High-risk Squamous Cell Carcinoma Research Articles

[Artículo traducido]]Revisión del rol de la cirugía micrográfica con cortes en parafina en el tratamiento de tumores cutáneos

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal-cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

Unconventional Remedies for Squamous Cell Carcinoma: A Journey into Alternative Treatments.

Squamous cell carcinoma (SCC) is the second most common form of skin cancer and is typically found on sun-exposed skin. Risk factors include ultraviolet radiation exposure, older age, fairer complexion, smoking, and immunosuppression. SCC is a slow-growing tumor with the possibility of metastasis if not treated. The clinical presentation can range from a dry, scaly erythematous patch or plaque to a firm hyperkeratotic papule, plaque, or nodule, depending on the histological type via biopsy. The first-line therapies for SCC removal are standard excision and Mohs microscopic surgery; however, there are novel and alternative non-surgical options being considered for the treatment of SCC. This review summarizes the current guidelines for treating low-risk and high-risk SCC and discusses rare, experimental, and anecdotal non-surgical treatments for SCC in the literature.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

Mycophenolate mofetil inhibits Merkel cell carcinoma growth.

The direct antitumour effects of mTOR inhibitors against cutaneous squamous cell carcinoma (SCC) have prompted a paradigm shift towards using sirolimus for allograft rejection prophylaxis in patients with high-risk SCC who have had a solid organ transplant (SOT). Patients who have had an SOT are at higher risk for Merkel cell carcinoma (MCC), yet there is little evidence concerning potential antitumour effects of immunosuppressive drugs against MCC. Screening seven immunosuppressive drugs in six MCC cell lines revealed that mycophenolate mofetil (MMF) had strong antitumour activity (surpassing mTOR inhibitors) and higher potency in MCC vs. other cancer types. MMF also inhibited MCC tumour growth in mice. Our preclinical findings strongly suggest the utility of MMF in patients with MCC who require immunosuppression.

Epidermolysis-Bullosa-Associated Squamous Cell Carcinomas Support an Immunosuppressive Tumor Microenvironment: Prospects for Immunotherapy.

Cutaneous squamous cell carcinomas (SCCs) are a major complication of some subtypes of epidermolysis bullosa (EB), with high morbidity and mortality rates and unmet therapeutic needs. The high rate of endogenous mutations and the fibrotic stroma are considered to contribute to the pathogenesis. Patients with dystrophic EB (DEB) and Kindler EB (KEB) have the highest propensity for developing SCCs. Another patient group that develops high-risk SCCs is immunosuppressed (IS) patients, especially after organ transplantation. Herein, we interrogate whether immune checkpoint proteins and immunosuppressive enzymes are dysregulated in EB-associated SCCs as an immune resistance mechanism and compare the expression patterns with those in SCCs from IS patients, who frequently develop high-risk tumors and sporadic SCCs, and immunocompetent (IC) individuals. The expression of indoleamine 2,3-dioxygenase (IDO), programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), T cell immunoglobulin and mucin-domain-containing protein-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and inflammatory infiltrates (CD4, CD8, and CD68) was assessed via immunohistochemistry and semi-quantitative analysis in 30 DEB-SCCs, 22 KEB-SCCs, 106 IS-SCCs, and 100 sporadic IC-SCCs. DEB-SCCs expressed significantly higher levels of IDO and PD-L1 in tumor cells and PD-1 in the tumor microenvironment (TME) compared with SCCs from IC and IS individuals. The number of CD4-positive T cells per mm2 was significantly lower in DEB-SCCs compared with IC-SCCs. KEB-SCCs showed the lowest expression of the exhaustion markers TIM-3 and LAG-3 compared with all other groups. These findings identify IDO, PD-1, and PD-L1 to be increased in EB-SCCs and candidate targets for combinatory treatments, especially in DEB-SCCs.

Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos

BackgroundThe COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. ObjectiveTo compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methodsWe conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. ConclusionsAlthough there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Efficacy of micrographic surgery versus conventional excision in reducing recurrence for basal cell carcinoma and squamous cell carcinoma: A systematic review and meta-analysis.

The standard of care for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) involves excision by conventional surgery (CS) with a predefined safety margin of resection or micrographic surgery (MS) with microscopic margin control. Previous studies have reported the superiority of MS in reducing recurrences for high-risk BCC and SCC. This systematic review aimed to assess MS and CS recurrence rates by including randomized clinical trials (RCTs) and cohort studies. A systematic review and meta-analysis were conducted for related studies in PubMed, LILACS, Embase, Scopus, Web of Science, CINHAL and Cochrane until May 2023. RCTs and cohorts involving patients with BCC or SCC submitted to MS and CS were included. Risk of bias assessment followed Cochrane-recommended tools for RCTs and cohorts, and certainty of evidence followed the GRADE approach. Pooled estimates were used to determine the relative risk (RR) and absolute risk difference (RD) using a random-effects model. Seventeen studies were included, two RCTs and fifteen cohorts. There were 82 recurrences in 3050 tumours submitted to MS, with an overall recurrence rate of 3.1% (95% CI 2.0%-4.7%). For CS, there were 209 recurrences in 3453 tumours, with a recurrence rate of 5.3% (95% CI 2.9%-9.3%). The combined estimate of RR was 0.48 (95% CI 0.36-0.63), without heterogeneity nor evidence of publication bias (p > 0.3). The RD resulted in 2.9% (95% CI 1.0%-4.9%; NNT = 35). Regarding subgroup analysis, the RR for BBC was 0.37 (95% CI 0.25-0.54), and RD was 3.7% (95% CI 0.8%-6.5%; NNT = 28). For SCC, RR was 0.57 (95% CI 0.29-1.13), and RD was 1.9% (95% CI 0.8%-4.7%; NNT = 53). Among primary tumours, RR was 0.39 (95% CI 0.28-0.54), and for recurrent tumours was 0.67 (95% CI 0.30-1.50). There is moderate evidence based on two RCTs, and low evidence based on 15 cohort studies that MS is superior to CS in reducing recurrences of BCCs and primary tumours. The development of protocols that maximize the cost-effectiveness of each method in different clinical scenarios is paramount.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors

BackgroundThe COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. ObjectiveTo compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methodsWe conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. ConclusionsAlthough there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Limitation of PET/CT for screening of synchronous upper gastrointestinal cancer in oral cancer patients

ObjectivePatients with squamous cell carcinoma (SCC) of the head and neck including the oral cavity have a high risk of upper gastrointestinal cancer, especially esophageal cancer. Synchronous upper gastrointestinal cancers affect the field of radiation or surgery, and undetected double cancer can cause poor prognosis. The purpose of this retrospective study was to evaluate the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for detecting synchronous upper gastrointestinal cancer at the initial staging of oral cancer patients. MethodsBetween September 2006 and August 2021, 804 newly diagnosed oral squamous cell carcinoma patients who undergo esophagogastroduodenoscopy (EGD) and FDG-PET/CT at the initial staging were enrolled in this study. The incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was retrospectively calculated. Furthermore, we evaluated the diagnostic performance of FDG-PET/CT for screening of synchronous upper gastrointestinal cancer in oral cancer patients. ResultsThe incidence of synchronous upper gastrointestinal cancer in EGD screening at the initial staging of oral cancer was 4.2% (34/804 patients). Of 34 oral cancer patients with synchronous upper gastrointestinal cancer, 26 (76.5%) had both smoking and drinking habits. The sensitivity, specificity, accuracy, false-negative rate, false-positive rate, positive predictive value, and negative predictive value of FDG-PET/CT for synchronous upper gastrointestinal cancer were 44.1%, 99.6%, 97.3%, 55.9%, 0.4%, 83.3%, and 97.6%, respectively. ConclusionsBecause PET/CT cannot sufficiently detect synchronous upper gastrointestinal cancer in oral SCC patients, EGD screening before the treatment may be suitable for the high-risk oral SCC patients.

Oral cancer in Australia: Rising incidence and worsening mortality.

Oral cancer, predominantly squamous cell carcinoma (SCC), is a lethal and deforming disease of rising incidence. Although largely preventable by eliminating harmful tobacco and alcohol risk factor behaviour, 5-year survival rates remain around 50%, primarily due to late presentation of advanced stage disease. Whilst low socio-economic status, regional and remote location and indigenous status are associated with head and neck cancer in general, detailed incidence and demographic data for oral SCC in Australia are limited. This study aimed to characterise the Queensland population at risk of oral SCC development. Following ethical approval, the Queensland Cancer Register (QCR) dataset was analysed to determine patterns of incidence, anonymised patient demographics, clinical presentation and outcome data for oral SCC cases diagnosed between 1982 and 2018. Data from 9887 patients were obtained. Mean age at diagnosis was 64.55 years, with a male-to-female ratio of 2.51:1; males were diagnosed at a younger age (p < 0.001). At study census date, 59% of patients had died, with females demonstrating longer mean survival (p < 0.001). Clinicopathological data confirmed that SCC most commonly arose from tongue sites (49%) and, whilst tumours were predominantly moderately differentiated in nature (63%), patients with poorly differentiated carcinomas exhibited shortest survival times (p < 0.05). Over the 36-year study period, the number of diagnoses increased 4.49-fold, whilst the number of deaths increased 19.14-fold. Oral SCC poses a significant and growing healthcare problem in Queensland. In the absence of national screening, characterising the high-risk oral SCC population facilitates pragmatic opportunities to raise disease awareness, to deliver targeted screening and effective primary prevention strategies, and to provide early interventional treatment intervention to reduce disease mortality and morbidity.

A Rare Axillary Cutaneous Squamous Cell Carcinoma: A Case Report and Literature Review

Background: Non-melanoma skin cancer is the most frequent tumor in Brazil and the world. One of its forms, squamous cell carcinoma (SCC) predominantly affects the old white population in areas of high exposure to the sun. Most SCCs are indolent, evolving with a cure rate higher than 90% within five years. Rarely, metastasis occurs mainly in regional lymph nodes, but it can also happen in the lungs, liver, brain, skin, and bones. There are currently many treatment options; based on the stratification of the neoplasm as high or low risk, an appropriate approach is defined. Case presentation: This report presents the case of a patient with high-risk squamous cell carcinoma affecting an area not exposed to solar radiation and without any other previous triggering factor, which is quite uncommon for this type of tumor. The rarity of the case stems from the lack of scientific reports on the occurrence of SCC in the axillary region, without a history of local chronic inflammatory lesions. The Portuguese, English, and Spanish languages were used to search the database of the main scientific platforms Pubmed, Cochrane Library, Scielo, and Lilacs, with no results similar to the case reported. Conclusion: Despite the fact that the axillary area is not sun-exposed, squamous cell skin cancer manifested as an extensive lesion that required a complex surgical resection with flap repair. Such findings highlight the importance of a thorough physical exam and work-up to diagnose lesions in their early forms which require simple resection procedures and avoid late diagnoses resulting in complex procedures. Such an approach reduces the risk of various complications like wound infection or dehiscence, flap ischemia, or necrosis, among others.

Posterior Auricular Myiasis: Rare Presentation of a Malignant Lesion

Squamous cell carcinoma (SCC) arises from the malignant proliferation of the keratinocytes of the epidermis that has invaded into the dermis or beyond. Posterior auricular SCC is categorized as high-risk SCC. Infestation of fly larvae or maggots in living tissue of humans and other vertebrate animals is known as myiasis. Rarity of the site of involvement with an underlying malignancy is the peculiarity of this case report. We present a case of elderly male with a posterior auricular mass with myiasis, which turns out to be SCC. Early detection and combined modality of aggressive treatment with surgery and radiation improves the overall patient survival rate.

Abstract CT182: Phase I trials of personalized cancer vaccine TG4050 in surgically treated high-risk head and neck squamous cell carcinoma (HNSCC) and relapsing ovarian cancer (OvC) patients

Abstract Background: Cancer mutations acquired during carcinogenesis are not subject to central tolerance and thus, are cornerstone in cancer immunosurveillance. The use of mutation-derived neoepitopes to design cancer vaccines is an unprecedented opportunity to target efficient antigens, but the stochastic occurrence of mutations implies that a tailored vaccine needs to be designed and manufactured for each patient. We used next generation sequencing, machine learning based genomic data analysis and advances in genome editing to systematically identify private neoepitopes in high-risk HPV negative HNSCC and relapsing OvC patients. Methods: Mutations were identified by DNA and RNA sequencing and putative epitopes were selected for vaccine design on their likelihood to elicit a class I or II response based on HLA binding, allelic frequency, prediction of processing and expression at RNA level. The vaccine was a recombinant virus of the modified Vaccinia Ankara (MVA) strain encoding for up to 30 sequences of 29 amino acids centred on the predicted epitope and flanked with the normal germline sequence in case of missense mutations, and of the mutated protein sequence in case of frameshift mutations. The viral vaccine was amplified under GMP conditions and administered to patients after curative intent treatment in two phase I trials. Treatment was started for OvC patients at relapse defined as elevation of CA-125 or onset of suspicious radiological findings and, after first line therapy for HNSCC patients with locally advanced disease with either extracapsular extension or positive resection margins following upfront surgery. The vaccine was administered for 6 weeks and a booster dose every three weeks over a year, in absence of other cancer therapy. Results: Six patients (4 OvC and 2 HNSCC) were treated and experienced only mild related adverse events. After 6 doses of vaccine, we measured immunoreactive T cells in PBMCs against each of the targeted epitopes using an ex vivo IFNγ ELISPOT showed robust responses in all evaluable patients. Positive responses to vaccination were observed for a total of 46 epitopes over 115 tested with a median of 11 epitopes (6 to 18) per patient. Responses were directed against both class I and II epitopes and were either de novo responses (64%) or amplification of pre-existing responses (36%). In parallel, phenotyping of patient PBMCs showed, in all treated patients, a decline in naïve CD4 and CD8 cells and the onset of effector CD27- CD4 and CD27-/CD57+ CD8; similarly, CD56dim NK cells increased suggesting a stimulation of antitumor innate immunity. In one ovarian cancer patient, these immune changes correlated with a normalization of CA-125 that lasted 7 months. Conclusions: These data show that the personalized approach with TG4050 is feasible, safe and immunogenic. The two phase I trials are ongoing. Citation Format: Matthew S. Block, Jean-Pierre Delord, Christian H. Ottensmeier, Christophe Le Tourneau, Ana Lalanne, Olivier Lantz, Keith L. Knutson, Gisèle Lacoste, Annette Tavernaro, Maud Brandely, Nathalie Silvestre, Benoit Grellier, Yoshiko Yamashita, Onoue Kousuke, Naoko Yamagata, Eric Quemeneur, Kaidre Bendjama. Phase I trials of personalized cancer vaccine TG4050 in surgically treated high-risk head and neck squamous cell carcinoma (HNSCC) and relapsing ovarian cancer (OvC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT182.

Assessment of the Diagnostic Accuracy of Baseline Clinical Examination and Ultrasonographic Imaging for the Detection of Lymph Node Metastasis in Patients With High-risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Patients with cutaneous squamous cell carcinoma (SCC) of the head and neck may develop lymph node metastasis; therefore, additional workup of the regional lymph nodes in these patients should be considered. However, there is uncertainty regarding the value of baseline ultrasonographic imaging in addition to clinical examination for the detection of metastasis. To assess the diagnostic accuracy of clinical examination and baseline ultrasonography for the detection of metastasis among patients with high-risk cutaneous SCC of the head and neck and to assess the accuracy of ultrasonography when baseline clinical examination produces negative results. This diagnostic study was conducted among a retrospective cohort of 233 patients with 246 high-risk cutaneous SCC tumors of the head and neck. The study included all patients with high-risk cutaneous SCC of the head and neck who received clinical examination and baseline ultrasonographic imaging of their lymph nodes at the Erasmus Medical Center Cancer Institute, a tertiary referral hospital for patients with skin cancer in Rotterdam, the Netherlands, between January 1, 2015, and December 31, 2017. Data were analyzed from October 13, 2020, to September 29, 2021. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Fine-needle aspiration cytologic biopsy and 6 months of follow-up per patient were used as the reference standards. Among 233 patients (176 men [75.5%]; median age, 79.1 years [IQR, 71.5-83.7 years]; data on race and ethnicity were not collected) with 246 high-risk cutaneous SCC tumors of the head and neck, 20 metastases were cytologically confirmed at baseline, and 2 metastases were detected during 6 months of follow-up, yielding a 9% metastasis rate. The sensitivity of clinical examination was 50% (95% CI, 28%-72%), and the specificity was 96% (95% CI, 93%-98%). The PPV and NPV were 55% (95% CI, 36%-72%) and 95% (95% CI, 93%-97%), respectively. In the total cohort, ultrasonography had a sensitivity of 91% (95% CI, 71%-99%) and a specificity of 78% (95% CI, 72%-83%), with a PPV of 29% (95% CI, 23%-35%) and an NPV of 99% (95% CI, 96%-100%). In the group of patients with negative results at baseline clinical examination, 9 of 11 metastases were detected by ultrasonography, with 82% sensitivity (95% CI, 48%-98%); specificity was 79% (95% CI, 73%-84%), PPV was 17% (95% CI, 12%-23%), and NPV was 99% (95% CI, 96%-100%). In this diagnostic study, among a cohort of patients with high-risk cutaneous SCC of the head and neck, baseline ultrasonography was more sensitive than clinical examination alone for the detection of lymph node metastasis. In the setting of a negative result at baseline clinical examination, ultrasonography had high sensitivity for detecting nodal metastases, but this sensitivity should be evaluated against the high rate of false-positive findings.

Comprehensive multiomic characterization of human papillomavirus-driven recurrent respiratory papillomatosis reveals distinct molecular subtypes

Recurrent respiratory papillomatosis (RRP) is a debilitating neoplastic disorder of the upper aerodigestive tract caused by chronic infection with low-risk human papillomavirus types 6 or 11. Patients with severe RRP can require hundreds of lifetime surgeries to control their disease and pulmonary papillomatosis can be fatal. Here we report the comprehensive genomic and transcriptomic characterization of respiratory papillomas. We discovered and characterized distinct subtypes with transcriptional resemblance to either a basal or differentiated cell state that associate with disease aggressiveness and differ in key molecular, immune and APOBEC mutagenesis profiles. Through integrated comparison with high-risk HPV-associated head and neck squamous cell carcinoma, our analysis revealed divergent molecular and immune papilloma subtypes that form independent of underlying genomic alterations. Cumulatively our results support the development of dysregulated cellular proliferation and suppressed anti-viral immunity through distinct programs of squamous cell differentiation and associated expression of low-risk HPV genes. These analyses provide insight into the pathogenesis of respiratory papillomas and provide a foundation for the development of therapeutic strategies.

Prognostic Gene Signature for Squamous Cell Carcinoma with a Higher Risk for Treatment Failure and Accelerated MEK-ERK Pathway Activity.

Simple SummarySquamous cell carcinoma (SCC) is the most prevalent type of human cancer worldwide and represents the majority of head and neck tumors. As SCC from aerodigestive or genitourinary tracts share not only common etiology and histological features but also molecular patterns, the major objectives of this study were the establishment of a pan-SCC-related prognostic gene signature by an integrative analysis of multi-omics data and the elucidation of underlying oncogenic pathway activities as potential vulnerabilities for a more efficient and less toxic therapy. Our approach delivers a reliable molecular classifier to identify HNSCC and other SCC patients at higher risk for treatment failure with tumors characterized by a more prominent MAPK activity, who might benefit from a targeted treatment with MEK inhibitors.Squamous cell carcinoma (SCC) is the most prevalent histological type of human cancer, including head and neck squamous cell carcinoma (HNSCC). However, reliable prognostic gene signatures for SCC and underlying genetic and/or epigenetic principles are still unclear. We identified 37 prognostic candidate genes by best cutoff computation based on survival in a pan-SCC cohort (n = 1334) of The Cancer Genome Atlas (TCGA), whose expression stratified not only the pan-SCC cohort but also independent HNSCC validation cohorts into three distinct prognostic subgroups. The most relevant prognostic genes were prioritized by a Least Absolute Shrinkage and Selection Operator Cox regression model and were used to identify subgroups with high or low risks for unfavorable survival. An integrative analysis of multi-omics data identified FN1, SEMA3A, CDH2, FBN1, COL5A1, and ADAM12 as key nodes in a regulatory network related to the prognostic phenotype. An in-silico drug screen predicted two MEK inhibitors (Trametinib and Selumetinib) as effective compounds for high-risk SCC based on the Cancer Cell Line Encyclopedia, which is supported by a higher p-MEK1/2 immunohistochemical staining of high-risk HNSCC. In conclusion, our data identified a molecular classifier for high-risk HNSCC as well as other SCC patients, who might benefit from treatment with MEK inhibitors.

A study of the effects of delayed patient presentation on cutaneous SCC progression

A cohort study of patients, who underwent cutaneous squamous cell carcinoma (SCC) excision, was undertaken to evaluate the effects of the COVID-19 pandemic on treatment times and histopathological features. We identified all patients who had SCCs excised in October 2020 (pandemic group); the control group included all patients who underwent excision of SCCs during October 2019 (pre-pandemic group). Collected data included SCC subtype, thickness, size, clearance margins, referral details, patient comorbidities and operative data. There were 140 patients (174 SCCs; pre-pandemic group=74; pandemic group=100) identified for study inclusion. Both groups were well matched for age, sex, previous history of cancer, cutaneous SCC and histological subtype. There was a delay in median patient presentation time to the GP in the pandemic versus pre-pandemic group (106 days vs. 56 days, p <0.001); this led to a longer overall time to surgery (167 days vs. 110.5 days, p<0.001). Pandemic group SCCs had larger median Breslow depths (4mm vs. 3mm, p=0.01), a greater proportion of Clark's level 4 and 5 lesions (76.9% vs. 61.1%, p=0.03), and a higher rate of high (20-40mm) and very high (>40mm) risk SCCs as defined by British Association of Dermatology diameter criteria (56.1% vs. 39.2%, p=0.03), versus the pre-pandemic group. There was a 57-day median SCC treatment delay, and an associated development of higher risk SCCs by the time of surgery. Despite the challenges of a pandemic, patients should seek early consultation for suspicious skin changes, and healthcare systems should maintain skin cancer treatment pathways.

New Developments in the Management of Cutaneous Squamous Cell Carcinoma.

After studying this article, the participant should be able to: 1. List important prognostic features that affect cutaneous squamous cell carcinoma risk. 2. Summarize the changes to the AJCC Cancer Staging Manual, Eighth Edition, staging system for cutaneous squamous cell carcinoma. 3. Evaluate the draining nodal basin with appropriate imaging modalities. 4. Recommend adjuvant radiation therapy in the correct clinical setting for high-risk tumors. 5. Recognize the currently available treatments for advanced cutaneous squamous cell carcinoma. This continuing medical education article reviews the features, management, and prognosis of cutaneous squamous cell carcinoma with an emphasis on high-risk squamous cell carcinoma and data from the past 3 years. This review will discuss the primary tumor management, high-risk features of a squamous cell carcinoma, changes to the American Joint Committee on Cancer staging system, and the utility of sentinel lymph node biopsy, and critically review the evidence regarding adjuvant therapy.

The incidence and clinical analysis of non-melanoma skin cancer

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.

Transcriptome array screening and verification of oral leukoplakia carcinogenesis-related hypoxia-responsive gene and microRNA.

To study the hypoxia response gene and microRNA (miRNA) expression profiles in the pathogenesis and progression of oral leukoplakia (OLK). Affymetrix GeneChip human transcriptome array 2.0 was used to detect the transcriptome of normal mucosa, low-risk OLK, high-risk OLK, and early squamous cell carcinoma (SCC). Gene ontology function analysis was used to screen genes and key miRNAs whose biological role is hypoxia response. Quantitative reverse transcription polymerase ch-ain reaction (qRT-PCR) was used to verify the expression of hypoxia response genes and miRNAs. A total of 7 different genes of hypoxia response between normal mucosa and low-risk OLK, 10 genes between low-risk and high-risk OLK, and 21 genes between high-risk OLK and SCC were identified. The results of qRT-PCR showed that the expression of hypoxia-inducible factor 1α, chemokine cc-motif ligand 2, and matrix metalloproteinase 3 mRNA and miR-21 in normal mucosa, OLK, and SCC increased in a stepwise manner. The expression difference between OLK and SCC was statistically significant and consistent with the results of transcriptome array. The hypoxia response gene and related miRNA play roles in the development and progression of OLK.