Squamous Cell Carcinoma Research Articles

MCRANet: MTSL-based connectivity region attention network for PD-L1 status segmentation in H&E stained images

The quantitative analysis of Programmed death-ligand 1 (PD-L1) via Immunohistochemical (IHC) plays a crucial role in guiding immunotherapy. However, IHC faces challenges, including high costs, time consumption and result variability. Conversely, Hematoxylin-Eosin (H&E) staining offers cost-effectiveness, speed, and stable results. Nonetheless, H&E staining, which solely visualizes cellular morphological features, lacks clinical applicability in detecting biomarker expressions like PD-L1. Substituting H&E staining for IHC in determining PD-L1 status is a clinically significant and challenging task. Motivated by above observations, we propose a Multi-Task supervised learning (MTSL)-based connectivity region attention network (MCRANet) for PD-L1 status segmentation in H&E stained images. To reduce interference from non-tumor areas, the MTSL-based region attention is proposed to enhances the network's capability to distinguish between tumor and non-tumor regions. Consequently, this augmentation further improves the network's segmentation efficacy for PD-L1 positive and negative regions. Furthermore, the PD-L1 expression regions demonstrate interconnection throughout the tissue section. Leveraging this topological prior knowledge, we integrate a connectivity modeling module (CM module) within the MTSL-based region attention module (MRA module) to enhance the precision of MTSL-based region attention localization. This integration further improves the structural similarity between the segmentation results and the ground truth. Extensive visual and quantitative results demonstrate that our supervised-learning-guided MRA module produces more interpretable attention and the introduced CM module provides accurate positional attention to the MRA module. Compared to other state-of-the-art networks, MCRANet exhibits superior segmentation performance with a dice similarity coefficient (DSC) of 79.6 % on the lung squamous cell carcinoma (LUSC) PD-L1 status dataset.

The Prognostic Role of Pre-Treatment Neutrophil-to-Lymphocyte Ratio in an Asian Cohort of Patients with Oropharyngeal Squamous Cell Carcinoma

Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC.

Impact of time from diagnosis to endoscopic submucosal dissection on curability in superficial esophageal squamous cell carcinoma.

To investigate the time delay effect from initial diagnosis to endoscopic submucosal dissection on superficial esophageal squamous cell carcinoma curability, considering the preoperative invasion depth. This study included superficial esophageal squamous cell carcinoma diagnosed as T1a-epithelial/lamina propria mucosa cancer (cEP/LPM; cancer invading up to the lamina propria mucosa) or cT1a-muscularis mucosa (MM)/T1b-submucosal cancer (cMM/SM1; cancer invading up to 200 µm into the submucosa) and treated using endoscopic submucosal dissection from January 2017 to December 2021. We compared curability in lesions treated within three months (early treatment group) versus those treated ≥7 months post-diagnosis (delayed treatment group). Curative resection criteria included lesions confined within the muscularis mucosae, with negative vertical margins, and with absence of lymphovascular invasion. Non-curative resection included all other cases. Among the 231 and 75 lesions in the early and delayed treatment groups, respectively, no significant difference was observed in non-curative resections for all lesions and cEP/LPM lesions (early: 194, delayed: 70). Conversely, the proportions were significantly higher in the delayed treatment group than in the early treatment group for cMM/SM1 lesions (early: 37, delayed: 5; p = 0.018). This study suggests that delayed endoscopic submucosal dissection does not significantly affect cEP/LPM lesions curability but is associated with reduced cMM/SM1 lesions curability. Prompt treatment is important for cMM/SM1, whereas delayed treatment may be acceptable for cEP/LPM.

DISP-04. SEX DIFFERENCES IN LUNG CANCER BRAIN METASTASES ADVERSE EVENTS

Abstract While sexual dimorphism is evident among adverse events (AEs) in response to treatments for many cancers, including brain tumors, little is known about sexual dimorphism among AE in brain metastases (BrM). As over 50% of BrM cases arise from lung cancer (LC), we examined sex differences in AEs associated with LC-BrM among individuals in the SEER-Medicare dataset aged ≥66 years at the time of LC diagnosis. Multivariable logistic regression models adjusted for demographic variables and Elixhauser comorbidity scores were used to analyze sex differences in AEs among individuals with BrM derived from primary LC. Analyses were stratified by the following histological subtypes: small-cell, adenocarcinoma, squamous cell carcinoma, or other non-small cell carcinomas. Additional variables analyzed included BrM treatment, age at BrM diagnosis, and year of diagnosis (at or before 2013/after 2013) to account for the introduction of targeted therapies. Differences in AE profiles, based by sex, in individuals diagnosed with LC-BrM were observed. Females diagnosed after 2013 with either small-cell, squamous cell, or other non-small cell carcinoma BrMs were more likely to experience headaches compared to males. Males diagnosed after 2013 with adenocarcinoma were more likely to experience brain herniation compared to females. Additionally, females aged 76 and older with small-cell BrM demonstrated an elevated risk of developing vision difficulties relative to males, whereas no significant sex difference observed in those under 76 years. Risk of most AEs decreased across all histological subtypes with receiving treatment after BrM diagnosis when compared to no treatment. This study underscores the existence of sex-specific differences in AEs among individuals aged 66 years and older diagnosed with LC-BrM. The AEs observed varied across histological subtypes, age cohorts, year of diagnosis, and treatment. Notably, receipt of treatment demonstrates consistent reduction in AE risk across all histological subgroups, underscoring the therapeutic benefit of treatment.

PRMT5/WDR77 Enhances the Proliferation of Squamous Cell Carcinoma via the ΔNp63α-p21 Axis

Protein arginine methyltransferase 5 (PRMT5) is a critical oncogenic factor in various cancers, and its inhibition has shown promise in suppressing tumor growth. However, the role of PRMT5 in squamous cell carcinoma (SCC) remains largely unexplored. In this study, we analyzed SCC patient data from The Cancer Genome Atlas (TCGA) and the Cancer Dependency Map (DepMap) to investigate the relationship between PRMT5 and SCC proliferation. We employed competition-based cell proliferation assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, flow cytometry, and in vivo mouse modeling to examine the regulatory roles of PRMT5 and its binding partner WDR77 (WD repeat domain 77). We identified downstream targets, including the p63 isoform ΔNp63α and the cyclin-dependent kinase inhibitor p21, through single-cell RNA-seq, RT-qPCR, and Western blot analyses. Our findings demonstrate that upregulation of PRMT5 and WDR77 correlates with the poor survival of head and neck squamous cell carcinoma (HNSCC) patients. PRMT5/WDR77 regulates the HNSCC-specific transcriptome and facilitates SCC proliferation by promoting cell cycle progression. The PRMT5 and WDR77 stabilize the ΔNp63α Protein, which in turn, inhibits p21. Moreover, depletion of PRMT5 and WDR77 repress SCC in vivo. This study reveals for the first time that PRMT5 and WDR77 synergize to promote SCC proliferation via the ΔNp63α-p21 axis, highlighting a novel therapeutic target for SCC.

INNV-22. CEREBELLOPONTINE EPIDERMOID CYST TO SQUAMOUS CELL CARCINOMA: MALIGNANT TRANSFORMATION, LEPTOMENINGEAL CARCINOMATOSIS, AND MANAGEMENT

Abstract BACKGROUND Intracranial epidermoid cysts (EDC) are rare, slow-growing, congenital tumors, that generally follow a benign course. EDCs have a rare potential for transformation to squamous cell carcinoma (SCC). We present a case of a malignant EDC transformation to SCC with leptomeningeal (LM) dissemination. METHODS Case report and review of literature. CASE PRESENTATION A 44-year-old female presented for evaluation of left-sided tinnitus and sensorineural hearing loss, which revealed a left cerebellopontine angle (CPA) tumor. She underwent a subtotal resection at age 47. One year later, she had rapid symptomatic recurrence of the cyst, as well as LM deposits of the right internal acoustic canal bundle, the left trigeminal nerve, and along the lumbar and sacral spine. She underwent repeat resection of the CPA lesion, with pathology now consistent with SCC, with CDKN2A loss. She received focal radiation therapy at the posterior fossa and the lumbar spine. SCC-directed chemotherapy with pembrolizumab and carboplatin followed by 5 cycles of pembrolizumab monotherapy was given as adjuvant therapy, prior to her developing symptomatic LM disease. CONCLUSION Malignant transformation of intracranial EDC is a rare occurrence in these typically benign tumours. Prognosis is especially poor when there is associated LM involvement, with median survival noted to be 10 months. Awareness of this phenomenon amongst clinicians is needed to ensure appropriate surveillance and aggressive treatment if it remains within patient wishes, though there is no consensus on recommendations for treatment. The patient presented has maintained disease stability with LM dissemination for over 10 months and ongoing, with a regimen of chemoradiotherapy informed by therapeutic approach to systemic SCC. To our knowledge, this is the first reported case of EDC to SCC transformation and LM dissemination stabilized with chemoradiotherapy using an immune-checkpoint inhibitor.

Rare carcinoma of the ampulla of Vater with mixed histologies: A case report

The current case is about a 62-year-old female presented with persistent fever for 10 days and yellowing of the skin for 5 days at our outpatient clinic. Laboratory tests revealed elevated levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Abdominal computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography revealed a mass in the ampulla of Vater, as well as dilatation of the intra- and extra-hepatic bile and pancreatic ducts. The patient underwent pancreaticoduodenectomy under general anesthesia. Post-operative pathological and immunohistochemical results confirmed a tumor located in the ampulla, measuring 1.5 × 1 × 1 cm. The main component of the tumor was a moderately differentiated pancreaticobiliary adenocarcinoma (ADC), combined with squamous cell carcinoma (SCC) as well as small cell neuroendocrine carcinoma (SCNEC). The cancer tissue infiltrated the entire intestinal wall, with no invasion of microvessels, lymphatic vessels, or nerves observed. Until 46 months later, there was no tumor recurrence or distant metastasis. We present an uncommon case of ADC of the ampulla of Vater combined with SCC and SCNEC. Carcinoma of the ampulla of Vater may have mixed histological components; therefore, in cases of ampullary carcinoma, appropriate specimen collection is necessary, and further studies with more focus on histological origins are required.

The Expression of HPV-16 E5 Oncoprotein Impacts the Transcript Profiles of FGFR2 and EMT-Related Genes in Preneoplastic Anal Epithelium Lesions

Anal Squamous Cell Carcinoma (SCCA) is a rare Human Papillomavirus type 16 (HPV16)-associated carcinoma whose pathogenesis is still poorly understood. Recent studies based on biopsy and Next Generation Sequencing (NGS) approaches have linked the viral episomal status to aggressive SCCA phenotypes, suggesting a potential role of the 16E5 oncoprotein in tumor development. Our previous findings indicated that 16E5 induces Fibroblast Growth Factor Receptor 2 (FGFR2) isoform switching, aberrant mesenchymal FGFR2c expression, Epithelial Mesenchymal Transition (EMT), and cell invasion in various in vitro human keratinocyte models, as well as in the in vivo context of cervical Low-grade Squamous Intraepithelial Lesions (LSILs). To further explore the role of 16E5 in epithelial carcinogenesis, this study aims to investigate the molecular profile in HPV-related anal lesions. The results showed a significant positive correlation between 16E5 and FGFR2c, as well as 16E5 or FGFR2c and key EMT-related transcription factors, particularly in the group of HPV16 positive anal samples not containing without high grade lesions. Additionally, by coupling the molecular analysis with an interactome investigation, we hypothesized a potential functional interplay between the Ca2+ channel Transient Receptor Potential Ankyrin 1 (TRPA1) and FGFR2c, mediated by 16E5 during the establishment of the oncogenic signaling. These findings will help to elucidate the actual relevance of 16E5 in the early progression of anal lesions and contribute to determine its potential as target for future preventive approaches for HPV16-positive SCCA.

Clinicopathologic Features of Oral Verrucous Carcinoma: A Systematic Review and Meta-Analysis.

To further characterize the clinicopathologic features of oral verrucous carcinoma. In accordance with PRISMA guidelines, a systematic review of the Medline, Web of Science, Embase, and Cochrane databases was performed in search of articles evaluating clinicopathologic features of oral verrucous carcinoma. Primary outcomes of interest included tumor subsites, T-staging, rates of cervical lymph node metastases, rates of distant metastases, 5-year survival (overall, disease-free, or disease-specific), and recurrence rates. Meta-analysis was performed using a random effects model. Nineteen articles with a total of 1458 subjects were ultimately included in the analysis. There were 17 studies with a total of 1353 patients reporting verrucous carcinoma subsites and the buccal mucosa (59.2%, 55.1%-63.3%) (I2 = 98.1%) had the highest incidence of involvement. There were 10 papers with 277 patients reporting on rates of cervical lymph node metastases from surgical pathology yielding a pooled rate of 0% (0%-2.3%) (I2 = 1%). There were 14 studies with a collective 712 patients commenting on rates of distant metastases and collectively, none were reported, yielding a pooled rate of 0% (0%-0%) (I2 = 0%). Five year survival data was generally favorable relative to oral squamous cell carcinoma but was insufficient for meta-analysis. An international collection of evidence supports that pure oral verrucous carcinoma is a relatively indolent, non-metastasizing malignancy associated with areca nut consumption. A reliance on traditional squamous cell carcinoma staging and treatment algorithms for verrucous carcinoma patients can predispose to overtreatment.

Comparative analysis of the expression of р16, PD-L1 in squamous cell carcinoma of the oropharynx and CUP syndrome

Introduction. metastases in the absence of a primary tumor (cancer of unknown primary (Cup) syndrome) are diagnosed in 2–4 % of malignant tumor cases. This pathology is characterized by early metastatic dissemination, weak response to conventional chemotherapy, and aggressive progression. The use of checkpoint inhibitors targeting programmed cell death protein 1 (pD-1) and its ligand (pD-L1) has shown good results in treatment of various cancers including oropharyngeal squamous cell carcinoma (OpSCC). In Cup syndrome, the effectiveness of checkpoint inhibitors is rarely investigated, and pD-L1 expression is often not measured.Aim. To compare the frequency of p16 and pD-L1 hyperexpression in OpSCC and Cup syndrome, and to analyze dependency of survival rates on the level of expression of p16, the most important prognostic marker.Materials and methods. The study included 121 patients (59 with OpSCC and 62 with Cup syndrome) who received medical treatment in the multidisciplinary medical Center “medical City” (Tyumen) and Chelyabinsk Oncological Center of Oncology and Nuclear medicine between 2019 and 2023. Immunohistochemical examination was performed using the vENTANA Benchmark gX with primary antibodies against pD-L1 (clone Sp263, uSA) and р16 (uS Biological, uSA). Statistical analysis of the data was performed using SpSS 26 software. Long-term treatment outcomes were evaluated using 1-, 3-, 5-year survival rates and median survival. Overall survival was analyzed using the kaplan-meier method. Statistical significance of the differences was evaluated using the Cox model.Results. The studied groups did not differ by sex (p = 0.472), age (р = 0.640), and N stage (р = 0.262). patient age in the whole population varied between 42 and 81 years (median age 61.89 ± 11.9 years; mean age 60.81 ± 9.8 years). pD-L1 expression rate was higher in Cup syndrome at 92 % compared to 73 % in OpSCC (statistically significant difference; р = 0.01). Analysis of the association of ORSCC and Cup syndrome with human papilloma virus showed statistically significant difference in p16 hyperexpression: patients with OpSCC had p16-positive status more frequently (53 % of cases) while patients with Cup syndrome mostly had p16-negative status (73 % of cases). mean life expectancy of patients with OpSCC and p16-positive status was 62.65 months (95 % confidence interval 54.98–70.31), minimal observation period was 12 months, maximal was 70 months. mean life expectancy of patients with Cup syndrome and positive p16 status was 66.22 months (95 % confidence interval 56.35–76.10), minimal observation period was 12 months, maximal was 70 months. No statistically significant differences in survival rates of patients with OpSCC and Cup syndrome were found (р = 0.999).Conclusion. The study showed higher pD-L1 expression in patients with Cup syndrome compared to patients with OpSCC: 92 and 73 %, respectively (р = 0.01). The obtained results highlight the importance of routine pD-L1 expression evaluation in patients with Cup syndrome. The frequency of p16 hyperexpression was higher in OpSCC compared to Cup syndrome: 53 % versus 27 % (р = 0.02) which agrees with the worldwide epidemiological data: among all malignant neoplasms of the head and neck, Hpv infection is most common in OpSCC. Therefore, it serves as an important sign of hidden oropharyngeal cancer in Cup syndrome.

Medium-term oncological outcome endoscopic surgery malignant tumors of the nasal cavity and paranasal sinuses

Introduction. Transnasal endoscopic resection of sinonasal tumors is currently used in many clinics around the world. Short- and long-term oncological outcomes primarily depend on tumor histology. However, most currently existing studies are based on a small number of observations due to the rarity and heterogeneity of sinonasal malignancy.Aim. To evaluate short- and medium-term oncological outcomes of treatment of malignant sinonasal tumors. Materials and methods. The study is based on retrospective analysis of 95 patients who underwent endoscopic surgery for sinonasal malignancy between 2014 and 2023 at the N.N. Blokhin National medical Research Center of Oncology. Squamous cell carcinoma was diagnosed in 27 (28.4 %) patients, olfactory neuroblastoma in 13 (13.7 %), mucosal melanoma in 30 (31.6 %), adenocarcinoma in (6.3 %), adenoid cystic carcinoma in 7 (7.3 %), sarcomas in 12 (12.7 %). Results. In the study group, 2-years overall survival and recurrence-free survival were 81.3 and 61.4 % respectively, survival without local recurrence was 87.5 %. The outcomes significantly depended on tumor histology.Conclusion. Oncological outcomes of endoscopic resections of sinonasal tumors significantly depend on tumor histology, but in general they allow to achieve good local control. Small number of observations, variety of histological forms, and short follow-up periods do not allow to accurately evaluate the effectiveness of this approach for each tumor type. further research in large populations is needed to establish risk factors.

Head and Neck Squamous Cell Carcinoma: Insights from Dual-Energy Computed Tomography (DECT)

Head and neck cancer represents the seventh most common neoplasm worldwide, with squamous cell carcinoma being the most represented histologic variant. The rising incidence of the neoplastic pathology of this district, coupled with the drastic changes in its epidemiology over the past decades, have posed significant challenges to physicians worldwide in terms of diagnosis, prognosis, and treatment. In order to meet these challenges, a considerable amount of effort has been spent by the authors of the recent literature to explore new technologies and their possible employment for the better diagnostic and prognostic definition of head and neck squamous cell carcinoma (HNSCC). Among these technologies, a growing interest has been gathering around the possible applications of dual-energy computed tomography (DECT) in head and neck pathology. Dual-energy computed tomography (DECT) utilizes two distinct X-ray energy spectra to obtain two datasets in a single scan, allowing for material differentiation based on unique attenuation profiles. DECT offers key benefits such as enhanced contrast resolution, reduced beam-hardening artifacts, and precise iodine quantification through monochromatic reconstructions. It also creates material decomposition images, like iodine maps, aiding in tumor characterization and therapy assessment. This paper aims to summarize recent findings on the use of DECT in HNSCC, providing a comprehensive overview to aid further research and exploration in the field.

Utility of patient-derived xenografts to evaluate drug sensitivity and select optimal treatments for individual non-small-cell lung cancer patients.

Patient-derived xenograft (PDX) is currently considered a preferred preclinical model to evaluate drug sensitivity, explore drug resistance mechanisms, and select individualized treatment regimens. Histopathological examination, immunohistochemistry and whole-exome sequencing confirmed similarity between our PDX tumors and primary tumors in terms of morphology and genetic characteristics. The drug reactivity of the PDX tumor was validated in vivo. The mechanisms of acquired resistance to Osimertinib PDX tumors were investigated by WES and WB. We successfully established 13 NSCLC-PDXs derived from 62 patients, including eight adenocarcinomas, four squamous-cell carcinoma, and one large-cell neuroendocrine carcinoma. Histological subtype and clinical stage were significant factors affecting the successful PDXs establishment. The treatment responses to conventional chemotherapy in PDXs were entirely consistent with that of their corresponding patients. According to the genetic status of tumors, more appropriate targeted agents were selected in PDXs for their corresponding patients as alternative treatment options. In addition, a PDX model with acquired resistance to osimertinib was induced, and the overactivation of RAS mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) signaling pathway caused by the dual-specificity phosphatase 6 (DUSP6) M62I mutation was found to play a key role in the development of osimertinib resistance. Trametinib, a specific inhibitor of the MAPK-ERK pathway significantly slowed down the tumor growth in osimertinib-resistant PDX models, providing an alternative treatment in patients after osimertinib failure.

Oral mucosa reconstruction methods in cancer patients

Resection of malignant neoplasms of the oral cavity causes esthetic, functional, and anatomical defects irrespective of the advancement of tumor process. The methods of oral cavity organ reconstruction include the use of distant flaps and microsurgical autotransplantation. microsurgical techniques have limits and are not always applicable in clinical practice.The article presents the main techniques of oral cavity organ reconstruction alternative to microsurgical techniques. Detailed literature review on this topic is performed, advantages and disadvantages of the various methods of defect reconstruction are presented. In clinical practice, the use of distant flaps is an adequate alternative to microsurgical autotransplantation. This method can be successfully used in weakened patients with locally advanced squamous cell carcinoma of the oral mucosa.

A population-based study using nomograms to predict overall and cancer-specific survival in HPV-associated CSCC.

Constructing and validating two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) in cutaneous squamous cell carcinoma (CSCC) correlated with human papillomavirus (HPV) infection was the main goal of this study. We constructed predictive models for OS and CSS incidence in HPV infection-associated CSCC using information from 2238 patients in the Surveillance, Epidemiology, and End Results (SEER) database and screened the variables by LASSO regression, Cox univariate regression, and Cox multifactorial regression models, which were calibrated and validated by internal and external cohorts. Finally, all patients were categorized into intermediate-risk, low-risk, and high-risk groups based on the optimal threshold calculated from the total score. Multivariate analysis showed that HPV infection status, marital status, tumor metastatic stage, surgical status, radiotherapy status, lymph node biopsy, local lymph node dissection, primary tumor status, and bone metastasis were risk factors for OS and CSS. The C index, the time-dependent area under the receiver-operating characteristic curve, and the column-line diagrams of the calibration plot were among the excellent-performance metrics that were effectively displayed. Moreover, the decision curve analysis of the two nomograms consistently revealed their favorable net benefits spanning 1, 2, and 3 years. In addition, the survival curves indicate that each of the two risk classification systems clearly differentiates high, medium, and low risk groups. These meticulously crafted nomograms stand poised to serve as indispensable instruments in clinical practice, empowering clinicians to adeptly communicate with patients regarding their prognostic outlook over the forthcoming 1, 2, and 3 years.

Expression of the lncRNA TPT1-AS1 in lung squamous cell carcinoma and its prognostic value.

Lung squamous cell carcinoma is typically associated with a poor prognosis, highlighting the need for a reliable prognostic marker. Given that the long noncoding RNA TPT1-AS1 has demonstrated aberrant expression in numerous cancers, the prognostic significance of TPT1-AS1 in LUSC was examined. The present study included 115 patients diagnosed with LUSC. The expression levels of TPT1-AS1 and miR-4726-5p in tissues and cells were assessed using RT-qPCR, while the correlation between TPT1-AS1 expression and clinicopathological features was analyzed through the chi-square test. Binding sites between TPT1-AS1 and miR-4726-5p were predicted using a database and confirmed via a dual-luciferase reporter assay. The Pearson correlation coefficients were calculated to determine the relationship between TPT1-AS1 and miR-4726-5p in tumor tissues. The impacts of TPT1-AS1 and miR-4726-5p on cells were evaluated through CCK-8 and Transwell assays. TPT1-AS1 expression was found to be reduced, while miR-4726-5p expression was upregulated in LUSC tissues. Patients exhibiting low TPT1-AS1 expression experienced shorter overall survival. Moreover, TPT1-AS1 was identified as an independent prognostic factor. A dual luciferase reporter assay validated that TPT1-AS1-WT targeted and bound to miR-4726-5p. Additionally, an inverse correlation was observed between miR-4726-5p and TPT1-AS1 in tumors. Cell experiments indicated that the overexpression of TPT1-AS1 led to a decrease in miR-4726-5p expression, consequently inhibiting cell proliferation, migration, and invasion. TPT1-AS1 targets miR-4726-5p, and overexpression of TPT1-AS1 has the potential to serve as a prognostic marker for LUSC and can significantly influence LUSC progression.

Challenges and Considerations in Diagnosing and Managing p16+-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC) with Neck Metastasis: Implications of p16 Positivity, Tobacco Exposure, and De-Escalation Strategies

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. Methods: A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. Results: HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. Conclusions: A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

Demographic Characteristics of Locally Advanced Laryngeal Cancer with Concurrent Chemo Radiotherapy along with Weekly Paclitaxel versus Weekly Cisplatin in Rajshahi Medical College

Modern multi-modality approaches using definitive concurrent chemoradiation has shown promising results in the treatment of locally advanced laryngeal cancer with intact cartilage and functional larynx. The aim of this study to estimate demographic Characteristics of Locally Advanced Laryngeal Cancer with Concurrent Chemo Radiotherapy along with Weekly Paclitaxel versus Weekly Cisplatin. This quasi-experimental study was conducted at the Department of Radiotherapy, Rajshahi Medical College Hospital, from January 2021 – June 2022 following ethical approval. Total 60 patients with locally advanced squamous cell carcinoma of larynx were included and divided into Arm-A (n=30) and Arm-B (n=30). After taking informed written consent, patients were given injection paclitaxel 30mg/m2 (Arm-A) or injection cisplatin 40mg/m2 (Arm-B) along with radiotherapy 66Gy in 33 fractions over 6.5 weeks. In this study, mean age of all study patients was 56.03±8.88 (SD) years with male predominance (88.3%). Demographic characteristics were similar across the two arms regarding age, gender, and tobacco history (p>0.05). Treatment response was evaluated at 6, 12 and 24 weeks after the completion of treatment. In Arm- A 80.00% showed complete response whereas in Arm- B showed 70.00%. Partial response was 20.00% and 30.00% in Arm-A and Arm-B respectively. Both Arm-A and Arm-B had similar rate of treatment response at each follow up (p>0.05).

Gastroesophageal reflux disease and risk of incident lung cancer: A large prospective cohort study in UK Biobank.

Some pathogenic mechanisms suggest a potential relationship between gastroesophageal reflux disease (GERD) and respiratory diseases. However, evidence regarding the association between GERD and lung cancer is mixed. We aim to explore this relationship based on data from the large-scale UK Biobank study. We performed a cross-sectional and prospective cohort study in 501,569 (45.58% male) individuals included in the UK Biobank at baseline (2006-2010). The Cox proportional hazards model and logistic regression models were used to assess the relationship between GERD and lung cancer, small cell lung cancer (SCLC), lung squamous cell carcinoma (LUSC), and lung adenocarcinoma (LUAD). During a mean follow-up of 11.54 years, 3,863 (0.84%) incident lung cancer cases were identified. In the cross-sectional analysis using logistic models, significant associations were found between GERD and prevalent lung cancer cases (odds ratio [OR] = 1.87, 95% confidence interval [95% CI]: 1.45-2.38) and subtypes of lung cancer, with an OR (95% CI) of 3.19 (1.47-6.79) for SCLC, 2.08 (1.33-3.21) for LUSC, 1.85 (1.15-2.91) for LUAD. In the follow-up analysis using Cox models, GERD was associated with an increased risk of lung cancer (hazard ratio [HR] = 1.24, 95%CI: 1.14-1.34). Similar associations were also observed between GERD and SCLC (HR = 1.39, 95% CI: 1.09-1.78), LUSC (HR = 1.40, 95% CI: 1.18-1.65), and LUAD (HR = 1.17, 95% CI: 1.02-1.33). The risk of lung cancer resulting from GERD was mainly elevated in former smokers (HR = 1.38, 95% CI: 1.23-1.54) and current smokers (HR = 1.18, 95% CI: 1.04-1.34), but not in never-smokers (HR = 0.89, 95% CI: 0.70-1.14). No significant association was observed in former smokers who had quit smoking for at least 25 years. We found that GERD was positively associated with an increased risk of lung cancer, especially among smokers. Awareness of this association may be beneficial for prevention and treatment strategies of both diseases.

MMP12 disrupts epithelial barrier integrity in oral lichen planus by degrading fibronectin.

Oral lichen planus (OLP) is a chronic inflammatory disorder featured with T lymphocytes infiltration and epithelial basement membrane breakdown. Although matrix metalloproteinase-12 (MMP12) is reported to be involved in the pathogenesis of oral diseases such as oral squamous cell carcinoma and periodontitis, the roles of MMP12 in the context of OLP remain poorly understood. Here, we demonstrate that MMP12 in macrophages derived from mucosal diseased tissues compromises the epithelial barrier integrity in OLP. The increased MMP12 facilitates fibronectin degradation in keratinocytes, leading to oral epithelial barrier disruption. Overexpression of fibronectin in oral keratinocytes prevents epithelial barrier from MMP12-induced damage. In addition, pharmacological inhibition of MMP12 reverses keratinocyte barrier disruption in a cell model. Altogether, our study reveals that MMP12 mediates oral epithelial barrier integrity in the setting of OLP.