New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

Nanomaterials for refining tumor microenvironment and enhancing therapy in head and neck squamous cell carcinoma: a review

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and lethal solid tumor with a high mortality rate. Conventional cancertreatments, including surgery, radiotherapy, and chemotherapy, primarily target cancer cell eradication. However, uncontrolled proliferation and metabolic activities of these cells result in abnormalities in nutrient levels, hypoxia, and immunosuppression within the tumor microenvironment (TME). These factors constrain the efficacy of traditional treatments by promoting drug resistance, recurrence, and metastasis. Nanomaterials (NMs), such as nanozymes, can exhibit enzymatic activity similar to that of natural enzymes and offer a promising avenuefor the direct modification of the TME through catalytic oxidation-reduction processes. Moreover, they can serve as sensitizers or drug deliverycarriers, enhancing the efficacy of traditional treatment methods. Recently, NMs have garnered significant attention from oncologists. Thisreview begins with an overview of the composition and unique characteristics of the TME. Subsequently, we comprehensively exploredthe application of NMs in the treatment of HNSCC. Finally, we discuss the potential prospects and challenges associated with usingNMs in biomedical research.

A pilot study of the relative number of circulating tumor cells and leukocytes containing actin-binding proteins in head and neck cancer patients

Circulating tumor cells(CTCs)play an important role in tumor metastases,which is positively correlated with an increased risk of death.Actin-binding proteins,including cofilin(CFL1),profilin 1(PFN1),and adenylate cyclase-associated protein 1(CAP1),are thought to be involved in tumor cell motility and metastasis,specifically in head and neck squamous cell carcinoma(HNSCC).However,currently,there are no published studies on CFL1,PFN1,and CAP1 in CTCs and leukocytes in HNSCC patients.We assessed serum levels of CFL1,PFN1,and CAP1 and the number of CTCs and leukocytes containing these proteins in blood from 31 HNSCC patients(T1-4N0-2M0).The analysis used flow cytometry and an enzyme-linked immunosorbent assay kit.We found that CAP1+CTCs and CAP1+leukocyte subpopulations were prevalent in these HNSCC patient samples,while the prevalence rates of CFL1+and PFN1+CTCs were relatively low.Patients with stage T2-4N1-2M0 had CFL1+and PFN1+CTCs with an elevated PFN1 serum level,compared with the T1-3N0M0 group.In summary,the PFN1 serum level and the relative number of PFN1+CD326+CTCs could be valuable prognostic markers for HNSCC metastases.The current study is the first to obtain data regarding the contents of actin-binding proteins(ABPs)in CTCs,and leukocytes in blood from HNSCC patients.This is also the first to assess the relationship between the number of CTCs subgroups and disease characteristics.

Clinicopathological study of malignant peripheral nerve sheath tumors in the head and neck:Case reports and review of literature

BACKGROUND Malignant peripheral nerve sheath tumor(MPNST)is a rare and aggressive soft tissue sarcoma that poses a major diagnostic and therapeutic challenge.CASE SUMMARY We retrospectively reviewed patients with head and neck MPNSTs treated in our hospital from 2000 to 2021.The clinical features,pathological manifestations,treatments,and prognoses were summarized.We also reviewed the literature,focusing on MPNST in the mandible and maxilla.The study population consisted of five women and five men aged 22–75 years(mean age,49 years).Of the 10 patients,7 were initial cases and 3 were recurrent cases.All lesions were sporadic.The most common site was the mandible.The most frequently encountered symptoms were a progressive mass and local swelling.Complete or partial loss of trimethylation at lysine 27 of histone H3(H3K27me3)was evident on staining in four of nine cases(one case was excluded due to lack of tissue for evaluation of loss of H3K27me3).The 2-and 5-year disease-specific survival rates were 86%a nd 43%,respectively.The average survival time was 64 mo.CONCLUSION MPNST is a highly malignant tumor with a poor prognosis,prone to a high risk of recurrence and distant metastasis.Complete surgical resection is the main treatment.

Research Progress in Surgical Management of Head and Neck Tumors Involving the Carotid Artery

The surgeons adopt the comprehensive treatment method basing on surgery When head and neck tumors involve the carotid artery. At present, there are four surgical treatments, namely, dissection of carotid artery tumor, resection of carotid artery, revascularization after carotid resection, endoarterial implantation of covered stent combined with surgical resection. However, there is currently no consensus on the standard surgical approach to choose. This paper describes the four surgical methods, which are expected to be helpful for head and neck surgeons to choose the surgical methods for head and neck tumors involving the carotid artery.

Prototyping: Major Advance in Surgical Planning and Customizing Prostheses in Patients with Bone Tumors of the Head and Neck

Major resections of bone tumors of the head and neck, owing to their small dimensions and their proximity to the organs in this region, cause important functional and aesthetic problems that significantly compromise patients’ quality of life. Therefore, therapeutic planning should always extend beyond the resection to include functional and aesthetic reconstruction, preferably immediately. Microsurgical reconstruction represents a significant advance, but has not yet been perfected. Rapid prototyping (RP) comes as a new technology for the purpose of assisting the surgeon in the visual and tactile aspects of surgery, providing diagnostic accuracy and increasing the success of surgical planning. The authors demonstrate the technological advances in the manufacture of customized mandibular prostheses with the assistance of RP and practical applications of these methods.

Effect of Wearing a Maxillofacial Prosthesis on Masticatory Rhythm Improvement in Mandibulectomy Patients

Background: Recording jaw movement rhythms in patients with jaw defects is challenging using conventional tracking devices. However, masticatory rhythm is crucial for masticatory performance and nutritional intake. This study aimed to explore the impact of using a maxillofacial prosthesis to restore masticatory rhythm in mandibulectomy patients with a novel wearable device. Methods: Twelve patients who underwent mandibulectomy and were rehabilitated with maxillofacial prosthesis were recruited. Chewing rate, cycle durations, coefficient of variation of cycle durations (CV), changing times of skin morphology on the back of the ear pinna area (SM), and masticatory performance were measured during gum chewing without and with a denture using a wearable jaw movement rhythm tracking device. A paired t-test and the Pearson correlation coefficient were used for statistical analysis. Results: The chewing rate increased by 8.6 cycles/min with dentures (P P = 0.01). The CV and SM decreased with dentures (P = 0.004 and P = 0.01, respectively). Significant correlations were found between the CV and SM without dentures (P = 0.004). Conclusion: 1. Wearing maxillofacial prostheses can improve masticatory rhythm in patients who undergo mandibulectomy with Eichner B2 occlusal supports. 2. The wearable device is available for measuring masticatory rhythm in patients with jaw defects in clinics. 3. Changing times of the skin morphology on the back of the ear pinna indicate jaw movement stability through a simpler process than the coefficient of variation of cycle durations.

Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer

AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma(HNSCC). METHODS: In this retrospective study,19 HNSCC patients underwent pre- and intra-treatment DCEMRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images,generating maps of volume transfer rate(Ktrans) and volume fraction of the extravascular extracellular space(ve). Image texture analysis was then employed on maps of Ktrans and ve,generating two texture measures: Energy(E) and homogeneity.RESULTS: No significant changes were found for the mean and standard deviation for Ktrans and ve between pre- and intra-treatment(P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans,relative to pretreatment scans(P < 0.04). CONCLUSION: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.

Collision tumor of squamous cell carcinoma and neuroendocrine carcinoma in the head and neck:A case report

BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and squamous cell carcinoma(SCC)in the nasal cavity and paranasal sinus.She received operation,concurrent chemoradiotherapy,and then two cycles of palliative chemotherapy.Follow-up at 12 mo after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis.A literature review of previous 26 cases diagnosed with collision tumor of NEC and SCC in the head and neck was also undertaken.CONCLUSION It is challenging to manage collision tumors because there are two morphologically and etiologically distinct tumors.Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.

Histone modifications:Targeting head and neck cancer stem cells

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer worldwide, and is responsible for a quarter of a million deaths annually. The survival rate for HNSCC patients is poor, showing only minor improvement in the last three decades. Despite new surgical techniques and chemotherapy protocols, tumor resistance to chemotherapy remains a significant challenge for HNSCC patients. Numerous mechanisms underlie chemoresistance, including genetic and epigenetic alterations in cancer cells that may be acquired during treatment and activation of mitogenic signaling pathways, such as nuclear factor kappa-light-chain-enhancer-of activated B cell, that cause reduced apoptosis. In addition to dysfunctional molecular signaling, emerging evidence reveals involvement of cancer stem cells(CSCs) in tumor development and in tumor resistance to chemotherapy and radiotherapy. These observations have sparked interest in understanding the mechanisms involved in the control of CSC function and fate. Post-translational modifications of histones dynamically influence gene expression independent of alterations to the DNA sequence. Recent findings from our group have shown that pharmacological induction of posttranslational modifications of tumor histones dynamically modulates CSC plasticity. These findings suggest that a better understanding of the biology of CSCs in response to epigenetic switches and pharmacological inhibitors of histone function may directly translate to the development of a mechanism-based strategy to disrupt CSCs. In this review, we present and discuss current knowledge on epigenetic modifications of HNSCC and CSC response to DNA methylation and histone modifications. In addition, we discuss chromatin modifications and their role in tumor resistance to therapy.

ANALYSIS OF 26,826 PATIENTS WITH TUMORS IN THE HEAD AND NECK

A series of 26,826 patients with head and neck tumer as confirmed by pathology from January 1970 to December 1989 are analyzed. It accounted for 39. 5% of all the tumors blopsied in the same interval. In this series, 72. 4% was malignant which accounted for 45. 77% of malignant tumors in different parts of the whole body. For benign tumors in the head and neck, the ratio of male to female was 0. 84:1, and for malignant tumors In the head and neck it was 2. 4:1. The most frequently involved site by the malignant tumors were :nasopharynx, mouth, maxillofacial regions, and neck. THe majority (62. 65%) of malignant tumors were located in the nasopharynx which accounted for 28. 68% of all malignanties of which the ratio of mate and female was 3:1, peak age was 41-50 years, 18 of themwas under 10 years of age, the youngest was 1 1/2 years andthe oldest was 84 years old. These data showed that malignant tunors in the head and neck regions, expecially those in the nasopharynx, are common in Guanxi province, China. The program for cancer research on prevention and treatment should be enforced.

MANAGEMENT OF HEAD AND NECK TUMORS

The experience of management of head and neck tumors was summarized by author’s and some other Chinese literatures. This paper mainly introduced the epidemiology, diagnosis, treatment and prognosis of head and neck tumors, especially the malignancies in China. It emphasized that to assign protocols on a case-by-case basis (custom made) and the combined therapy are key points to improve the cure rate or survival rate for head and neck malighancies. Up to now, the 5-year survival rate for squamous cell carcinoma of head and neck was about 62% (1986), and about 71% (1987) for carcinoma of salivary gland origin.

VISUALIZATION OF HEAD AND NECK CANCER MODELS WITH A TRIPLE FUSION REPORTER GENE

The development of experimental animal models for head and neck tumors generally rely on the biol uminescence imaging to achieve the dynamic monitoring of the tumor growth and metastasis due to the complicated anatomical structures.Since the bioluminescence imaging is largely affected by the intracellular luciferase expression level and external D-luciferin concentrations,its imaging accuracy requires further confirmation.Here,a new triple fusion reportelr gene,which consists of a herpes simplex virus type 1 thymidine kinase(TK)gene for radioactive imaging,a far-red fuorescent protein(mLumin)gene for fuorescent imaging,and a firefly luciferase gene for bioluminescence imaging,was introduced for in vrivo observation of the head and neck tumors through multi-modality imaging.Results show that fuorescence and bioluminescence signals from mLumin and luciferase,respectively,were clearly observed in tumor cells,and TK could activate suicide pathway of the cells in the presence of nucleotide analog-ganciclovir(GCV),demonstrating the effecti veness of individual functions of each gene.Moreover,subcutaneous and metastasis animal models for head and neck tumors using the fusion reporter gene-expressing cell lines were established,allowing multi-modality imaging in vio.Together,the established tumor models of head and neck cancer based on the newly developed triple fusion reporter gene are ideal for monitoring tumor growth,assessing the drug therapeutic efficacy and verifying the effec-tiveness of new treatments.

A CLINICAL ANALYSIS OF 7878 PATIENTS WITH TUMORS IN THE HEAD AND NECK

7878 patients with tumors in the head and neck were analyzed in a period of twenty years. All the diagnosis were confirmed by pathologic examination. There were 5485 cases (69.62%) of malignant tumors. Nearly an half of malignant tumors were in the nasopharynx (49.32%). Among the malignant tumors of the nasopharynx, 2698 were carcinoma (99.34%) and only 18 (0.66%) sarcoma. Nine of them were under 10 years of age, the youngest patient was 3 years old, and this is rare in our county. The incidence of head and neck tumors was 37.66% and that of the head and neck malignancies was 26.22% of tumors in the whole body. This study indicates that incidence of malignant tumor in head and neck was rather higher, it is worth to improve ths procedure of treatment and prevention.

Fibroblast activation protein (FAP) as a prognostic biomarker in multiple tumors and its therapeutic potential in head and neck squamous cell carcinoma

Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.

Different imaging techniques in the head and neck:Assets and drawbacks

In this review,the gold standard imaging techniques for the head and neck and the latest upcoming techniques are presented,by comparing computed tomography(CT),magnetic resonance imaging and positron emission tomography-CT,as well as ultrasound,depending on the examined area.The advantages and disadvantages of each examination protocol are presented.This article illustrates the connection between the imaging technique and the examined area.Therefore,the head and neck area is divided into different sections such as bony structures,nervous system,mucous membranes and squamous epithelium,glandular tissue,and lymphatic tissue and vessels.Finally,the latest techniques in the field of head and neck imaging such as multidetector CT,dual-energy CT,flash CT,magnetic resonance angiography,spectroscopy,and diffusion tensor tractography using 3 tesla magnetic resonance are discussed.

Primary Cutaneous Apocrine Carcinoma of the Neck Involving the Parotid Gland: A Case Report and Review of the Literature

Introduction: Primary cutaneous apocrine carcinoma (PCAC) is a rare skin malignant tumor that originates from areas with a high concentration of apocrine glands. The incidence of PCAC in the neck is relatively low. The age of onset in PCAC ranges from 5 to 70 years old. Clinically, PCAC typically shows up as painless nodules or lumps. In immunohistochemistry, positive expression of CK-7, GCDFP-15, AR, and myoepithelial markers are helpful in the diagnosis of PCAC. This case report pertains to a 59-year-old male of Asian descent. Five years ago, a painless mass was discovered behind his right ear, which grew slowly. This patient was identified as PCAC based on clinical symptoms, pathology, immunohistochemistry, and imaging characteristics. PCAC involved the parotid gland in this case;it is easy to be misdiagnosed as a primary malignant tumor of the parotid gland on imaging. Furthermore, a thorough set of clinical, imaging, pathological, and immunohistochemical examinations must be performed to make a diagnosis because it is challenging to differentiate PCAC from metastatic breast carcinoma. Conclusion: A well-developed multidisciplinary examination is essential because PCAC can be challenging to diagnose and differentiate.

基于PANDA模式的护理干预对头颈部肿瘤放疗患者皮损程度及美学效果的影响

目的探讨基于PANDA模式的护理干预对头颈部肿瘤放疗患者皮损程度及美学效果的影响。方法选取2021年9月至2023年12月在南阳市中心医院接受放射性治疗的126例头颈部肿瘤患者为研究对象,按护理方式不同分为观察组和对照组,每组63例。对照组实施放射常规护理,观察组实施基于PANDA模式的护理;比较两组患者放射性皮损分级、放射性皮炎反应评估量表得分、皮损创面愈合时间和美学效果。结果经相应护理干预后,观察组患者放射性皮损分级明显低于对照组,组间比较差异具有统计学意义(Z=3.768,P=0.003)。观察组患者放疗各阶段放射性皮炎反应评估量表得分明显低于对照组,皮损创面愈合时间明显短于对照组,创面愈合百分比明显高于对照组,组间比较差异均具有统计学意义(P<0.05)。观察组患者皮肤永久性红斑、色素沉着、皮肤色泽融合、瘢痕形成等美学评分均优于对照组,组间比较差异具有统计学意义(P<0.05)。结论基于PANDA模式的护理干预能够明显减轻头颈部肿瘤放疗患者皮损程度和放射性皮炎反应,促进皮损创面愈合,提升创面美学效果,值得临床推广应用。

Clinicopathological and Prognostic Significance of Circulating Tumor Cells in Patients with Head and Neck Cancer: A Meta-Analysis

Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.Purpose: The aim of the study was to evaluate the association between clinicopathological and prognostic significance and circulating tumor cells (CTCs) in patients with head and neck cancer. Methods: We searched PubMed, MEDLINE, BioMed, and EMbase databases for studies that assessed the association between clinicopathological and prognostic significance and CTCs in patients with head and neck cancer. Studies obtained from search strategy were screened using pre-specified criteria, and necessary data were retrieved for meta-analysis. Results: Seventeen studies with 816 patients were eligible for combined analysis. Presence of CTCs in peripheral blood was significantly associated with N stage (OR 0.50, 95%CI [0.30, 0.81], n = 10, P = 0.005). Patients in the high-CTC group were significantly associated with poorer disease-free survival (DFS;HR = 1.73, 95%CI [1.01 - 2.96], P = 0.050) and poorer overall survival (OS;HR = 2.53, 95%CI [1.37 - 4.69] P = 0.003). Further analyses indicated strong prognostic powers of CTCs in non-RT-PCR group and pre-treatment group. Conclusion: Our meta-analysis indicates that presence of CTCs is associated with higher N stage and poorer prognosis in patients with head and neck cancer. The potential for further clinical application may be needed for further investigation.

Role of mitophagy in head and neck squamous cell carcinoma:Prognosis and immune insights

Objective:To explore the correlation between mitophagy and the tumor microenvironment(TME)in patients with head and neck squamous cell carcinoma(HNSCC),with an aim to enhance therapeutic efficacy for HNSCC.Methods:A machine learning-based multigene prognostic signature was developed based on mitophagy-related differentially expressed genes(MRGs)identified in The Cancer Genome Atlas cohort.This signature was correlated with the TME using gene set enrichment analysis.The association between this prognostic signature and various immunological features of the TME was explored,including status of tumor-infiltrating immune cells,expression of immune checkpoint molecules,and the immunoscore.Immunohistochemistry validated the expression of hub gene CSNK2A2 and assessed its relationship with immunomarker expression.Quantitative PCR validated CSNK2A2 knockdown in HNSCC cell lines.Functional experiments including Transwell assays to determine cell migration and invasion,Cell Counting Kit 8 assay,and 5-ethynyl-2-deoxyuridine assay were performed to confirm the role of CSNK2A2 in HNSCC.Finally,a subcutaneous xenograft model was generated in C3H mice to validate our findings.Results:The MRG-based prognostic signature showed excellent predictive performance.High-risk patients had significantly shorter progression-free and overall survival(P<0.0001)than low-risk patients.CD8+T cell infiltration was lower in high-risk groups,whereas low-risk groups showed higher immunological marker expression.Thus,the low-risk HNSCC subtype may benefit from immune therapy,while high-risk subtypes may benefit from chemotherapy(P<0.001).CSNK2A2 was highly expressed and strongly correlated with CD8 and PD-L1 based on immunohistochemistry of the HNSCC tissue microarray.CSNK2A2 knockdown reduced cell migration,invasion,and proliferation,and arrested cells in G1 phase.In vivo,it led to slower tumor growth and smaller tumor volumes.Conclusion:We established a potential prognostic signature that could improve HNSCC management in the future.CSNK2A2 may be a new biomarker to predict immunotherapy efficacy in HNSCC.