interquartile range, IQR, 54–66) at transplant. Calcineurin inhibitor (CNI) with anti-metabolite combination was independently associated with incident KC when measured as intention-to-treat (adjusted hazard ratio (aHR) 1.21 vs. CNI monotherapy, 95% CI 1.02–1.43, p = 0.026), in a time-updating as-treated analysis (aHR 1.61, 95% CI 1.34–1.93; p < 0.001) and when measured as cumulative exposure (aHR 1.13 per 6-month increase, 95% CI: 1.02–1.33; p = 0.027). More southern latitude of residence was also independently associated with incident KC with an aHR of 1.26 per 5°N decrease towards the Equator (95% CI: 1.08–1.47, p = 0.003). We demonstrate independent effects of CNI with antiM immunosuppression regimen and latitude of residence on the risk of post-LT KC, which will better inform screening practices and immunosuppression management.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Interobserver agreement on line-field confocal optical coherence tomography image markers in keratinocyte carcinomas and precursor lesions

Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger’s kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06–0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.

54622 A characterization of US patients with keratinocyte carcinomas using DataDerm

54622 A characterization of US patients with keratinocyte carcinomas using DataDerm

50563 Anatomical Locations of Keratinocyte Carcinomas Among United States Veterans Affairs Healthcare System Patients in Minnesota

50563 Anatomical Locations of Keratinocyte Carcinomas Among United States Veterans Affairs Healthcare System Patients in Minnesota

53226 Validation of keratinocyte carcinoma diagnosis and treatment codes among veterans with HIV

53226 Validation of keratinocyte carcinoma diagnosis and treatment codes among veterans with HIV

Photodynamic therapy reduces the burden of small ultraviolet-induced epidermal clones in human and mouse skin.

Actinic keratoses (AKs) and keratinocyte carcinomas (KCs) arise from prolonged UV exposure, with precursor UV-induced clonal mutations (CMs) appearing in sun-damaged skin. Photodynamic therapy (PDT) is a common field treatment for AKs and early KCs, but its impact on subclinical CMs is unknown. This study examines CMs using targeted ultra-deep sequencing on epidermal samples. By comparing skin before and after PDT in five patients and a mouse model of chronic UV carcinogenesis, a significant reduction in low-frequency mutations post-treatment was revealed. These findings highlight PDT’s potential in modifying subclinical damage and propose low-variant allele frequency CMs as biomarkers for field treatment efficacy.

Hygrophilla Auriculata Extract Loaded Microemulsion gel for treatment of skin cancer

Globally, skin cancer is the most common type of cancer and is on the rise. It is broadly divided into Melanoma and Non-melanoma skin cancer, or Keratinocyte carcinoma, which are malignancies produced from melanocytes and epidermal cells, respectively. One of the most deadly malignant illnesses, cancer can spread to other tissues and organs and exhibit unchecked and aberrant cell division. Therefore, achieving a safe formulation for the treatment of skin cancer is important. The aim of this research is to formulate the Hygrophila Auriculata Flower extract Loaded Microemulsion Gel with small droplet size, high drug concentration, and high stability for skin application. A magnetic stirrer was used to create the Hygrophila Auriculata Flower extract Loaded Microemulsion, which was examined for morphology, clarity, dilution, zeta potential, particle size, stability, and chromatography. The cytotoxicity study of the formulation was performed in A431 cells and compared with a marketed formulation. The smallest particle size of the emulsion droplets improves the bioavailability of the drug, playing a vital role in skin penetration and effectiveness against skin cancer. Hence, the study predicts that the Hygrophila Auriculata Flower extract Loaded Microemulsion Gel could be effective for the treatment of skin cancer in the future.

Epidemiologic trends in cutaneous squamous cell carcinoma from 2011 to 2021 at All Africa Leprosy, Tuberculosis, and Rehabilitation Training Center (ALERT) in Addis Ababa, Ethiopia

Cutaneous squamous cell carcinoma (cSCC) is the most common keratinocyte carcinoma in dark-skinned ethnic groups. Available studies are primarily focused on white populations, with fewer data available for black Africans, including Ethiopians. Therefore, less priority may be given to treatment and prevention in this population. To determine the prevalence and risk factors of cSCC among patients presenting to All Africa Leprosy, Tuberculosis, and Rehabilitation Training Center , Addis Ababa, Ethiopia. A literature review was performed to determine existing knowledge. A retrospective descriptive cross-sectional study was then conducted based on stored data of confirmed cases of cSCC from 2011 to 2021 at ALERT. Demographics, other parameters related to cSCC (size, anatomic location, degree of differentiation, metastasis, and recurrence), and potential risk factors including scars, burns, HIV status, xeroderma pigmentosum, and leprosy were collected and entered on a prepared data extraction sheet and analyzed using SPSS version 25 manufactured by IBM. Among 15,075 total pathologic samples reviewed, 3.8% (n=570) were reported histopathologically as invasive cSCC (n=437), keratoacanthoma, or (squamous cell carcinoma in-situ (Bowen disease). 50.3% (n=287) occurred in female, and the mean age of affected patients was 50.1years (SD 17.2). Nearly 70% were reported after >1year of symptoms, including morphologic change, ulceration, and nonhealing wound. HIV status was not universally screened but was positive in 9.8% (46/437). Cases were commonly found to occur on the lower extremities (X2=2.7196, Pr=0.099) and >4cm in size (46.3%). Among 274 cases with adequate histologic description, 82.5% (n=226) were well-differentiated. Loco-regional metastases comprised 6.0% (n=34) and 46.7% (n=266) had ulceration. The biologic significance of ulceration in this population is unclear. Ulceration may indicate chronic wounds or Marjolin's ulcers. High rates of metastasis call for a better understanding of risk factors, preventive measures, and early diagnosis. This model of research may serve as a foundation for future nationwide investigations through the Federal Ministry of Health of Ethiopia's Disease Prevention and Control Directorate.

Porokeratoses: an update on pathogenesis and treatment.

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second-hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%-16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging.

Micro RNA Dysregulation in Keratinocyte Carcinomas: Clinical Evidence, Functional Impact, and Future Directions.

The keratinocyte carcinomas, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs, assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.