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International Journal of Oral Science Sep 2023Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance,... (Review)
Review
Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
Topics: Humans; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37736748
DOI: 10.1038/s41368-023-00249-w -
Medical Sciences (Basel, Switzerland) Jun 2023Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands,... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11-12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations.
Topics: Male; Female; Humans; Adolescent; Child; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomavirus Infections; Risk Factors
PubMed: 37367741
DOI: 10.3390/medsci11020042 -
Signal Transduction and Targeted Therapy Aug 2023
Topics: Humans; Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy; Esophageal Neoplasms; Transcriptome; Carcinoma, Squamous Cell
PubMed: 37563120
DOI: 10.1038/s41392-023-01518-0 -
EBioMedicine Nov 2023Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of...
BACKGROUND
Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive.
METHODS
Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas.
FINDINGS
We found CD8 T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1 macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell-cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs.
INTERPRETATION
Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment.
FUNDINGS
National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).
Topics: Female; Humans; Carcinoma, Squamous Cell; Uterine Cervical Neoplasms; CD8-Positive T-Lymphocytes; Sequence Analysis, RNA; Adenocarcinoma; Tumor Microenvironment
PubMed: 37879219
DOI: 10.1016/j.ebiom.2023.104846 -
Nature Communications Aug 2023The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial...
The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies.
Topics: Humans; Carcinoma, Squamous Cell; Transcriptome; Mouth Neoplasms; Gene Expression Profiling; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37596273
DOI: 10.1038/s41467-023-40271-4 -
Current Oncology (Toronto, Ont.) Jul 2023Non-melanoma skin cancer of the head and neck (NMSCHN) is one of the most common malignancies worldwide, and its incidence is growing at a significant rate. It has been... (Review)
Review
Non-melanoma skin cancer of the head and neck (NMSCHN) is one of the most common malignancies worldwide, and its incidence is growing at a significant rate. It has been found to be aggressive in its spread and has the capacity to metastasize to regional lymph nodes. Cutaneous squamous cell carcinoma (cSCC) has a considerably high mortality rate. It has remarkable characteristics: diameter >2 cm, depth >5 mm, high recurrence, perineural invasion, and locoregional metastases. Aggressive cSCC lesions most commonly metastasize to the parotid gland. Also, immunocompromised patients have a higher risk of developing this aggressive cancer along with the worst prognostic outcomes. It is very important to discuss and assess the risk factors, prognostic factors, and outcomes of patients with cSCC, which will give clinicians future directives for making modifications to their treatment plans. The successful treatment of aggressive cSCC of the head and neck includes early detection and diagnosis, surgery alone or adjuvant chemotherapy, and radiotherapy as required. Multimodal therapy options should be considered by clinicians for better outcomes of aggressive cSCC of the head and neck.
Topics: Humans; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Skin Neoplasms; Head and Neck Neoplasms; Neoplasm Staging
PubMed: 37504347
DOI: 10.3390/curroncol30070487 -
Laryngo- Rhino- Otologie May 2024The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common... (Review)
Review
The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up.
Topics: Skin Neoplasms; Humans; Interdisciplinary Communication; Carcinoma, Squamous Cell; Carcinoma, Basal Cell; Patient Care Team; Carcinoma, Merkel Cell; Intersectoral Collaboration; Neoplasm Staging
PubMed: 38697144
DOI: 10.1055/a-2171-4570 -
Advanced Science (Weinheim,... Jul 2023Cell-cell interactions are the fundamental behaviors to regulate cellular activities. A comprehensive evaluation of intercellular interactions requires direct profiling...
Cell-cell interactions are the fundamental behaviors to regulate cellular activities. A comprehensive evaluation of intercellular interactions requires direct profiling of various signaling behaviors simultaneously at the single-cell level, which remains lacking. Herein, an integrative single-cell secretion analysis platform is presented to profile different secreted factors (four proteins, three extracellular vesicles (EV) phenotypes), spatial distances, and migration information (distances and direction) simultaneously from high-throughput paired single cells using an antibody-barcode microchip. Applying the platform to analyze the tumor-stromal and tumor-immune interactions with the human oral squamous cell carcinoma (OSCC) cell lines and primary OSCC cells reveals that the initial distances between cells would determine their migratory distances and direction to approach stable organization. The cell-cell in close proximity enhances protein secretions while attenuating EV secretions. Migration has a more profound correlation with protein secretions than EV secretions, in which absolute migration distance affects protein secretions significantly but not the direction. These findings highlight the significance of spatial organization in regulating cell signaling behaviors and demonstrate that the integrative single-cell secretion profiling platform is well-suited for a comprehensive dissection of intercellular communication and interactions, providing new avenues for understanding cell-cell interaction biology and how different signaling behaviors coordinate within the tumor microenvironment.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Cell Communication; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 37186381
DOI: 10.1002/advs.202301018 -
Oral erythroplakia and oral erythroplakia-like oral squamous cell carcinoma - what's the difference?BMC Oral Health Nov 2023Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In...
BACKGROUND
Oral erythroplakia (OE) is a rare oral potentially malignant disorder, that has a high rate of malignant transformation. The definition of OE still lacks uniformity. In particular, lesions that look clinically like erythroplakias, but are histopathologically diagnosed as squamous cell carcinomas are still sometimes called erythroplakias. The purpose of this study is to present demographic and clinicopathologic features of a series of OEs and clinically oral erythroplakia -like squamous cell carcinomas (OELSCC), to study their differences and to discuss the definition of OE.
METHODS
A multicenter retrospective case series of OEs and OELSCCs. Descriptive statistics were used to analyze the data.
RESULTS
11 cases of OEs and 9 cases of OELSCCs were identified. The mean age of the OE patients was 71 years and 72.7% were female, while the mean age of the OELSCC patients was 69 years, and all were female. 9% of the OE and 22% of the OELSCC patients had smoked or were current smokers. 72.7% of the OEs and 55.5% of OELSCCs were uniformly red lesions. 63.6% of the OE and 22% of the OELSCC patients had a previous diagnosis of oral lichenoid disease (OLD). The malignant transformation rate of OE was 9% in a mean of 73 months.
CONCLUSIONS
OE and OELSCC may arise de novo or in association with OLD. Tobacco and alcohol use were not prevalent in the present cases. The clinical features of OEs and OELSCC are similar, but symptoms, uneven surface and ulceration may be more common in OELSCCs than in OEs. Clinical recognition of OE is important since it may mimic other, more innocuous red lesions of the oral mucosa. The diagnosis of OE requires biopsy and preferably an excision. Clarification of the definition of OE would aid in clinical diagnostics.
Topics: Humans; Female; Aged; Male; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Retrospective Studies; Mouth Diseases; Erythroplasia; Mouth Mucosa; Oral Ulcer; Head and Neck Neoplasms; Leukoplakia, Oral; Precancerous Conditions
PubMed: 37957684
DOI: 10.1186/s12903-023-03619-2 -
Autoimmunity Dec 2023This study focussed on exploring the prognostic prediction performance of the growth arrest and DNA damage-inducible 45 beta (GADD45B) and its associations with T-cell...
BACKGROUND
This study focussed on exploring the prognostic prediction performance of the growth arrest and DNA damage-inducible 45 beta (GADD45B) and its associations with T-cell activity and immune soakage in different malignancies, especially lung squamous cell carcinoma (LUSC).
METHODS
We applied TIMER database for comparing the expressions of GADD45B among different cancers. OncoLnc, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Kaplan-Meier utilised to evaluate the prognostic prediction performance of GADD45B. Besides, the associations of GADD45B with clinical stage, associated gene markers, and immune examined through TISIDB, GEPIA2, and Tumour Immune Estimation Resource (TIMER). Biological processes (BPs) and KEGG enrichment analyses were performed to illustrate the possible role of GADD45B in LUSC. The miRWalk database was adopted to analyse the gene miRNA interaction network of GADD45B in LUSC.
RESULTS
GADD45B expression was decreased in most of the malignancies, with relation to the poor prognosis in LUSC. GADD45B also significantly affected the survival of LUSC subgroups divided by clinic data. GADD45B significantly correlates with and may stimulate T cell exhaustion in LUSC.
CONCLUSIONS
GADD45B is a prognostic indicator in multiple tumours, especially in LUSC. Moreover, modulating GADD45B expression may improve immunotherapy efficacy in LUSC.
Topics: Humans; T-Cell Exhaustion; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Lung Neoplasms; Lung; Prognosis; Gene Expression Regulation, Neoplastic; Antigens, Differentiation
PubMed: 37165780
DOI: 10.1080/08916934.2023.2209706