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AbstractBackground & AimMethods & MaterialsResultsConclusionRecent advancements in analytical techniques have highlighted the potential of Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy as a quick, cost-effective, non-invasive, and efficient tool for cancer diagnosis. This study aims to evaluate the effectiveness of ATR-FTIR spectroscopy in combination with supervised machine learning classification models for diagnosing OSCC using saliva samples.Eighty unstimulated whole saliva samples from OSCC patients and healthy controls were collected. The ATR-FTIR spectroscopy was performed and spectral data were used to classify healthy and OSCC groups. The data were analyzed using machine learning classification methods such as Partial Least Squares-Discriminant Analysis (PLS-DA) and Support Vector Machine Classification (SVM-C). The classification performance of the models was evaluated by computing sensitivity, specificity, precision, and accuracy.The samples were classified into two classes based on their spectral data. The obtained results demonstrate a high level of accuracy in the prediction sets of the PLS-DA and SVM-C models, with accuracy values of 0.960 and 0.962, respectively. The OSCC group sensitivity values for both PLS-DA and SVM-C models was 1.00, respectively.The study indicates that ATR-FTIR spectroscopy, combined with chemometrics, is a potential method for the non-invasive diagnosis of OSCC using saliva samples. This method achieved high accuracy and the findings of this study suggest that ATR-FTIR spectroscopy could be further developed for clinical applications in OSCC diagnosis. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMaterial and methodsResultsConclusionSquamous cell carcinoma (SCC) of the temporal bone (TB) is a rare pathology originating from the external auditory canal (EAC). Surgery remains the gold standard to achieve local control.Aims/Objectives:The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) after surgery of the SCC of EAC.A retrospective chart review in a tertiary referral center included 26 patients: 23 were operated with lateral temporal bone resection (LTBR, n = 10) and extended temporal bone resection (ETBR, n = 13). The outcomes were OS and DFS.Adjuvant radiotherapy was performed in 91.3% (n = 21/23). Mean age was 60.8 and sex ratio was 1. Median follow-up was 43 months; The 5-years OS was 90% (± 9.5%) and 47.7% (± 12.9%) for stage I/II and III/IV respectively (p = .033). DFS was 67.6% (IC 95%, 51.4%–88.9%) without statistical difference between early advanced stage. Incomplete margins (p = .004) and Stage IV(p < .001) were associated with poorer DFS. Free margins significantly correlated with better OS (HR = 9.8, p = .04).En bloc surgical resection with free margins, coupled with postoperative radiotherapy, provides optimal local control. For stage IV tumors, where complete margins are achievable, ETBR is recommended to enhance local control. [ABSTRACT FROM AUTHOR]

Lip and oral cavity SCC account for 2nd highest incidence of cancers and 3rd most common cause of mortality from cancer in India. Reconstruction of defects of central arch invading cancers results in poor cosmetic and functional outcomes if free flaps are not used. 30 patients with Oral SCC in the age group 20–75 years requiring central arch segmental mandibulectomy were included. Reconstruction was done with pedicled bipaddled PMMC flap with 'AJ's orbicularis oris stitch' using Fiber wire. Patients were divided into 4 groups according to extent of lip and skin loss post excision of primary tumour. Patients were evaluated with subjective scores for drooling, oral competence and cosmesis. There were 4, 12, 9 and 5 patients in Group A, B, C and D respectively. Mean subjective scores using our technique for drooling, oral competence and cosmesis were 3.75/4,3.75/4 and 3.5/4 for group A, 3.45/4, 3.36/4 and 3.09/4 for group B, 2.8/4, 2.6/4 and 2.3/4 for group C defects and 2.5/4, 3/4 and 2.5/4 for group D defects respectively. Over all scores for all patients were 3.2/4, 3.14/4 and 2.84/4 for drooling, oral competence and cosmesis. This simple, quick and inexpensive technique of reconstruction of central mandibular arch defects can drastically improve cosmetic and functional outcomes in a resource restrained set up. However, long term results and comparison studies are required for standardisation of the technique. [ABSTRACT FROM AUTHOR]

Multidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance. [ABSTRACT FROM AUTHOR]

The most dangerous disease in recent decades is lung cancer. The most accurate method of cancer diagnosis, according to research, is through the use of histopathological images that are acquired by a biopsy. Deep learning techniques have achieved success in bioinformatics, particularly medical imaging. In this paper, we present an innovative method for rapidly identifying and classifying histopathology images of lung tissues by combining a newly proposed Convolutional Neural Networks (CNN) model with a few total parameters and the enhanced Light Gradient Boosting Model (LightGBM) classifier. After the images have been pre-processed in this study, the proposed CNN technique is provided for feature extraction. Then, the LightGBM model with multiple threads has been used for lung tissue classification. The simulation result, applied to the LC25000 dataset, demonstrated that the novel technique successfully classifies lung tissue with 99.6% accuracy and sensitivity. Furthermore, the proposed CNN model has achieved the lowest training parameters of only one million parameters, and it has also achieved the shortest processing time of just one second throughout the feature extraction process. When this result is compared with the most recent state-of-the-art approaches, the suggested approach has increased effectiveness in the areas of both disease classification accuracy and processing time. [ABSTRACT FROM AUTHOR]

Advanced cutaneous squamous cell carcinoma (cSCC) can be a life-threatening disease for which effective and safe treatment in advanced stages is very limited. GP-2250 has been recently proven to have—in vitro and in vivo—antineoplastic effects on cancer cells. This study aims to investigate the potential anti-neoplastic effects of GP-2250 on the cSCC cell lines SCC13 and A431 through dose finding assessments, MTT cytotoxicity assays, cell migration assays, BrdU proliferation assays and FCM analysis. Our preliminary results have shown for the first time evidence for anti-neoplastic effects of GP-2250 on cSCC cells, enhancing cytotoxicity, attenuating cancer cell proliferation, inducing apoptosis and reducing tumour cell migration. Further investigations evaluating the modes of action of GP-2250 on cSCC cell lines are warranted in order to justify the use in vivo studies.

BACKGROUND: This review aims to determine the potential role of Merkel Cell Polyomavirus (MCPyV) in the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. METHODS: A PRISMA systematic search appraisal was conducted. The Scopus, Web of Science, PubMed, EMBASE, Google Scholar, and MEDLINE databases for publications in English were searched up to September 2022 for all relevant articles. All articles that have outlined the contributions of the MCPyV to cervical squamous cell carcinomas and adenocarcinomas were included. RESULTS: The six databases produced 6806 articles. Only six articles met the inclusion criteria and were included. The protocol of this review was submitted and registered with the PROSPERO (Code no. CRD42022369197). The total sample size across the articles was 1135; the age of the participants ranged between 18 and 75 years. In addition, the included articles were conducted between 2012 to 2016. All included articles have a cross-sectional design. Furthermore, different kinds of samples were collected in the reviewed articles, namely cervical tissue biopsies, cervical smears, formalin-fixed paraffin-embedded resection specimens, and cervical adenocarcinomas. Moreover, five articles showed no statistically significant association between the MCPyV and cervical squamous cell carcinomas and adenocarcinomas. In contrast, one article revealed a positive association between MCPyV and cervical squamous cell carcinomas and adenocarcinomas. CONCLUSIONS: MCPyV could not be associated with the pathogenesis of cervical squamous cell carcinomas and adenocarcinomas. Further attention should be given to examining this association, and further studies with a large sample size are recommended to confirm these findings. [ABSTRACT FROM AUTHOR]

Oropharyngeal squamous cell carcinomas (OPSCC) represent a major public health challenge. In 2020, the international agency for research on cancer (IARC) recorded 98,421 cases of OPSCC worldwide. Over the past decade, the epidemiological profile of patients with OPSCC has shifted, mainly due to a change in etiological factors. Previously, alcohol and tobacco were considered the primary contributors, but the human papillomavirus (HPV) is now recognized as the leading cause of these tumors. This study aimed to conduct a literature review on the relationship between OPSCC and HPV for the general practitioner. The review examined the primary clinical differences between HPV+ and HPV- OPSCC, their prognosis and treatment. In addition, the various HPV diagnostic methods were analyzed. Although there is a vast amount of literature on HPV, this review is unique in its ability to present the key information in an organized and accessible way and enables healthcare professionals to gain a better understanding of the relationship between HPV and oropharyngeal cancer. This, in turn, can contribute to the prevention of various cancers caused by the HPV virus, including oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Xeroderma pigmentosum (XP) is a highly complex autosomal recessive disease linked to an enzymatic DNA repair disorder. Herein, we report the clinical and evolutionary aspects of XP in Niger. Materials and Methods: Our study included patients diagnosed with XP from two families. Results: We collected eight patients with an average age of 5.5 years, with extremes of two and thirteen years. The sex ratio was 1. Consanguinity was found in both families. The first tumor appeared between three and five years of age in six cases and around eight years of age in two cases. The tumors were cutaneous in seven cases, and extra-cutaneous in five cases. Histology made it possible to identify basal cell and squamous cell carcinomas without any case of melanoma. Five out of eight died between the age of eight and twelve years. Conclusion: Prevention through the reduction of new cases by genetic counseling and antenatal diagnosis in families at risk is necessary. [ABSTRACT FROM AUTHOR]

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1–92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1–77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed – a usually weak – CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p < 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p = 0.0295) and shortened recurrence‐free (p = 0.0094) and overall survival (p = 0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p = 0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors. [ABSTRACT FROM AUTHOR]

Oropharyngeal squamous cell carcinomas (OPSCC) represent a major public health challenge. In 2020, the international agency for research on cancer (IARC) recorded 98,421 cases of OPSCC worldwide. Over the past decade, the epidemiological profile of patients with OPSCC has shifted, mainly due to a change in etiological factors. Previously, alcohol and tobacco were considered the primary contributors, but the human papillomavirus (HPV) is now recognized as the leading cause of these tumors. This study aimed to conduct a literature review on the relationship between OPSCC and HPV for the general practitioner. The review examined the primary clinical differences between HPV+ and HPV− OPSCC, their prognosis and treatment. In addition, the various HPV diagnostic methods were analyzed. Although there is a vast amount of literature on HPV, this review is unique in its ability to present the key information in an organized and accessible way and enables healthcare professionals to gain a better understanding of the relationship between HPV and oropharyngeal cancer. This, in turn, can contribute to the prevention of various cancers caused by the HPV virus, including oropharyngeal cancer.

Abstract Background Primary parotid squamous cell carcinoma (SCC) is a rare entity with a poor prognosis. Pathologically, the diagnosis of it requires the exclusion of parotid mucoepidermoid carcinoma (MEC). Currently, the imaging features of primary parotid SCC and the predictive indicators for differential diagnosis of the two entities have not been well reported. Our purpose was to identify the imaging characteristics of primary parotid SCC and to determine the predictive factors for its’ differential diagnosis. Results Thirty-one participants with primary parotid SCC and 59 with primary parotid MEC were enrolled. Clinical, CT and MRI features were reviewed and compared by univariate analysis. Then, multinomial logistic regression was used to determine the predictors to distinguish parotid SCC from MEC. Most primary parotid SCCs exhibited irregular shape, ill-defined margin, incomplete or no capsule, heterogeneous and marked or moderate enhancement, necrosis, local tumor invasiveness (LTI). Age, maximal dimension, shape, degree of enhancement, gradual enhancement, necrosis, and LTI were different between the primary parotid SCCs and MECs in univariate analysis (p

The most dangerous disease in recent decades is lung cancer. The most accurate method of cancer diagnosis, according to research, is through the use of histopathological images that are acquired by a biopsy. Deep learning techniques have achieved success in bioinformatics, particularly medical imaging. In this paper, we present an innovative method for rapidly identifying and classifying histopathology images of lung tissues by combining a newly proposed Convolutional Neural Networks (CNN) model with a few total parameters and the enhanced Light Gradient Boosting Model (LightGBM) classifier. After the images have been pre-processed in this study, the proposed CNN technique is provided for feature extraction. Then, the LightGBM model with multiple threads has been used for lung tissue classification. The simulation result, applied to the LC25000 dataset, demonstrated that the novel technique successfully classifies lung tissue with 99.6% accuracy and sensitivity. Furthermore, the proposed CNN model has achieved the lowest training parameters of only one million parameters, and it has also achieved the shortest processing time of just one second throughout the feature extraction process. When this result is compared with the most recent state-of-the-art approaches, the suggested approach has increased effectiveness in the areas of both disease classification accuracy and processing time.

Objective: To investigate the effects of PD-1/PD-L1 inhibitor on regulatory T cells（Treg cells） and their subtypes in patients with lung squamous cell carcinoma. Methods: Newly diagnosed patients with lung squamous cell carcinoma admitted to our hospital from January 2019 to December 2020 were included in this study. All patients received Nivolumab, and were divided into remission group（n=20） and ineffective group（n=20） according to different therapeutic effects. Flow cytometry was used to detect the proportion of total Treg cells, PD-1+Treg cells, CD150+Treg cells, CTLA-4+Treg cells, and LAG-3+Treg cells in peripheral blood.Results: The proportions of total Treg cells, CTLA-4+Treg cells and LAG-3+Treg cells in the remission group were 4.052 ±0.231%,1.616 ±0.099% and 0.328 ±0.021%, respectively, and those in the ineffective group were 5.532 ±0.395%, 3.277 ±0.224% and 0.857 ±0.108%, respectively, the differences were statistically significant（t=3.239, P=0.009; t=6.776, P<0.001; t=4.807, P<0.001）. The proportions of PD-1+Treg cells and CD150+Treg cells in the remission group were 0.195±0.016% and 1.530±0.113%, respectively, and those in the ineffective group were 0.203±0.018% and 1.787±0.157%, respectively, with no statistically significant differences（t=0.318,P=0.757; t=1.329, P=0.214）. Conclusion: The proportions of total Treg cells, CTLA-4+Treg cells and LAG-3+Treg cells in peripheral blood of patients with lung squamous cell carcinoma who did not respond to PD-1/PD-L1 inhibitors were significantly increased. [ABSTRACT FROM AUTHOR]

Background: Primary parotid squamous cell carcinoma (SCC) is a rare entity with a poor prognosis. Pathologically, the diagnosis of it requires the exclusion of parotid mucoepidermoid carcinoma (MEC). Currently, the imaging features of primary parotid SCC and the predictive indicators for differential diagnosis of the two entities have not been well reported. Our purpose was to identify the imaging characteristics of primary parotid SCC and to determine the predictive factors for its' differential diagnosis. Results: Thirty-one participants with primary parotid SCC and 59 with primary parotid MEC were enrolled. Clinical, CT and MRI features were reviewed and compared by univariate analysis. Then, multinomial logistic regression was used to determine the predictors to distinguish parotid SCC from MEC. Most primary parotid SCCs exhibited irregular shape, ill-defined margin, incomplete or no capsule, heterogeneous and marked or moderate enhancement, necrosis, local tumor invasiveness (LTI). Age, maximal dimension, shape, degree of enhancement, gradual enhancement, necrosis, and LTI were different between the primary parotid SCCs and MECs in univariate analysis (p < 0.05). While in multinomial logistic regression analysis, only age and necrosis were the independent predictors for distinguishing parotid SCC from MEC, and this model exhibited an area under curve of 0.914 in ROC curve analysis. Conclusions: Primary parotid SCC has some distinct imaging features including the large tumor size, irregular shape, ill-defined margin, and particularly the marked central necrosis. Patients with age ≥ 51.5 years and necrosis on the image of the primary tumor in the parotid gland could be more likely to be SCCs than MECs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the differences of PD-L1 protein and related miRNA expression between lung squamous cell carcinoma and adenocarcinoma. Methods: From May 2019 to November 2020, newly treated patients with non-small cell lung cancer in our hospital were included in this study. According to the pathological types, the patients were divided into adenocarcinoma group and squamous cell carcinoma group. H&E staining was used to detect the number of immune cells. PD-L1, Ki-67, PD-1, CTLA-4 and LAG-3 expression was detected by immunohistochemistry. The differentially expressed miRNAs between squamous cell carcinoma and adenocarcinoma were screened by miRNA sequencing. Results: H&E staining results showed that the number of microenvironment immune cells in squamous cell carcinoma group was 86.86± 8.96/HPF, and that in adenocarcinoma group was 26.29± 3.99 /HPF (t=6.173, P<0.001). The positive expression rates of PD-1, CTLA-4 and LAG-3 in microenvironment immune cells of lung squamous cell carcinoma group were 53.71± 6.88%, 35.29± 3.25% and 34.43± 3.29%, respectively, and those of adenocarcinoma group were 22.29± 3.80%, 13.43± 2.32% and 24.00 ± 1.98% (t=3.997, P=0.002; t=5.476, P<0.001; t=2.719, P=0.019). The positive expression of PD-L1 protein was 76.67% in lung squamous cell carcinoma group and 36.67% in adenocarcinoma group (P=0.001). The expression of miRNAs associated with PD-L1 (miR-135, miR-24 and miR-30b, etc.) and PD-1 (miR-802, miR-155 and miR-3127-5p, etc.) in lung squamous cell carcinoma was significantly higher than that in adenocarcinoma. Conclusion: The expression of PD-L1 protein and related miRNA in lung squamous cell carcinoma, the positive proportion of PD-1, CTLA-4 and LAG-3 in microenvironment immune cells were significantly higher than those in adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract Objective Human papillomavirus (HPV) gained momentum as a potential etiological factor for many types of cancers. Therefore, the aim of this study was to assess the prevalence of HPV-16 infection among Sudanese patients diagnosed with Squamous Cell Carcinoma (SCC) and Salivary Gland Carcinoma. A descriptive, hospital-based study was conducted. 150 formalin-fixed paraffin-embedded blocks were collected. Results The study population included a total of 150 patients aged between 18 to 87 years with a mean age of 48.8 ± 11.9 years. Based on gender, females constituted 46.7% while males constituted 53.3%. The 150 patients were classified into 40 (26.0%) esophageal, 30 (20.0%) nasopharyngeal, 18 (12.0%) conjunctival, 18 (12.0%) tongue 12 (8.0%) laryngeal, 8 (5.3%) lip, 6 (4.0%) oropharyngeal, 6 (4.0%) mucoepidermoid, and 6 (4.0%) adenoid cystic, and 6 (4.0%) myoepithelial carcinomas. Odds ratio for male and female diagnosed with carcinoma was 1.025 [0.439–2.394, 95% CI]. Molecular detection of HPV-16 revealed a prevalence of 26 (17.3%) patients were positive for HPV-16. According to cancer diagnosis, esophageal SCC patients showed a high proportion of HPV-16; 14/40 (35.0%). A statistically significant difference was seen for the distribution of HPV-16 positive patients based on cancer diagnosis, P value 0.001.

Objective: Squamous cell carcinomas (SCCs) with shared etiology, histological characteristics, and certain risk factors represent the most common solid cancers. This study reports the crosstalk between autophagy and ferroptosis at the molecular level in SCCs, and their roles on the immunological tumor microenvironment (TME) of SCCs. Methods: In this study, the connections between autophagy and ferroptosis were characterized in SCCs by analyzing the associations between autophagy- and ferroptosis-related genes in mRNA expression and prognosis, protein-protein interactions and shared signaling pathways. Autophagy potential index (API) and ferroptosis potential index (FPI) of each tumor were quantified for reflecting autophagy and ferroptosis levels via principal-component analysis algorithm. Their synergistical roles on TME, immunity, drug resistance and survival were systematically analyzed in SCCs. Results: There were close connections between autophagy and ferroptosis at the mRNA and protein levels and prognosis. Both shared cancer-related pathways. The API and FPI were separately developed based on prognostic autophagy- and ferroptosis-related genes. A high correlation between API and FPI was found in SCCs. Their interplay was distinctly associated with favorable prognosis, enhanced sensitivity to chemotherapy drugs (Sunitinib, Gefitinib, Vinblastine and Vorinostat), an inflamed TME and higher likelihood of response to immunotherapy in SCCs. Conclusion: This study is the first to provide a comprehensive analysis of the interplay between autophagy and ferroptosis and their synergistical roles on manipulating the immunological TME in SCCs. These findings indicated that the induction of autophagy and ferroptosis combined with immunotherapy might produce synergistically enhanced anti-SCCs activity. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinomas are the second most frequent type of non-melanoma skin cancer. A 78-year-old man with a slow-growing but large nodular lesion on his scalp presented to the hospital. The nodular lesion was excised. Histologically, the lesion was diagnosed as a primary cutaneous myxoid spindle cell squamous cell carcinoma, which is the subject of this case report. Extracellular mucin production is an even less common finding in SCC. We also aim to discuss the histological and immunohistochemical findings for distinguishing MSC SCC from other primary cutaneous and metastatic spindle cell neoplasms with myxoid stroma.

Malignant tumors of the maxillofacial and oral region are relatively rare and form a very heterogeneous group of tumors whose incidence is constantly increasing. It is a disease of the elderly population, with a slight prevalence of males. The most common histological type is squamous cell carcinoma, and the most common localization of the tumor is on the skin and mucous membranes of this region. In the treatment of these tumors, the cooperation of different specialties is necessary. According to all modern recommendations for treatment, surgery is the first method of treatment, and radiotherapy has its place in both adjuvant and definitive approaches. Chemotherapy with limited effect is used for disseminated disease. The aim of the study was to present the role of radiotherapy in multidisciplinary treatment of malignant tumors of the oral and maxillofacial region.

ObjectiveSquamous cell carcinomas (SCCs) with shared etiology, histological characteristics, and certain risk factors represent the most common solid cancers. This study reports the crosstalk between autophagy and ferroptosis at the molecular level in SCCs, and their roles on the immunological tumor microenvironment (TME) of SCCs.MethodsIn this study, the connections between autophagy and ferroptosis were characterized in SCCs by analyzing the associations between autophagy- and ferroptosis-related genes in mRNA expression and prognosis, protein-protein interactions and shared signaling pathways. Autophagy potential index (API) and ferroptosis potential index (FPI) of each tumor were quantified for reflecting autophagy and ferroptosis levels via principal-component analysis algorithm. Their synergistical roles on TME, immunity, drug resistance and survival were systematically analyzed in SCCs.ResultsThere were close connections between autophagy and ferroptosis at the mRNA and protein levels and prognosis. Both shared cancer-related pathways. The API and FPI were separately developed based on prognostic autophagy- and ferroptosis-related genes. A high correlation between API and FPI was found in SCCs. Their interplay was distinctly associated with favorable prognosis, enhanced sensitivity to chemotherapy drugs (Sunitinib, Gefitinib, Vinblastine and Vorinostat), an inflamed TME and higher likelihood of response to immunotherapy in SCCs.ConclusionThis study is the first to provide a comprehensive analysis of the interplay between autophagy and ferroptosis and their synergistical roles on manipulating the immunological TME in SCCs. These findings indicated that the induction of autophagy and ferroptosis combined with immunotherapy might produce synergistically enhanced anti-SCCs activity.

BACKGROUND: Resistance to PD-1 blocking agents is not uncommon, limiting their wide clinical success. Certain tumor-infiltrating immune cells (e.g., TILs/CTLs) have emerged as biomarkers of response, and absence of such immune cells contributes to resistance. OBJECTIVE: We deconvoluted the dynamic immune microenvironment in a mouse model of oral carcinogenesis for augmenting the resistance to PD-1 blocking agents by combination. METHODS: Bioinformatics methods and routine biological experiments were adopted such as morphological analysis and ELISA in the 4NQO-treated mice model. RESULTS: Our findings revealed that dysplastic tongue tissues from 4NQO-treated mice were characterized by an immunosuppressive tumor microenvironment. Tongue tissues from mice treated with 4NQO for 12 weeks had higher levels of Th2 cells and Tregs compared to tissues taken from control mice or mice treated with 4NQO for 28 weeks; these results suggested a potential therapeutic benefit of anti-PD-1 in the oral cancer. The IL-17 pathway was significantly upregulated during progression from normal mucosa to hyperplasia and tumor formation in mice. Inhibition of IL-17 α combined with PD-1 blockade delayed the development of 4NQO-induced precancerous and cancerous lesions and prolonged the survival of 4NQO-treated mice. CONCLUSIONS: Our data suggested a strong rationale of IL-17 α blockade as a potential approach to augment the tumor-eliminating effects of anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Background MicroRNAs (miRNAs) are small nonprotein coding RNAs that play an important role in physiological cellular processes. MicroRNA (miR)-205 and miR-31 are among the most frequently altered miRNAs in human malignancies. Objective To measure miR-205 and miR-31 expression in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) skin biopsies in comparison with sun-exposed and nonexposed skin of healthy controls in order to evaluate their possible role in the pathogenesis. Patients and methods This study included 15 BCC patients, 15 SCC patients and 20 age-matched and sex-matched healthy controls (10 with biopsies from sun-exposed areas and 10 with biopsies from nonexposed areas). Skin biopsies were taken from all participants for assessment of miR-205 and miR-31 levels by real-time PCR. Results MiR-205 levels were significantly lower in BCC and in SCC than in controls, whether sun-exposed or nonexposed. MiR-31 levels were significantly higher in BCC and in SCC than in controls, whether sun-exposed or nonexposed. There was no significant relation between miR-205 or miR-31 and age, sex, duration, site, shape, or size in all groups. There was no significant correlation between miR-205 and miR-31 in BCC, SCC, sun-exposed controls or nonexposed controls. Conclusion The study revealed lower miR-205 and higher miR-31 levels in both BCC and SCC patients than in controls, suggesting a possible role for these miRNAs in the pathogenesis and management of BCC and SCC.

Objectives: To describe a large cohort of eyelid and periorbital SCCs, to compare the location of the tumor and of the pathological lymph nodes, and to analyze the risk factors for lymph node involvement among tumor characteristics., Methods: All patients managed inside our institution for an eyelid and periorbital SCCs were included. Tumor characteristics, imaging setup, excision margins, lymph node evolution features, local, regional, and distant recurrences rates, and global survival were reported. The risk for lymph node involvement and location of pathological lymph nodes were analyzed through univariate and multivariate analyses., Results: Between January 2012 and August 2022, 115 patients were included, and 18 presented a lymph node evolution (15.7%), involving the parotid gland in 16 cases (88.9%), the submental and submandibular areas in seven cases (38%), and the jugular and carotid areas in four cases (22%). Tumor size above 20 mm, infiltration of the external canthus and periorbital structures, the presence of perineural invasion or vascular embolism, the depth of infiltration, and the presence of a local recurrence were significantly associated with the risk of lymph node evolution., Conclusion: Periorbital and eyelid SCCs present a true potential for lymph node evolution especially through the parotid gland. Extension setup including the parotid gland and neck should be mandatory, and lymph node dissection should be associated in case of parotidectomy for lymph node involvement., Level of Evidence: IV Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs) develop in 15-30% of patients with BRAF(V600E) metastatic melanoma treated with BRAF inhibitors (BRAFi). These lesions resemble mouse skin tumors induced by the two-stage DMBA/TPA skin carcinogenesis protocol; in this protocol BRAFi accelerates tumor induction. Since prior studies demonstrated cyclooxygenase 2 (COX-2) is necessary for DMBA/TPA tumor induction, we hypothesized that COX-2 inhibition might prevent BRAFi-accelerated skin tumors. Celecoxib, a COX-2 inhibitor, significantly delayed tumor acceleration by the BRAFi inhibitor PLX7420 and decreased tumor number by 90%. Tumor gene expression profiling demonstrated that celecoxib partially reversed the PLX4720-induced gene signature. In PDV cuSCC cells, vemurafenib (a clinically approved BRAFi) increased ERK phosphorylation and soft agar colony formation; both responses were greatly decreased by celecoxib. In clinical trials trametinib, a MEK inhibitor (MEKi) increases BRAFi therapy efficacy in BRAF(V600E) melanomas and reduces BRAFi-induced KA and cuSCC frequency. Trametinib also reduced vemurafenib-induced PDV soft agar colonies, but less efficiently than celecoxib. The trametinb/celecoxib combination was more effective than either inhibitor alone. In conclusion, celecoxib suppressed both BRAFi-accelerated skin tumors and soft-agar colonies, warranting its testing as a chemopreventive agent for non-melanoma skin lesions in patients treated with BRAFi alone or in combination with MEKi.

Cutaneous squamous cell carcinomas are the second most frequent type of non-melanoma skin cancer. A 78-year-old man with a slow-growing but large nodular lesion on his scalp presented to the hospital. The nodular lesion was excised. Histologically, the lesion was diagnosed as a primary cutaneous myxoid spindle cell squamous cell carcinoma, which is the subject of this case report. Extracellular mucin production is an even less common finding in SCC. We also aim to discuss the histological and immunohistochemical findings for distinguishing MSC SCC from other primary cutaneous and metastatic spindle cell neoplasms with myxoid stroma. [ABSTRACT FROM AUTHOR]

The Hippo‐YAP pathway regulates organ size, tissue homeostasis, and tumorigenesis in mammals. In response to cell density, external mechanical pressure, and/or other stimuli, the Hippo core complex controls the translocation of YAP1/TAZ proteins to the nucleus and thereby regulates cell growth. Abnormal upregulation or nuclear localization of YAP1/TAZ occurs in many human malignancies and promotes their formation, progression, and metastasis. A key example is squamous cell carcinoma (SCC) genesis. Many risk factors and crucial signals associated with SCC development in various tissues accelerate YAP1/TAZ accumulation, and mice possessing constitutively activated YAP1/TAZ show immediate carcinoma in situ (CIS) formation in these tissues. Because CIS onset is so rapid in these mutants, we propose that many SCCs initiate and progress when YAP1 activity is sustained and exceeds a certain oncogenic threshold. In this review, we summarize the latest findings on the roles of YAP1/TAZ in several types of SCCs. We also discuss whether targeting aberrant YAP1/TAZ activation might be a promising strategy for SCC treatment. [ABSTRACT FROM AUTHOR]

Optical spectroscopy is studied to contribute to skin cancer diagnosis. Indeed, optical spectra are modified along cancer progression and provide complementary information (e.g., on metabolism and tissue structure) to clinical examination for surgical guidance [1,2]. The current original dataset is made of autofluorescence and diffuse reflectance spectra acquired in vivo on 131 patients' skin with the SpectroLive device [3,4]. Spatially-resolved spectroscopy measurements were performed using a multi-fiber optic probe featuring 4 distances (0.4-1 mm) between excitation and collection optical fibers: spatial resolution allows spectra acquired at different distances to carry information from different depths in skin tissues. Five types of autofluorescence spectra were acquired using five different wavelength excitations (on the 365-415 nm spectral range) in order to collect information on several skin endogenous fluorophores (e.g., flavins, collagen). A sixth light source (white broadband) was used to acquire diffuse reflectance spectra carrying information about skin scattering properties and skin endogenous absorbers such as melanin and hemoglobin. Patients were proposed to be included into the clinical trial if they were suspected of suffering from actinic keratoses (precancerous skin lesions) or from basal or squamous cell carcinomas: in all cases, complete diagnostics is provided in the dataset. To increase the interest of the dataset and evaluate the dependence of optical spectra (intensity, shape) not only on pathological states but also on healthy skin features (civil age, skin age, gender, phototype, anatomical site), spectra were acquired for all 131 patients on two so-called "reference" skin sites known to rarely suffer from skin cancer: palm of the hand (featuring a thick skin type) and inner wrist (featuring thin skin). Spectra are available in .tab files: first column displays the spectral range on which intensity spectra were recorded (317-788 nm) and each following column provides an intensity spectrum acquired by each spectrometer for a given combination of light source excitation and distance. Each of the 131 folders corresponding to each of the 131 patients contains a .json file providing patients clinical features: gender, civil age, skin age, phototype score and class. All .tab files names include anatomical site and anatomopathological diagnostics of the skin site on which spectra were acquired: codes were defined to match a letter or an acronym to each diagnostic and anatomical site. To ensure quality control, a spectrum was acquired on the same calibration standard before starting spectra acquisition on each patient. It is therefore possible to follow the impact of the acquisition optical chain ageing during the 4.5 years that the patients were included. This dataset can be used by epidemiologists for the characterization of populations affected by skin cancers (gender ratio, mean age, anatomical sites typically affected, etc.); it may also be used by researchers in artificial intelligence to develop innovative methods to process such data and contribute to non-invasive diagnostics of skin cancers whose incidence is steadily increasing., (© 2024 The Author(s).)

The Marjolin's ulcer (MU) is a rare malignant lesion, which is characterized by primary, chronic wound initially and formation of cancer after a certain incubation period eventually. Though few reports or a small case series about MU on the scalp have been published, special risk factors are still unknown about the formation of malignancy on the scalp with chronic ulcer. The aim of the article is to explore the risk factors. Seventy-four patients with the chronic ulcer were included in the study. In between, the chronic ulcer transformed into the MU on the scalp (tumor group) in 42 cases, while the chronic ulcer did not transform into the MU on the scalp (tumor-free group) in 32 cases as controlled group. We made a comparative study between the above two groups so as to find which risk factors were critical for cancer development. In tumor group, lymph node dissection was implemented if the lymph node metastasis was found. Artificial dura was used in eight cases when the dura was removed. Seven cases died. Two patients are currently undergoing follow-up. Other cases were without tumor detection from 1 to 7 years. When the comparative study between the above two groups, there is statistical significance about the influential factor: scar adherence to the skull (F = 5.602 P = .018). Scar adherence to the skull may be the most critical risk factor for cancer development for the scalp with chronic ulcer. [ABSTRACT FROM AUTHOR]

Giant squamous cell carcinomas (SCC) larger than 5 cm in diameter are uncommon; there is no guideline on the size of an SCC that is considered giant. Treatment may be difficult with the need for large tissue resections and complex surgical reconstruction. We report a rare case of giant squamous cell carcinoma of the shoulder attached to deep anatomic planes. The entire mass was removed, resulting in a large defect that was repaired with myocutaneous flap rotation of the latissimus dors. Three courses of radiotherapy were performed after surgery. Fifteen months after the operation, the patient is well and working without any local recurrence and metastasis.

The literature date estimated that about 5% of all oral cavity cancers are hard palate cancers while soft palate cancers account for about 5-12% of oropharyngeal cancers. Although rare, usually these tumors had a more aggressively behavior than other oral cancer sites. That is why our study aimed to investigate comparatively the epidemiological, clinical and histopathological peculiarities of the two palatal sites of oral squamous cell carcinomas. We conducted a retrospective study limited to a period of 10 years in a single medical institution to investigate the morphoclinical profile of such tumors. We found that patients with hard palate SCCs had an average age slightly larger compared to those who developed soft palate tumors. Also, those with hard palate tumors are mostly diagnosed in less advanced stages compared to those at the level of the soft palate, and implicitly the former had a longer survival time. Histopathologically the most encountered hard palate SCC were the conventional well-differentiated tumor, and from the peculiar SCC variant the papillary and verrucous forms while for the soft palate SCC prevailed the moderate and poor differentiated conventional SCC and from the peculiar SCC variant the basaloid and acantholytic forms. In conclusion hard palate tumors differ in many aspects from those of the soft palate, and thus specification of the origin tumor site become important for the assessment of prognosis, treatment and survival outcome of such patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC).Methods: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance.Results: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC.Conclusions: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS.Key Points: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G‐protein‐coupled receptor kinase‐2 (GRK2) expression is reduced in undifferentiated, high‐grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial‐to‐mesenchymal transition (EMT) phenotypic features, an EMT‐like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC. What's new? Head and neck squamous cell carcinoma (HNSCC) recurs in more than half of patients, with most ultimately dying from metastatic disease. In order to reverse this trend, a better understanding of molecular alterations that contribute to HNSCC is needed. Here, the authors identify a link between G‐protein‐coupled receptor kinase 2 (GRK2), a key signaling hub, and HNSCC, whereby high‐grade HNSCC tumors were found to exhibit atypically low GRK2 levels. Experiments in HNSCC cells further revealed that GRK2 silencing triggers epithelial‐to‐mesenchymal transition features, suggesting that GRK2 serves a key role in preserving the differentiated epithelial phenotype of squamous cells. [ABSTRACT FROM AUTHOR]

Background: EGFR, a member of the type 1 tyrosine kinase family of receptors, plays a crucial role in several types of cancer especially in squamous cell carcinoma of the head and neck (HNSCC). Objective: This study aims to determine the frequency of EGFR overexpression in HNSCC and to find a possible correlation with various clinical pathological parameters and patient outcomes. Materials and Methods: Fresh cancerous tissue samples and matched normal mucosa were collected from 78 previously untreated HNSCC patients after obtaining informed consent. All patients had no detectable distant metastases at presentation. EGFR mRNA expression was examined using quantitative real-time RT-PCR analysis. Data were correlated with both clinicopathological characteristics and survival outcome. Results: Overexpression of EGFR mRNA was found in 21 of 78 patients. EGFR expression was significantly correlated with lower overall survival. Conclusion: EGFR expression plays an important role in the pathogenesis and progression of HNSCC. [ABSTRACT FROM AUTHOR]

Giant squamous cell carcinomas (SCC) larger than 5 cm in diameter are uncommon; there is no guideline on the size of an SCC that is considered giant. Treatment may be difficult with the need for large tissue resections and complex surgical reconstruction. We report a rare case of giant squamous cell carcinoma of the shoulder attached to deep anatomic planes. The entire mass was removed, resulting in a large defect that was repaired with myocutaneous flap rotation of the latissimus dorsi. Three courses of radiotherapy were performed after surgery. Fifteen months after the operation, the patient is well and working without any local recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Rho GTPases are master regulators of actomyosin structure and dynamics and play pivotal roles in a variety of cellular processes including cell morphology, gene transcription, cell cycle progression and cell adhesion. The present study follows an observational study design employing computational tools. The source of patient's data was procured from the cBioportal database. This database hosts an exhaustive collection of patient's details from different cohorts. The aberrant expression of Rho GTPase is widely associated with human cancer, which is due to deletion/ addition or amplification of the gene. Gene expression profile and survival analysis was carried out using - UALCAN database. Gene alterations in the Rho GTPase family were identified using - cBioportal. Among 20 genes of the Rho family, five genes RAC2, RAC3, RHOF, RHOG and RHOH were found to exhibit a differential expression pattern with a statistically significant value less than 10-12. The effect of differential gene expression RHOG with different parameters such as grade, gender and race produced statistically significant value less than 0.05. Although, the gene alterations identified in Rho GTPase family genes did not correlate with the oncoprint data, which showed a maximum of 7% alteration in the RHOD gene, the expression pattern of other members of the family in HNSCC patients as documented in the study warrants further investigations to be carried out in these genes. [ABSTRACT FROM AUTHOR]

Laryngeal cancer accounts for one-third of all head and neck tumors, with squamous cell carcinoma (SCC) being the most predominant type, followed by neuroendocrine tumors. Chromogranins, are commonly used as biomarkers for neuroendocrine tumors, including laryngeal cancer. It has been reported that secretogranin VGF, a member of the chromogranin family, can be also used as a significant biomarker for neuroendocrine tumors. However, the expression and role of VGF in laryngeal carcinomas have not been previously investigated. Therefore, the present study aimed to determine the expression levels of VGF in laryngeal SCC (LSCC). The present study collected tumor tissues, as well as serum samples, from a cohort of 15 patients with LSCC. The results of reverse transcription-quantitative PCR, western blot analysis and immunofluorescence assays showed that the selective VGF precursor was downregulated in patients with LSCC. Notably, in tumor tissue, the immunoreactivity for VGF was found in vimentin-positive cells, probably corresponding to T lymphocytes. The current preliminary study suggested that the reduced expression levels of VGF observed in tumor tissue and at the systemic level could sustain LSCC phenotype. Overall, VGF could be a potential biomarker for detecting neoplastic lesions with a higher risk of tumor invasiveness, even in non-neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

Cervical lymph node metastasis affects the prognosis and overall survival rate of and therapeutic planning for patients with head and neck squamous cell carcinomas (HNSCCs). However, advanced diagnostic modalities still lack accuracy in detecting occult neck metastasis. A sentinel lymph node biopsy is a minimally invasive auxiliary method for assessing the presence of occult metastatic disease in a patient with a clinically negative neck. This technique increases the specificity of neck dissection and thus reduces morbidity among oral cancer patients. The removal of sentinel nodes and dissection of the levels between the primary tumour and the sentinel node or the irradiation of target nodal basins is favoured as a selective treatment approach; this technique has the potential to become the new standard of care for patients with HNSCCs. This article presents an update on clinical applications and novel developments in this field.

Background: Notch1 expression has been reported to be associated with chemotherapy resistance and poor prognosis, but the role of Notch1 in head and neck squamous cell carcinoma (HNSCC) sensitivity to anticancer drugs remains unclear. The aim of this study was to evaluate HNSCC sensitivity to paclitaxel and cisplatin in vitro and the chemotherapeutic response of HNSCC to these two drugs in vivo. Methods: We used immunohistochemistry to assess Notch1 expression in fresh HNSCC samples treated by PF (cisplatin+5- fluorouracil) and TPF (paclitaxel + cisplatin+5- fluorouracil). We also assessed the sensitivity of two HNSCC cell lines to the Notch1 inhibitor of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The overall and progression-free survival were assessed. Results: High Notch1 expression was significantly associated with paclitaxel resistance (P

Background: Mouth-dissolving wafer is polymer-based matrice that incorporates various pharmaceutical agents for oral drug delivery. This polymeric wafer is ingenious in the way that it needs not be administered with water, like in conventional tablet dosage form. It has better compliance among the pediatric and geriatric groups owing to its ease of administration., Objective: The polymeric wafer dissolves quickly in the oral cavity and is highly effective for a targeted local effect in buccal-specific ailments. It is a safe, effective, and versatile drug delivery carrier for a range of drugs used to treat a plethora of oral cavity-specific ailments that inflict common people, like thrush, canker sores, periodontal disease, benign oral cavity tumors, buccal neoplasm, and malignancies. This review paper focuses thoroughly on the present state of the art in mouth-dissolving wafer technology for buccal drug delivery and targeting. Moreover, we have also addressed present-time limitations associated with wafer technology to aid researchers in future developments in the arena of buccal drug delivery., Conclusion: This dynamic novel formulation has tremendous future implications for designing drug delivery systems to target pernicious ailments and diseases specific to the buccal mucosa. In a nutshell, this review paper aims to summarize the present state of the art in buccal targeted drug delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)