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Background: Cell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear. Methods: Data from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model. Results: T cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10 , DDX19A , NDFIP1 , PCMT1 , HPRT1 , SLC2A3 , EFNB2 , HK1 , BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription. Conclusion: The CDRscore model could be utilized as a powerful prognostic indicator for HNC. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early‐stage HNC. For recurrent or metastatic (R/M) HNC, the first‐line treatment is platinum‐based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody–drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC. [ABSTRACT FROM AUTHOR]

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to figure out the potential role of exosomal microRNAs, and their targeted genes in HNC detection/diagnosis. Methods: In the present study, exosomes were extracted from the serum samples of 400 HNC patients and 400 healthy controls. Exosomes were characterized using TEM, NTA, TEM-immunogold labeling and ELISA. Quantitative PCR was used to measure the expression level of exosomal miRNA-19a, miRNA-19b and targeted genes SMAD2 and SMAD4 in HNC patients and controls. Results: The deregulation of miR-19a (p < 0.01), miR-19b (p < 0.03), SMAD2 (p < 0.04) and SMAD4 (p < 0.04) was observed in HNC patients vs controls. Conclusion: ROC curve and Kaplan–Meier analysis showed the good diagnostic/prognostic value of selected exosomal microRNAs and related genes in HNC patients. Article highlights Mostly tumor cells release an increased quantity of exosomes and have been reported linked with the aggressiveness of different cancers including head and neck cancer (HNC). Exosomes are extracellular vesicles with 40–160 nm diameter and play a role in the transfer of cargo materials like protein, RNAs (including miRNAs) and DNA. However, the role of serum exosomes shuttled RNAs and miRNAs in HNC remains unclear. The current study is designed to find out the diagnostic/prognostic values of exosomal miR-19a, miR-19b, SMAD2 and SMAD4 in HNC patients vs healthy controls. Exosomes were extracted from the 400 serum samples of HNC as compared with age- and gender-matched 400 healthy controls. The morphology, size distribution and concentration of extracted exosomes were confirmed through transmission electron microscopy, NTA and ELISA. Relative expression of exosomal miR-19a and miR-19b was significantly downregulated in HNC patients compared with controls. Significant upregulation of SMAD2 and SMAD4 expression was observed in serum exosomes of HNC patients compared with controls. According to survival analysis, exosomal miR-19a, miR-19b, SMAD2 and SMAD4 deregulation lead significantly correlated with decreased survival of HNC patients. Univariant and multivariant Cox regression analysis showed that deregulation of exosomal miR-19a, miR-19b, SMAD2 and SMAD4 was found as independent prognostic factors in HNC patients. Receiver operating characteristic curve analysis showed a good diagnostic value of selected exosomal markers in HNC patients. [ABSTRACT FROM AUTHOR]

Increased serum lactate dehydrogenase (LDH) activity is considered as a marker of cellular necrosis and serves as a metabolomic diagnostic marker in several types of cancer including head and neck squamous cell carcinoma (HNSCC). LDH, an enzyme involved in the glycolytic cycle, is correlated not only with the activation of oncogenes such as HIF-α and Myc, but also with effects such as tumor proliferation and metastasis. Serum alkaline phosphatase (ALP) is a marker of cell differentiation and tumor induction. Albumin-to-alkaline phosphatase ratio (AAPR) could be an advantageous biomarker due to its easily accessible dynamics and cost-effectiveness. Elevated values of AAPR could be associated with longer overall survival (OS) in cases with solid tumors. Diabetes mellitus (DM) could influence the outcome of patients with HNSCC by contributing to insulin resistance and chronic inflammation, and by being involved in various aspects of carcinogenesis, disease progression and metastasis. However, the use of antihyperglycemic medications (metformin) can have beneficial effects by inhibiting tumor metabolic pathways. The biomarker role of LDH and AAPR in HNSCC patients with DM has been less evaluated. The purpose of the study was to assess the prognostic value of pretreatment serum lactate dehydrogenase (LDH) and albumin-to-alkaline phosphatase ratio (AAPR) in predicting the duration of non-surgical oncological treatment and glycemic control in cases of head and neck cancers patients with DM, including cases selected from the database of the oncology clinic and oncology outpatient clinic of the Craiova County Hospital. Both LDH and AAPR can be used as pre-treatment biomarkers predictive of treatment response, or prognostic tools included in complex multi-parametric models in HNC associated with DM. However, given the impact of short-term glycemic control on the LDH level, it is necessary to evaluate these biomarkers after assessing and controlling for DM, and with the recommended cut-off value set around 0.5. Due to the limited number of cases, it is necessary to validate the results in multicentric trials with a larger number of patients (Tab. 5, Ref. 50). Text in PDF www.elis.sk [ABSTRACT FROM AUTHOR]

Background: Superficial lobe constitutes 80% of the parotid and is situated lateral to mandible and can be better spared during intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC). This study aimed to see the impact of bilateral superficial parotid gland (PG) sparing IMRT on xerostomia and quality of life (QOL) in patients with HNC receiving radiation. Study Design: Prospective, questionnaire-based study. Materials and Methods: Thirty-four patients with histopathologically proven non-nasopharyngeal non-oral cavity HNC were included in this study. IMRT technique was used and a constraint of 24 Gy was given to combined superficial PG. Physician- and patient-rated xerostomia and QOL scores were recorded at baseline and two weeks, three months, and six months post-radiation therapy (RT). The combined superficial PG dose correlated with xerostomia and QOL scores. Results: The combined superficial PG and combined whole PG mean dose was 18.71 Gy and 30 Gy, respectively, and the difference was statistically significant (P -< 0.001). At two weeks, three months, and six months post-RT, the odds of xerostomia scores were 0.11, 0.071, 0.042, respectively for a median dose of <18 Gy compared to >18 Gy and was statistically significant P =(0.001). Conclusion: Bilateral superficial PG sparing IMRT is beneficial in reducing xerostomia and translates to a better QOL. [ABSTRACT FROM AUTHOR]

BackgroundCell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear.MethodsData from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model.ResultsT cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10, DDX19A, NDFIP1, PCMT1, HPRT1, SLC2A3, EFNB2, HK1, BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription.ConclusionThe CDRscore model could be utilized as a powerful prognostic indicator for HNC.

Abstract Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early‐stage HNC. For recurrent or metastatic (R/M) HNC, the first‐line treatment is platinum‐based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody–drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.

Simple Summary: Head and neck squamous cell carcinoma is one of the most common cancers that arises in the upper aerodigestive tract. Patients suffering from this cancer have a high mortality risk, mainly due to local recurrence, resistance to chemo- and radiotherapy, and metastasis. The more aggressive behavior of this tumor is associated with epithelial–mesenchymal transition, a process described in both physiological, primarily during embryonic development, and pathological situations, including the progression of other types of tumors. Epithelial-to-mesenchymal transition is governed by various transcription factors that regulate target gene expression and play a role in the resistance to contemporary head and neck cancer therapies. This review presents the current knowledge of the main transcription factors involved in mesenchymal conversion and discusses their role in head and neck squamous cell carcinoma treatment. The main protein markers associated with this cancer type are also presented. Head and neck cancers (HNCs) are heterogeneous and aggressive tumors of the upper aerodigestive tract. Although various histological types exist, the most common is squamous cell carcinoma (HNSCC). The incidence of HNSCC is increasing, making it an important public health concern. Tumor resistance to contemporary treatments, namely, chemo- and radiotherapy, and the recurrence of the primary tumor after its surgical removal cause huge problems for patients. Despite recent improvements in these treatments, the 5-year survival rate is still relatively low. HNSCCs may develop local lymph node metastases and, in the most advanced cases, also distant metastases. A key process associated with tumor progression and metastasis is epithelial–mesenchymal transition (EMT), when poorly motile epithelial tumor cells acquire motile mesenchymal characteristics. These transition cells can invade different adjacent tissues and finally form metastases. EMT is governed by various transcription factors, including the best-characterized TWIST1 and TWIST2, SNAIL, SLUG, ZEB1, and ZEB2. Here, we highlight the current knowledge of the process of EMT in HNSCC and present the main protein markers associated with it. This review focuses on the transcription factors related to EMT and emphasizes their role in the resistance of HNSCC to current chemo- and radiotherapies. Understanding the role of EMT and the precise molecular mechanisms involved in this process may help with the development of novel anti-cancer therapies for this type of tumor. [ABSTRACT FROM AUTHOR]

Background: Facemasks accurately immobilise patients with head and neck cancer (HNC) receiving radiotherapy (RT). However, such masks are associated with treatment related distress, a prognostic factor for poorer survival. Open masks offer increased comfort and patient satisfaction. We investigated whether open masks could immobilise patients without affecting treatment accuracy. Materials and methods: Over an 18-month period, all HNC RT patients with anxiety were offered open masks. Once 30 patients had completed treatment, set-up data was compared to patients in closed masks. The mean displacement and one-dimensional standard deviations (SD) of the mean, systematic and random set-up errors were calculated for translational directions: anterior-posterior (x), superior-inferior (y), medial-lateral (z). The mean and SD of the mean was calculated for rotational displacements. Mann-Whitney U was used to determine any significant differences between set- up data. Results: Sixty patients were included (30 open & 30 closed masks). There was no statistically significant difference found in the x (p = 0.701), y (p = 0.246) or z (p = 0.535) direction for the SD of the mean displacements between both masks. No statistically significant difference was found in the SD of means for rotational displacements. The calculated planning target volume (PTV) margin requirements were minimally less for the closed masks 3.5, 2.6, and 2.7 mm (x, y, z, respectively) versus 4.2, 3.2, and 3.7 mm, respectively, for open masks. Conclusion: Our study demonstrates that open masks maintain accuracy at levels comparable to closed masks in patients with anxiety. The minor difference in the calculated PTV margin could be rectified with daily on-line imaging or surface guided imaging. [ABSTRACT FROM AUTHOR]

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches.

Background and Objectives: The rate of head and neck cancer (HNC) is expected to increase by 30% by 2030. However, there are many similarities between the symptomatology of a benign and a malign diagnosis; thus, a protocol for conducting a full head and neck examination is of high importance since the absence of adenopathy does not exclude a malignant diagnosis and also a favorable prognosis. Material and methods: The current study presents a retrospective study on 515 adult patients who underwent a biopsy for possible head and neck tumor pathology. Results: The patients identified with cancer were older than the rest of the group, with a higher developing trend in men than in women. However, the top 10 symptomatology patterns were identical in the malign and benign groups, meaning that new HNC may be missed due to the common symptomatology between benign and malign outcomes. Conclusions: The importance of a full ear, nose, and throat (ENT) examination may be of significant relevance for a proper diagnosis that can improve the overall prognosis of a patient with cancer. The absence of routine screening tests and screening guidelines for oral and pharyngeal cancers represents a significant barrier to secondary HNC prevention.

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

Introduction: Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and pallets-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors, including head and neck cancers (HNC). The purpose of the study: To evaluate the possible purposes and biomarker value of NLR, PLR, and MLR recorded pre-treatment (radiotherapy/chemotherapy) in HNC. Materials and methods: From 190 patients with HNC included in the oncology records in the oncology outpatient clinic of the Craiova County Emergency Hospital (from January 2002 to December 2022), 39 cases met the inclusion criteria (squamous cell carcinoma and the possibility to calculate the pre-treatment (chemotherapy/radiotherapy) value of NLR, PLR, and MLR. Overall survival (OS) values were correlated with NLR, PLR, and MLR. Results: The median values for NLR, PLR, and MLR were 6.15 (1.24–69), 200.79 (61.3–1775.0), and 0.53 (0.12–5.5), respectively. In the study, the mean values for NLR, PLR, and MLR of 2.88, 142.97, and 0.36, respectively, were obtained. The median OS in the study group was 11 months (1–120). Although a negative Pearson's correlation was present, the relationship between the variables was only weak, with values of R = 0.07, p = 0.67, R = 0.02, p = 0.31, and R = 0.07, p = 0.62 being related to NLR, PLR, and MLR, respectively, in correlation with OS. The median values of NLR, PLR, and MLR were calculated (1.53, 90.32, and 0.18, respectively) for the HNC cases with pre-treatment values of NLR < 2 and for the HNC cases with NLR values ≥ 6 (23.5, 232.78, and 0.79, respectively). The median OS for cases with NLR < 2 and NLR ≥ 6 were 17.4 and 13 months, respectively. Conclusions: The comparative analysis of the data highlights a benefit to OS for cases low values of NLR. The role of not only borderline NLR values (between 2 and 6) as a prognostic marker in HNSCC but also the inclusion of PLR and MLR in a prognostic score must also be defined in the future. Prospective studies with more uniformly selected inclusion criteria could demonstrate the value of pre-treatment NLR, PLR, and MLR for treatment stratification through the intensification or de-escalation of non-surgical curative treatment in HNSCC. [ABSTRACT FROM AUTHOR]

Th e incidence of human papillomavirus (HPV)-associated head and neck cancer (HNC) has been rapidly increasing in developed countries, with HPV-associated HNC now accounting for 70% of all HNC cases. An increased incidence has been noted particularly among males. Th e disparities in HPV vaccine uptake rates and the increasing number of individuals with HPV-associated HNC suggest a lack of public awareness of both HPV sequelae and prevention options. Th is review highlights the importance of prophylactic HPV vaccination for preventing HPV-associated HNC, particularly in males. Current evidence substantiates the need for gender-neutral HPV vaccination programs and reinforces the recommendations made by the CDC. Th is article raises awareness of the association between HPV and HNC as well as the eff ectiveness of HPV vaccination in HNC prevention. [ABSTRACT FROM AUTHOR]

Background and Objectives: The rate of head and neck cancer (HNC) is expected to increase by 30% by 2030. However, there are many similarities between the symptomatology of a benign and a malign diagnosis; thus, a protocol for conducting a full head and neck examination is of high importance since the absence of adenopathy does not exclude a malignant diagnosis and also a favorable prognosis. Material and methods: The current study presents a retrospective study on 515 adult patients who underwent a biopsy for possible head and neck tumor pathology. Results: The patients identified with cancer were older than the rest of the group, with a higher developing trend in men than in women. However, the top 10 symptomatology patterns were identical in the malign and benign groups, meaning that new HNC may be missed due to the common symptomatology between benign and malign outcomes. Conclusions: The importance of a full ear, nose, and throat (ENT) examination may be of significant relevance for a proper diagnosis that can improve the overall prognosis of a patient with cancer. The absence of routine screening tests and screening guidelines for oral and pharyngeal cancers represents a significant barrier to secondary HNC prevention. [ABSTRACT FROM AUTHOR]

Purpose: PET-derived metabolic tumor volume (MTV) and total lesion glycolysis of the primary tumor are known to be prognostic of clinical outcome in head and neck cancer (HNC). Including evaluation of lymph node metastases can further increase the prognostic value of PET but accurate manual delineation and classification of all lesions is time-consuming and prone to interobserver variability. Our goal, therefore, was development and evaluation of an automated tool for MTV delineation/classification of primary tumor and lymph node metastases in PET/CT investigations of HNC patients. Methods: Automated lesion delineation was performed with a residual 3D U-Net convolutional neural network (CNN) incorporating a multi-head self-attention block. 698 [ 18 F]FDG PET/CT scans from 3 different sites and 5 public databases were used for network training and testing. An external dataset of 181 [ 18 F]FDG PET/CT scans from 2 additional sites was employed to assess the generalizability of the network. In these data, primary tumor and lymph node (LN) metastases were interactively delineated and labeled by two experienced physicians. Performance of the trained network models was assessed by 5-fold cross-validation in the main dataset and by pooling results from the 5 developed models in the external dataset. The Dice similarity coefficient (DSC) for individual delineation tasks and the primary tumor/metastasis classification accuracy were used as evaluation metrics. Additionally, a survival analysis using univariate Cox regression was performed comparing achieved group separation for manual and automated delineation, respectively. Results: In the cross-validation experiment, delineation of all malignant lesions with the trained U-Net models achieves DSC of 0.885, 0.805, and 0.870 for primary tumor, LN metastases, and the union of both, respectively. In external testing, the DSC reaches 0.850, 0.724, and 0.823 for primary tumor, LN metastases, and the union of both, respectively. The voxel classification accuracy was 98.0% and 97.9% in cross-validation and external data, respectively. Univariate Cox analysis in the cross-validation and the external testing reveals that manually and automatically derived total MTVs are both highly prognostic with respect to overall survival, yielding essentially identical hazard ratios (HR) ( HR man = 1.9 ; p < 0.001 vs. HR cnn = 1.8 ; p < 0.001 in cross-validation and HR man = 1.8 ; p = 0.011 vs. HR cnn = 1.9 ; p = 0.004 in external testing). Conclusion: To the best of our knowledge, this work presents the first CNN model for successful MTV delineation and lesion classification in HNC. In the vast majority of patients, the network performs satisfactory delineation and classification of primary tumor and lymph node metastases and only rarely requires more than minimal manual correction. It is thus able to massively facilitate study data evaluation in large patient groups and also does have clear potential for supervised clinical application. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is a prevalent and diverse group of malignancies with substantial morbidity and mortality rates. Early detection and monitoring of HNC are crucial for improving patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, has emerged as a promising tool for cancer detection and monitoring. In this article, we review the application of RNA-based liquid biopsy in HNC. Various types of RNA, including messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), circular RNA (circRNA) and PIWI-interacting RNA (piRNA), are explored as potential biomarkers in HNC liquid-based diagnostics. The roles of RNAs in HNC diagnosis, metastasis, tumor resistance to radio and chemotherapy, and overall prognosis are discussed. RNA-based liquid biopsy holds great promise for the early detection, prognosis, and personalized treatment of HNC. Further research and validation are necessary to translate these findings into clinical practice and improve patient outcomes. [ABSTRACT FROM AUTHOR]

IntroductionHead and neck carcinoma (HNC) is a disease with a poor prognosis despite currently available treatments. The management of patients with this tumor is often complicated by several comorbidities. Among these, diabetes is the second most frequent and its influence on the prognosis is not known.MethodsIn this work, we collected data on progression free survival (PFS) and overall survival (OS) of one hundred twenty-three patients with HNC who received biweekly cetuximab maintenance treatment after first-line chemotherapy. We then compared the survival of nondiabetic patients versus diabetics’ one.ResultsSurprisingly, both PFS (4 vs. 5 months, HR 2.297, p

The aim of the present study was to employ CELLSEARCH® technology for the detection of circulating tumor cells (CTCs) in the peripheral blood of head and neck cancer (HNC) patients, and to assess the association between CTC count and patient prognosis. In this retrospective study, a cohort of 56 patients diagnosed with HNC and receiving treatment at the Department of Otolaryngology, Head and Neck Surgery (Beijing Tongren Hospital) between December 2013 and June 2018 were selected. Utilizing CELLSEARCH® technology, the presence of CTCs were detected in samples of peripheral blood from patients with head and neck cancer (HNC) patients, and CTC counts were documented. CTC positivity was defined as CTCs ≥1/7.5 ml of peripheral blood. Comprehensive data encompassing general demographic profiles, pathological classifications, tumor node metastasis (TNM) staging, tumor histology and treatment modalities were gathered for each participant. The study employed the Kaplan-Meier method to scrutinize and compare survival rates between CTC-positive and CTC-negative cohorts, while both univariate and multivariate Cox regression analyses were conducted to discern the factors impacting the overall survival (OS) of individuals diagnosed with HNC. Out of the 56 patients examined, 14 individuals exhibited detectable levels of CTCs, resulting in a positivity rate of 25%. The analysis revealed a significant association between the levels of CTCs in patients with HNC and the utilization of non-surgical treatment (P<0.05), while no substantial associations were observed concerning sex, age, smoking habits, alcohol consumption, pathological classifications, TNM staging, tumor attributes and surgical interventions (all P>0.05). Survival analysis revealed a reduction in the OS among patients with HNC harboring CTC positivity in contrast to their CTC-negative counterparts. The comprehensive multivariate Cox regression analysis underscored the independent prognostic impact of CTC presence (HR=1.274; 95% CI, 1.119–1.451; P<0.001) and the implementation of non-surgical treatment (HR=0.268; 95% CI, 0.119–0.607; P=0.002) on the prognosis of individuals grappling with HNC. In conclusion, the levels of CTCs were an independent factor affecting outcomes in patients with HNC, with CTC-positive patients showing significantly shorter survival compared with CTC-negative cases. [ABSTRACT FROM AUTHOR]

Head and neck cancers (HNC) are a heterogeneous group of tumours mainly associated with tobacco and alcohol use and human papillomavirus (HPV). Over 90% of all HNC are squamous cell carcinomas (HNSCC). Sample material from patients diagnosed with primary HNSCC (n = 76) treated with surgery as primary treatment at a single centre were assessed for HPV genotype, miR-9-5p, miR-21-3p, miR-29a-3p and miR-100-5p expression levels. Clinical and pathological data were collected from medical records. Patients were enrolled between 2015 and 2019 and followed-up until November 2022. Overall survival, disease-specific survival and disease-free survival were assessed and correlated with clinical, pathological, and molecular data. Kaplan-Meier and Cox proportional hazard regression was used to assess different risk factors. In the study, male gender, HPV-negative HNSCC (76.3%) mostly located in the oral region (78.9%) predominated. Most patients had stage IV cancer (47.4%), and the overall survival rate was 50%. HPV was found not to affect survival, indicating that in this population, classic risk factors predominate. The presence of both perineural and angioinvasion was strongly associated with survival in all analyses. Of all miRNAs assessed, only upregulation of miR-21 was consistently shown to be an independent predictor of poor prognosis and may thus serve as a prognostic biomarker in HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: Human papillomavirus (HPV) mediated oropharyngeal cancer (OPC) incidence has increased dramatically. Accurate oral HPV prevalence data are essential for assessing population epidemiology, vaccination and screening programmes. As oral rinse is the most commonly used primary outcome measure for estimating oral HPV prevalence, we aimed to compare the efficacy of oral rinse against other detection methods., Methods: The Oromouth study enrolled 945 participants, aged 0-65 years (63% female), undergoing tonsillectomy for non-malignant indications, without OPC diagnoses. Samples from oral rinse, pharyngeal wall, tongue base, tonsil tissue and blood were collected. HPV DNA in oral samples was centrally tested via polymerase chain reaction, and serology samples for HPV antibodies. Statistical analyses assessed prevalence, detection rates and ratios., Results: Combining all four oral collection sites, high-risk (HR)-HPV and any HPV prevalence were 4·3% and 18%, respectively. HR-HPV prevalence was similar between males (4·1%) and females (4·5%). Oral rinse had the highest HR-HPV (4·0%) and any HPV detection rates (16%), but still missed 73% (11/15) identified as HR-HPV-positive by other oral sites. Compared to oral rinse alone, an additional 38% (11/29) HR-HPV infections were picked up by the other three oral collection methods. Addition of serology testing did not result in substantial improvement., Conclusions: Of the four oral sites, oral rinse demonstrates the highest detection rates by far but has important limitations. These findings should be taken into consideration when estimating oral HPV infection rates, especially for vaccination studies and screening programmes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All other authors received no personal funding and have declared that no competing interests exist., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an increasing trend of its incidence. Alcohol consumption, smoking, and viral infections, such as the mucosal high-risk (HR) human papillomaviruses (HPVs) are major risk factors for HNSCC development. In particular, HR HPVs are mainly associated with a subset of oropharyngeal squamous cell carcinoma (OPSCC), while other head and neck sites are marginally affected by HPV infection. HPV16 is the most frequently HR HPV type associated with HNSCC. In contrast to the cervix, no screening programs or identifiable pre-malignant lesions have been characterized for HPV-related HNSCC. Therefore, identification of general diagnostic algorithms and HPV biomarkers that could facilitate the early diagnosis, disease evolution and recurrence for HPV-driven HNSCCs are urgently needed. We herein review the role of HPV in HNSCC with a focus on epidemiology, biology, applied diagnostic algorithms and available biomarkers in body fluids as early diagnostic tools in HPV-driven HNSCCs.

Capecitabine, an oral pro-drug that is metabolized to 5-FU, has been used in clinical practice for more than 20 years, being part of the therapeutic standard for digestive and breast cancers. The use of capecitabine has been evaluated in many trials including cases diagnosed in recurrent or metastatic settings. Induction regimens or a combination with radiation therapy were evaluated in head and neck cancers, but 5-FU still remained the fluoropyrimidine used as a part of the current therapeutic standard. Quantifications of levels or ratios for enzymes are involved in the capecitabine metabolism to 5-FU but are also involved in its conversion and elimination that may lead to discontinuation, dose reduction or escalation of treatment in order to obtain the best therapeutic ratio. These strategies based on biomarkers may be relevant in the context of the implementation of precision oncology. In particular for head and neck cancers, the identification of biomarkers to select possible cases of severe toxicity requiring discontinuation of treatment, including "multi-omics" approaches, evaluate not only serological biomarkers, but also miRNAs, imaging and radiomics which will ensure capecitabine a role in both induction and concomitant or even adjuvant and palliative settings. An approach including routine testing of dihydropyrimidine dehydrogenase (DPD) or even the thymidine phosphorylase (TP)/DPD ratio and the inclusion of miRNAs, imaging and radiomics parameters in multi-omics models will help implement "precision chemotherapy" in HNC, a concept supported by the importance of avoiding interruptions or treatment delays in this type of cancer. The chemosensitivity and prognostic features of HPV-OPC cancers open new horizons for the use of capecitabine in heavily pretreated metastatic cases. Vorinostat and lapatinib are agents that can be associated with capecitabine in future clinical trials to increase the therapeutic ratio. [ABSTRACT FROM AUTHOR]

Aim: The present study was designed to evaluate the role of DNA damage response pathway genes and heat-shock proteins in head and neck cancer (HNC) risk. Methods: For this purpose, two study cohorts were used. Cohort 1 (blood samples of 250 HNC patients and 250 controls) was used for polymorphism screening of selected genes using tetra-primer amplification refractory mutation system-polymerase chain (Tetra-ARMS PCR). Cohort 2 (200 HNC tumors and adjacent controls) was used for expression analysis, using quantitative PCR. Results: Analysis showed that mutant allele frequency of selected polymorphisms was found associated with increased HNC risk. Expression analysis showed the significant deregulation of selected genes in patients. Conclusion: The present study showed that selected genes (CHK1, CHK2, HSP70 and HSP90) can act as good diagnostic/prognostic markers in HNC. The present study is designed to identify the selected genes of DNA damage response pathway and heat-shock proteins as diagnostic/prognostic markers of head and neck cancer (HNC). To do this, DNA was isolated from blood samples and RNA isolated from the tissue samples of HNC patients. The mutation and expression level of selected genes was tested, and selected genes showed good diagnostic/prognostic values for HNC patients. [ABSTRACT FROM AUTHOR]

Brilliant urban communities, gridlock, squander the board, primary well being, security, crisis administrations, coordination, retail, modern control, and medical care are only a couple of the applications that the Internet of Things can assist with. The Internet of Things is a super innovation that can associate with anything, anyone, whenever, spot, stage, and organization. It fundamentally affects the whole square chain of ventures, savvy items and gadgets, frameworks and administrations given by heterogeneous organization association, and is being created as a brilliant inescapable structure for shrewd gadgets. Since gadgets connect to confounded gear, collaborate with threatening environmental elements, and are sent on an assortment of unregulated stages, they defy a few security dangers and difficulties. Since the Internet of Things has the ability to coordinate any kind of organization or modern framework, it could be powerless against weaknesses innate in the different frameworks that make up the incorporated organization. The reason for this exploration paper is to examine the security gives that singular framework answerable for interconnection face, just as their effect on the in general framework.

Trismus is a potentially critical morbidity following curative-intended radiotherapy in head and neck cancer patients. However, in this setting, evidence regarding this side effect remains to be fully defined, particularly in terms of dosimetric parameters. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of the evidence on radiation-induced trismus in the literature, particularly the dosimetric concerns. The treatment goal should be to maintain high cure rates and limit the onset of complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring. • Radiotherapy is a mainstay of treatment for head and neck cancer. • Trismus is a detrimental radiation-induced side-effect. • Evidence regarding trismus clinical/dosimetric predictors is still scant. • Dedicated evaluations are eagerly awaited to target treatment tailoring. [ABSTRACT FROM AUTHOR]

Mechanistic research suggests a unique evolutionary relationship between complex milk oligosaccharides and cognate bifidobacteria enriched in breast-fed infants. Bovine milk oligosaccharides (BMO) were recently identified as structurally and functionally similar to human milk oligosaccharides. The present single-blind three-way crossover study is the first to determine the safety and tolerability of BMO consumption by healthy human participants (n 12) and its effects on faecal microbiota and microbial metabolism. Participants consumed each supplement (placebo-control; low- and high-BMO doses) for eleven consecutive days, followed by a 2-week washout period prior to initiating the next supplement arm. Low and high BMO doses were consumed as 25 and 35 % of each individual's daily fibre intake, respectively. Safety and tolerability were measured using standardised questionnaires on gut and stomach discomfort and stool consistency. Faecal extracts were profiled for bacterial populations by next-generation sequencing (NGS) and bifidobacteria presence was confirmed using quantitative PCR. Urine was analysed for changes in microbial metabolism using nuclear magnetic resonance spectroscopy (1H-NMR). Consumption of both the low and high BMO doses was well tolerated and did not change stool consistency from baseline. Multivariate analysis of the NGS results demonstrated no change in faecal microbiota phyla among the placebo-control and BMO supplement groups. In conclusion, BMO supplementation was well tolerated in healthy adults and has the potential to shift faecal microbiota toward beneficial strains as part of a synbiotic treatment with probiotic cultures that selectively metabolise oligosaccharides.

Background: The sarcomatoid variant of squamous cell carcinoma (SCC) is an uncommon variant of head-and-neck cancer with a clinically aggressive course and poor outcomes. The data on the clinical presentation and pattern of treatment received by patients with sarcomatoid variant of SCC are scarce. Objectives: In this study, we aimed to assess the clinical presentation, intent of treatment, and the subsequent treatment-related outcomes of patients with sarcomatoid variant of SCC of the head-and-neck region. Materials and Methods: This retrospective study was conducted among treatment-naïve patients with sarcomatoid variant of SCC of the head-and-neck region who presented to the Tata Memorial Center, a tertiary care center, in Mumbai, India, between January 2012 and December 2018. The primary objective was to evaluate the stage at presentation and the intent of treatment received. The secondary outcome was disease-free survival (DFS). Variables were analyzed using simple descriptive statistical methods. DFS was calculated using the Kaplan–Meier method. Results: A total of 60 patients with sarcomatoid variant of SCC were included in the study. The median age of the patients was 51 years, with a male-to-female ratio of 5:1. The oral cavity was the most common subsite, reported in 39 (65%) patients. A total of 43 (71.6%) patients presented with advanced-stage disease, and 41 (68.3%) received curative-intent treatment. The DFS of patients who received curative treatment was 76.3 months (95% confidence interval [CI], 60.3–92.4) and that of patients who received palliative-intent treatment was 11.6 months (95% CI, 9.2–14). Conclusions: Sarcomatoid variant of SCC of the head-and-neck region usually presents with advanced-stage disease, however, has a reasonable DFS when treated appropriately with curative intent.

Purpose: This study sought to identify circular RNAs (circRNA) that participate in the regulation of head and neck cancer (HNC), analyze their clinical application, and predict their molecular mechanism during HNC. Materials and Methods: High-throughput sequencing was used to analyze circRNA expression in 18 matched HNC and adjacent normal tissues. Target circRNAs with significantly differential expression were obtained. In 103 HNC and adjacent normal tissues, real-time fluorescent quantitative PCR (qRT-PCR) was used to verify the differential expression of target circRNAs. This data was combined with clinicopathological information to analyze the diagnostic value of target circRNA. Bioinformatics was used to find target circRNAs that acted as competitive endogenous RNA (ceRNA) and construct a circRNA-miRNA-mRNA regulatory network. mRNA expression was verified by immunohistochemistry (IHC). Results: A total of 714 differentially expressed circRNAs were detected in HNC, and the low expression of hsa_circ_0001675 was particularly significant (fold change [FC] = -4.85, P = 6.305E-05). hsa_circ_0001675 had significantly lower expression in HNC than in normal tissue (P < 0.01). Low hsa_circ_0001675 expression was positively associated with tumor invasion and clinical staging (P < 0.05), and its area under the ROC curve (AUC) was 0.7776. Low hsa_circ_0001675 expression also correlated with the overall survival (OS) rate and the progression-free survival (PFS) rate of HNC patients (P < 0.001). Bioinformatics was used to construct a ceRNA network of hsa_circ_0001675 with six differentially expressed miRNAs (hsa-miR-330-5p, hsa-miR-498, hsa-miR-532-3p, hsa-miR-577, hsa-miR-1248, and hsa-miR-1305) and 411 differentially expressed mRNAs and found that the neuroactive ligand-receptor interaction, and the cAMP and calcium signaling pathways were particularly enriched. Further bioinformatics and IHC analysis showed that miR577/TESC is the likely downstream signaling pathway for hsa_circ_0001675. Conclusion: This study showed that hsa_circ_0001675 is downregulated in HNC and could be an effective biomarker for HNC diagnosis. In addition, hsa_circ_0001675 may have a potential ceRNA mechanism and suppress HNC disease progression through the hsa_circ_0001675-miRNA-mRNA axis. [ABSTRACT FROM AUTHOR]

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.

Abstract Inflammation response of epithelial mucosa to chemo- radiotherapy cytotoxic effects leads to mucositis, a painful side effect of antineoplastic treatments. About 40% of the patients treated with chemotherapy develop mucositis; this percentage rises to about 90% for head and neck cancer patients (HNC) treated with both chemo- and radiotherapy. 19% of the latter will be hospitalized and will experience a delay in antineoplastic treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis and an increase in patient management costs. Currently, several interventions and prevention guidelines are available, but their effectiveness is uncertain. This review comprehensively describes mucositis, debating the impact of standard chemo-radiotherapy and targeted therapy on mucositis development and pointing out the limits and the benefits of current mucositis treatment strategies and assessment guidelines. Moreover, the review critically examines the feasibility of the existing biomarkers to predict patient risk of developing oral mucositis and their role in early diagnosis. Despite the expression levels of some proteins involved in the inflammation response, such as TNF-α or IL-1β, partially correlate with mucositis process, their presence does not exclude others mucositis-independent inflammation events. This strongly suggests the need to discover biomarkers that specifically feature mucositis process development. Non-coding RNAs might hold this potential.

PurposeThis study sought to identify circular RNAs (circRNA) that participate in the regulation of head and neck cancer (HNC), analyze their clinical application, and predict their molecular mechanism during HNC.Materials and MethodsHigh-throughput sequencing was used to analyze circRNA expression in 18 matched HNC and adjacent normal tissues. Target circRNAs with significantly differential expression were obtained. In 103 HNC and adjacent normal tissues, real-time fluorescent quantitative PCR (qRT-PCR) was used to verify the differential expression of target circRNAs. This data was combined with clinicopathological information to analyze the diagnostic value of target circRNA. Bioinformatics was used to find target circRNAs that acted as competitive endogenous RNA (ceRNA) and construct a circRNA-miRNA-mRNA regulatory network. mRNA expression was verified by immunohistochemistry (IHC).ResultsA total of 714 differentially expressed circRNAs were detected in HNC, and the low expression of hsa_circ_0001675 was particularly significant (fold change [FC] = -4.85, P = 6.305E-05). hsa_circ_0001675 had significantly lower expression in HNC than in normal tissue (P < 0.01). Low hsa_circ_0001675 expression was positively associated with tumor invasion and clinical staging (P < 0.05), and its area under the ROC curve (AUC) was 0.7776. Low hsa_circ_0001675 expression also correlated with the overall survival (OS) rate and the progression-free survival (PFS) rate of HNC patients (P < 0.001). Bioinformatics was used to construct a ceRNA network of hsa_circ_0001675 with six differentially expressed miRNAs (hsa-miR-330-5p, hsa-miR-498, hsa-miR-532-3p, hsa-miR-577, hsa-miR-1248, and hsa-miR-1305) and 411 differentially expressed mRNAs and found that the neuroactive ligand-receptor interaction, and the cAMP and calcium signaling pathways were particularly enriched. Further bioinformatics and IHC analysis showed that miR577/TESC is the likely downstream signaling pathway for hsa_circ_0001675.ConclusionThis study showed that hsa_circ_0001675 is downregulated in HNC and could be an effective biomarker for HNC diagnosis. In addition, hsa_circ_0001675 may have a potential ceRNA mechanism and suppress HNC disease progression through the hsa_circ_0001675-miRNA-mRNA axis.

The aim of this study was to translate the Liverpool Oral Rehabilitation Questionnaire version 3 (LORQv3) into German and validate this version in order to assess oral-health-related quality of life (OHRQoL) among head and neck cancer patients. This study was conducted at a German university clinic among patients who had completed therapy for squamous cell carcinoma of the head and neck (HNSCC). The original English-language LORQv3 was translated into German according to the forward–backward approach. Validity and reliability were evaluated using further questionnaires related to OHRQoL and psychological impairments. Subgroups were built with reference to oral rehabilitation status and type of cancer therapy. Furthermore, OHRQoL was evaluated. Test–retest reliability was assessed by weighted kappa with a 10–14 day interval. Data were analysed by using Spearman's correlation and the following tests: Shapiro–Wilk, Kruskal–Wallis, Mann–Whitney U and Cronbach's alpha. The level of significance was set at α = 0.05. Analysis of the LORQv3 evaluations revealed excellent Cronbach's alpha and high test–retest reliability. Construct validity were supported by the data. LORQv3 summary score and domains were significantly affected by status of oral rehabilitation (p = 0.003, p = 0.008, p = 0.024) and treatment approach (p < 0.001, p = 0.025, p = 0.035). The German version of the LORQv3 showed high reliability and validity and an impaired OHRQoL of HNSCC patients. It can therefore be recommended for the assessment of OHRQoL. [ABSTRACT FROM AUTHOR]

BackgroundHIV-infected individuals have a higher incidence of head and neck cancer (HNC).MethodsCase series of 94 HIV-infected HNC patients (HIV-HNC) at 6 tertiary care referral centers in the US between 1991 and 2011. Clinical and risk factor data were abstracted from the medical record. Risk factors for survival were analyzed using Cox proportional hazard models. Human papillomavirus (HPV) and p16 testing was performed in 46 tumors. Findings were compared with Surveillance Epidemiology and End Results HNC (US-HNC) data.ResultsThis study represents the largest HIV-HNC series reported to date. HIV-HNC cases were more likely than US-HNC to be male (91% vs. 68%), younger (median age, 50 vs. 62 years), nonwhite (49% vs. 18%), and current smokers (61% vs. 18%). Median HIV-HNC survival was not appreciably lower than US-HNC survival (63 vs. 61 months). At diagnosis, most cases were currently on highly active antiretroviral therapy (77%) but had detectable HIV viremia (99%), and median CD4 was 300 cells per microliter (interquartile range = 167-500). HPV was detected in 30% of HIV-HNC and 64% of HIV-oropharyngeal cases. Median survival was significantly lower among those with CD4 counts ≤200 than >200 cells per microliter at diagnosis (16.1 vs. 72.8 months, P < 0.001). In multivariate analysis, poorer survival was associated with CD4

Abstract The prevalence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally while the prevalence of other head and neck cancers is decreasing. The most likely reasons for this are a decreasing influence of smoking and the growing relevance of infections with the human papilloma virus (HPV) as a risk factor. A rise in the HPV‐attributable fraction (HPV‐AF) of OPSCC has been observed in many countries, yet a comprehensive review of prevalence rates and trends in Germany is lacking. To determine the current HPV‐AF of OPSCC in Germany and to assess whether it has changed during the last decades, we performed a systematic literature review. We screened Medline and EMBASE for studies that reported the tumor HPV status of newly diagnosed OPSCC patients treated at medical centers in Germany by testing for both HPV DNA and p16INK4a overexpression to confirm involvement of HPV in tumorigenesis. Out of 287 screened studies, 14 studies with data from a total of 1819 OPSCC patients treated between 1988 and 2015 were included in the data synthesis. The reported average HPV‐AF varied considerably between the studies, ranging from 11.5% (1988‐2008) to 55.0% (2004‐2009). Two of the included studies did not only provide the HPV‐AF for the entire observed calendar period but also for separate years, allowing to more accurately assess changes over time. These studies reported increases in the HPV‐AF from 21% in 2000 to 53% in 2015 and from 38% in 2004 to 71% in 2013, respectively.

Purpose: This study aimed to evaluate the associations between immune-related gene (FCRL3, NLRP3 and IL2) polymorphisms and the risk of head and neck cancer (HNC). Methods: Six polymorphisms of FCRL3, NLRP3 and IL2 were genotyped in 400 HNC cases and 400 controls using a MassARRAY platform. Results: rs11264799-T was a protective variant against HNC risk, while rs7528684-G, rs35829419-A and rs6822844-T were all risk alleles for HNC (p < 0.05). rs11264799-TT was correlated with reduced HNC risk, while rs7528684-GG and rs6822844-TG were associated with an elevated risk of disease (p < 0.05). Moreover, rs11264799 was correlated with a declining risk of HNC in three genetic models (p < 0.05). In contrast, rs7528684 exhibited an elevated risk of HNC in recessive and additive models; rs35829419 and rs6822844 were associated with an increased risk of disease in dominant and additive models (p < 0.05). Finally, an interaction was observed between the above SNPs and drinking (p < 0.05). Conclusion: The results expand our knowledge on immune-related gene polymorphisms in HNC and provide clues for further functional study on the pathogenesis of HNC. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer (HNC) is one of the more common malignant tumors that threaten human health worldwide. Multidisciplinary team management (MDTM) in HNC treatment has been introduced in the past several decades to improve patient survival rates. This study reviewed the impact of MDTM on survival rates in patients with HNC compared to conventional treatment methods.Methods: Only cohort studies were identified for this meta-analysis that included an exposure group that utilized MDTM and a control group. Heterogeneity and sensitivity also were assessed. Survival rate data for HNC patients were analyzed using RevMan 5.2 software.Results: Five cohort studies (n = 39,070) that examined survival rates among HNC patients were included. Hazard ratios (HR) were calculated using the random effect model. The results revealed that exposure groups treated using MDTM exhibited a higher survival rate [HR = 0.84, 95% CI (0.76–0.92), P = 0.0004] with moderate heterogeneity (I2 = 68%, p = 0.01). For two studies that examined the effect of MDTM on the survival rate for patients specifically with stage IV HNC, MDTM did not produce any statistically significant improvement in survival rates [HR = 0.81, 95% CI (0.59–1.10), p = 0.18].Conclusions: The application of MDTM based on conventional surgery, radiotherapy, and chemotherapy improved the overall survival rate of patients with HNC. Future research should examine the efficacy of MDTM in patients with cancer at different stages.

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer (HNC) is one of the more common malignant tumors that threaten human health worldwide. Multidisciplinary team management (MDTM) in HNC treatment has been introduced in the past several decades to improve patient survival rates. This study reviewed the impact of MDTM on survival rates in patients with HNC compared to conventional treatment methods. Methods: Only cohort studies were identified for this meta-analysis that included an exposure group that utilized MDTM and a control group. Heterogeneity and sensitivity also were assessed. Survival rate data for HNC patients were analyzed using RevMan 5.2 software. Results: Five cohort studies (n = 39,070) that examined survival rates among HNC patients were included. Hazard ratios (HR) were calculated using the random effect model. The results revealed that exposure groups treated using MDTM exhibited a higher survival rate [HR = 0.84, 95% CI (0.76–0.92), P = 0.0004] with moderate heterogeneity (I 2 = 68%, p = 0.01). For two studies that examined the effect of MDTM on the survival rate for patients specifically with stage IV HNC, MDTM did not produce any statistically significant improvement in survival rates [HR = 0.81, 95% CI (0.59–1.10), p = 0.18]. Conclusions: The application of MDTM based on conventional surgery, radiotherapy, and chemotherapy improved the overall survival rate of patients with HNC. Future research should examine the efficacy of MDTM in patients with cancer at different stages. [ABSTRACT FROM AUTHOR]

Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO‐HNC (Heidelberg Center for Personalized Oncology‐head and neck cancer) (n = 83) and TCGA‐HNSC (The Cancer Genome Atlas‐Head and Neck Squamous Cell Carcinoma) (n = 506) cohorts revealed five common mutational signatures (Catalogue of Somatic Mutations in Cancer [COSMIC] Signatures 1, 2, 3, 13 and 16) and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16). Unsupervised hierarchical clustering identified four clusters (A, B, C1 and C2) of which Subcluster C2 was enriched for cases with a higher frequency of signature 16 mutations. Tumors of Subcluster C2 had significantly lower p16INK4A expression accompanied by homozygous CDKN2A deletion in almost one half of cases. Survival analysis revealed an unfavorable prognosis for patients with tumors characterized by a higher mutation burden attributed to signature 16 as well as cases in Subcluster C2. Finally, a LASSO‐Cox regression model was applied to prioritize clinically relevant signatures and to establish a prognostic risk score for head and neck squamous cell carcinoma patients. In conclusion, our study provides a proof of concept that computational analysis of somatic mutational signatures is not only a powerful tool to decipher environmental and intrinsic processes in the pathogenesis of HNC, but could also pave the way to establish reliable prognostic patterns. What's new? Progression of head and neck squamous cell carcinoma (HNSCC) is associated with the accumulation of multiple genetic and epigenetic alterations. Elucidating these mutational processes and their connections to tumor etiology and progression could have significant implications for HNSCC diagnosis and treatment. Here, using various computational analyses, the authors identified five mutational signatures in the COSMIC database associated specifically with HNSCC etiological risk factors and clinical outcome. Tumors with a high frequency of COSMIC signature 16 mutations had reduced p16INK4A expression with homozygous CDKN2A deletion, which may represent a critical step in the pathogenesis of a distinct HNSCC subgroup. [ABSTRACT FROM AUTHOR]

Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPVrelated cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To characterise the role of VEGF, EG‐VEGF and its receptors in the development and progression of HNC. Design: Human serum and tissues samples were collected from healthy, epulis and HNC patients and used for ELISA assays and immunohistochemistry studies, respectively. Setting: Ibn Rochd Hospital of Casablanca (Morocco), INSERM and University of Grenoble Alpes (France). Participants: We used serum from 64 patients with head and neck cancers and from 71 controls without general pathology. Tissues samples were collected from seven patients with OSCC and from seven patients with Epulis. Main outcome measures: We compared circulating VEGF and EG‐VEGF in normal and HNC patients and determined the expression, localisation and quantification of VEGF, EG‐VEGF and its receptors; PROKR1 and PROKR2 as well as Ki67, CD31 and CD34 in OSCC and Epulis patients. Results: Both EG‐VEGF and VEGF circulating levels were significantly decreased in the HNC (P <.01). OSCC patients expressed less EG‐VEGF and VEGF proteins, higher PROKR1 and PROKR2 with no change in CD31 and CD34 levels. A significant increase in Ki67 was observed in OSCC. Conclusions: We demonstrated that circulating VEGF and EG‐VEGF are downregulated in HNC patients and in OSCC tissue. EG‐VEGF receptors were increased in OSCC, along with a stabilisation of two key markers of angiogenesis. These findings strongly suggest that downregulation of angiogenesis in HNC might explain its moderate metastatic feature. [ABSTRACT FROM AUTHOR]

In this work, the performance of transition metal-doped gallium nitride nanosheets (M- GaNNS s, M = Cr, Fe, Ni and Zn) for adsorption and sensing of HCN, HNC and CH 3 CN toxic gases were investigated at the Grimme-corrected Perdew–Burke-Ernzerhof/double numerical plus polarization (PBE/DNP) level of theory. The electronic properties, structural parameters, adsorption energies, density of states (DOS) curves, band gap energies and charge transfer values were analyzed to find the ability of eight metal-doped GaNNS in adsorbing and sensing HCN, HNC and CH 3 CN gases. Compared with pure GaNNS , in all eight metal-doped configurations, the adsorption energies were increased after the doping of metals, especially their value in 2-HCN-Fe N GaNNS , 2-HNC-Fe N GaNNS and 2-CH 3 CN-Fe N GaNNS were greater than in others. Therefore, the Fe N GaNNS may be a suitable candidate for adsorbing and removing all the three studied gases from the atmosphere. Upon adsorption of HCN, HNC and CH 3 CN gases on the metal-doped GaNNS , a significant change in the energy gap is found in 2-HCN-Cr N GaNNS , 1-HNC-Fe Ga GaNNS and 2-CH 3 CN-Cr N GaNNS complexes, and, in turn, in the conductivity of nanostructures. Therefore, it is predicted that, Cr N GaNNS for sensing HCN and CH 3 CN gases and Fe Ga GaNNS for sensing HNC gas have a high potential. Although, Fe Ga GaNNS could be a good sensor for HCN and CH 3 CN gases in the second step and after Cr N GaNNS. [Display omitted] [ABSTRACT FROM AUTHOR]

Cristiana Lo Nigro,1 Nerina Denaro,1 Anna Merlotti,2 Marco Merlano1 1Department of Oncology, 2Department of Radiation Oncology, S. Croce and Carle Teaching Hospital, Cuneo, Italy Abstract: For early-stage head and neck cancer (HNC), surgery (S) or radiotherapy (RT) is a standard treatment. The multidisciplinary approach, which includes multimodality treatment with S followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy (CRT), is required for locally advanced head and neck cancer (LAHNC). CRT improves prognosis, locoregional control (LRC), and organ function in LAHNC, compared to RT alone. Prognosis in recurrent/metastatic HNC (R/M HNC) is dismal. Platinum-based CT, combined with the anti-Epidermal Growth Factor Receptor (EGFR) antibody (Ab) cetuximab, is used in first-line setting, while no further validated options are available at progression. The complexity of disease is, in part, due to the heterogeneity of organs and functions involved and the need for a multimodality approach. In addition, the patient population (often elderly and/or patients with smoking and alcohol habits) argues for an individually tailored treatment plan. Furthermore, treatment goals – which include cure, organ, and function preservation, quality of life and palliation – must also be considered. Thus, optimal management of patients with HNC should involve a range of healthcare professionals with relevant expertise. The purpose of the present review is to 1) highlight the importance and necessity of the multidisciplinary approach in the treatment of HNC; 2) update the knowledge regarding modern surgical techniques, new medical and RT treatment approaches, and their combination; 3) identify the treatment scenario for LAHNC and R/M HNC; and 4) discuss the current role of immunotherapy in HNC. Keywords: HNC, multimodality treatment, multidisciplinary team

Abstract Background In patients with head-neck cancer treated with IMRT, immobility of the upper part of the body during radiation is maintained by means of customised immobilisation devices. The main purpose of this study was to determine how the procedures for preparation of customised immobilisation systems and the patients characteristics influence the extent of setup errors. Methods A longitudinal, prospective study involving 29 patients treated with IMRT. Data were collected before CT simulation and during all the treatment sessions (528 setup errors analysed overall); the correlation with possible risk factors for setup errors was explored using a linear mixed model. Results Setup errors were not influenced by the patient’s anxiety and pain. Temporary removal of the thermoplastic mask before carrying out the CT simulation shows statistically borderline, clinically relevant, increase of setup errors (+24.7%, 95% CI: −0.5% - 55.8%). Moreover, a unit increase of radiation therapists who model the customised thermoplastic mask is associated to a −18% (−29.2% - -4.9%) reduction of the errors. The setup error is influenced by the patient’s physical features; in particular, it increases both in patients in whom the treatment position is obtained with ‘Shoulder down’ (+27.9%, 2.2% - 59.7%) and in patients with ‘Scoliosis/kyphosis’ problems (+65.4%, 2.3% - 164.2%). Using a ‘Small size standard plus customized neck support device’ is associated to a −52.3% (−73.7% - -11.2%) reduction. The increase in number of radiation therapists encountered during the entire treatment cycle does not show associations. Increase in the body mass index is associated with a slight reduction in setup error by (−2.8%, −5% - -0.7%). Conclusion The position of the patient obtained by forcing the shoulders downwards, clinically significant scoliosis or kyphosis and the reduction of the number of radiation therapists who model the thermoplastic mask are found to be statistically significant risk factors that can cause an increase in setup errors, while the use of ‘Small size’ neck support device and patient BMI can diminish them.