Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients.

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.

[Box: see text].

Efficacy of chemoradiotherapy in elderly patients with stage IV inoperable head and neck cancer.

OBJECTIVES: This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC). METHODS: Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). RESULTS: A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older. CONCLUSIONS: This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment.

A convolutional neural network with self-attention for fully automated metabolic tumor volume delineation of head and neck cancer in [Formula: see text]F]FDG PET/CT.

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 [Formula: see text]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 [Formula: see text]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) ([Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] in cross-validation and [Formula: see text]; [Formula: see text] vs. [Formula: see text]; [Formula: see text] 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.

Speech and Swallowing Rehabilitation Potentially Decreases Body Weight Loss and Improves Survival in Head and Neck Cancer Survivors.

This retrospective observational cohort study aims to assess the outcomes and associated factors in head and neck cancer (HNC) survivors with dysphagia, and to investigate the relationship between outcomes and speech and swallowing rehabilitation (SSR). We enrolled patients who were diagnosed with HNC between October 2016 and July 2018; we included 393 patients who developed dysphagia after definite treatment and were referred to speech-language pathologists (SLPs). We then classified patients into groups according to whether they received SSR. We used the clinical variables-including age, sex, site of malignancy, cancer stage, treatment modality, SSR, initial ECOG score, initial KPS, initial body weight (BW), and initial BMI-to evaluate the association between the percentage of BW change and overall survival (OS). There were 152 (39%) and 241 (61%) patients who received and did not receive SSR, respectively. In multivariate linear regression, SSR was significantly associated with percentage change in BW at 3 months post-treatment. Having SSR was positively associated with the percentage change in BW and decreased the BW loss [ß coefficient (95% CIs) = 2.53 (0.92 to 4.14)] compared to having no SSR. In the multivariate Cox regression, SSR was an independent factor for OS. Compared to no SSR, the hazard ratio (95% CIs) for patients who received SSR was 0.48 (0.31 to 0.74). SSR helps to avoid BW loss and increases overall survival. HNC patients who develop dysphagia after treatment should be encouraged to participate in SSR.

Head and Neck Cancer Patients' Survival According to HPV Status, miRNA Profiling, and Tumour Features-A Cohort Study.

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.

Matrix Metalloproteinases and Their Inhibitors as Potential Prognostic Biomarkers in Head and Neck Cancer after Radiotherapy.

Head and neck cancer (HNC) is among the ten most frequent tumours, with 5-year survival rates varying from 30% to 70% depending on the stage and location of the tumour. HNC is traditionally known as head and neck squamous cell carcinoma (HNSCC), since 90% arises from epithelial cells. Metastasis remains a major cause of mortality in patients with HNSCC. HNSCC patients with metastatic disease have an extremely poor prognosis with a survival rate of less than a year. Matrix metalloproteinases (MMPs) have been described as biomarkers that promote cell migration and invasion. Radiotherapy is widely used to treat HNSCC, being a determining factor in the alteration of the tumour's biology and microenvironment. This review focuses on analysing the current state of the scientific literature on this topic. Although few studies have focused on the role of these proteinases in HNC, some authors have concluded that radiotherapy alters the behaviour of MMPs and tissue inhibitors of metalloproteinases (TIMPs). Therefore, more research is needed to understand the roles played by MMPs and their inhibitors (TIMPs) as prognostic biomarkers in patients with HNC and their involvement in the response to radiotherapy.

DNA Damage Response Mechanisms in Head and Neck Cancer: Significant Implications for Therapy and Survival.

Head and neck cancer (HNC) is a term collectively used to describe a heterogeneous group of tumors that arise in the oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx, and represents the sixth most common type of malignancy worldwide. Despite advances in multimodality treatment, the disease has a recurrence rate of around 50%, and the prognosis of metastatic patients remains poor. HNCs are characterized by a high degree of genomic instability, which involves a vicious circle of accumulating DNA damage, defective DNA damage repair (DDR), and replication stress. Nonetheless, the damage that is induced on tumor cells by chemo and radiotherapy relies on defective DDR processes for a successful response to treatment, and may play an important role in the development of novel and more effective therapies. This review summarizes the current knowledge on the genes and proteins that appear to be deregulated in DDR pathways, their implication in HNC pathogenesis, and the rationale behind targeting these genes and pathways for the development of new therapies. We give particular emphasis on the therapeutic targets that have shown promising results at the pre-clinical stage and on those that have so far been associated with a therapeutic advantage in the clinical setting.

Dose difference between anisotropic analytical algorithm (AAA) and Acuros XB (AXB) caused by target's air content for volumetric modulated arc therapy of head and neck cancer.

Background: We clarified the dose difference between the anisotropic analytical algorithm (AAA) and Acuros XB (AXB) with increasing target's air content using a virtual phantom and clinical cases. Materials and methods: Whole neck volumetric modulated arc therapy (VMAT) plan was transferred into a virtual phantom with a cylindrical air structure at the center. The diameter of the air structure was changed from 0 to 6 cm, and the target's air content defined as the air/planning target volume (PTV) in percent (air/PTV) was varied. VMAT plans were recalculated by AAA and AXB with the same monitor unit (MU) and multi-leaf collimator (MLC) motions. The dose at each air/PTV (5%-30%) was compared between each algorithm with D98%, D95%, D50% and D2% for the PTV. In addition, MUs were also compared with the same MLC motions between the D95% prescription with AAA (AAA_D95%), AXB_D95%, and the prescription to 100% minus air/PTV (AXB_D100%-air/PTV) in clinical cases of head and neck (HNC). Results: When air/PTV increased (5-30%), the dose differences between AAA and AXB for D98%, D95%, D50% and D2% were 3.08-15.72%, 2.35-13.92%, 0.63-4.59%, and 0.14-6.44%, respectively. At clinical cases with air/PTV of 5.61% and 28.19%, compared to AAA_D95%, the MUs differences were, respectively, 2.03% and 6.74% for AXB_D95% and 1.80% and 0.50% for AXB_D100%-air/PTV. Conclusion: The dose difference between AAA and AXB increased as the target's air content increased, and AXB_D95% resulted in a dose escalation over AAA_D95% when the target's air content was ≥ 5%. The D100%-air/PTV of PTV using AXB was comparable to the D95% of PTV using AAA.

Role of genetic variations of DNA damage response pathway genes and heat-shock proteins in increased head and neck cancer risk.

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.

Impact of HPV status on metastatic patterns and survival in non-oropharyngeal head and neck cancer with distant metastasis.

PURPOSE: Because of the lack of data and studies on metastatic non-oropharyngeal head and neck cancer (non-OP HNC), the role of human papillomavirus (HPV) status in non-OP HNC with distant metastasis is still unclear. Therefore, we conducted a study to explore the differences in metastatic patterns, survival and treatment responses in metastatic non-OP HNC based on HPV status. METHODS: A total of 333 metastatic non-OP HNC patients were diagnosed from 2010 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database. The chi-square test and Fisher's exact test were used to make comparisons for categorical variables. The Kaplan-Meier method and Cox regression analyses were used to analyse survival. RESULTS: HPV status was a significant prognostic variable for patients with non-OP HNC with distant metastasis. HPV- patients were more likely to have distant metastasis and worse prognosis and treatment response than HPV+ patients. Only chemotherapy was an independent prognostic factor for HPV+ patients with distant metastasis, while chemotherapy and radiotherapy were both independent prognostic factors for HPV- patients with distant metastasis. The treatment response was associated with the metastatic pattern in both HPV+ and HPV- populations and showed significant differences based on HPV status and metastatic pattern. CONCLUSIONS: For non-OP HNC with distant metastasis, HPV+ and HPV- patients formed two different cohorts in terms of metastatic pattern, survival and treatment. Therefore, it is helpful to classify metastatic non-OP HNC into different groups to choose appropriate treatment strategies according to HPV status and metastatic pattern.

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs.

Head and neck cancers (HNCs) comprise a heterogeneous group of tumors that extend from the oral cavity to the upper gastrointestinal tract. The principal etiologic factors for oral tumors include tobacco smoking and alcohol consumption, while human papillomavirus (HPV) infections have been accused of a high incidence of pharyngeal tumors. Accordingly, HPV detection has been extensively used to categorize carcinomas of the head and neck. The diverse nature of HNC highlights the necessity for novel, sensitive, and precise biomarkers for the prompt diagnosis of the disease, its successful monitoring, and the timely prognosis of patient clinical outcomes. In this context, the identification of certain microRNAs (miRNAs) and/or the detection of alterations in their expression patterns, in a variety of somatic fluids and tissues, could serve as valuable biomarkers for precision oncology. In the present review, we summarize some of the most frequently studied miRNAs (including miR-21, -375, -99, -34a, -200, -31, -125a/b, -196a/b, -9, -181a, -155, -146a, -23a, -16, -29, and let-7), their role as biomarkers, and their implication in HNC pathogenesis. Moreover, we designate the potential of given miRNAs and miRNA signatures as novel diagnostic and prognostic tools for successful patient stratification. Finally, we discuss the currently ongoing clinical trials that aim to identify the diagnostic, prognostic, or therapeutic utility of miRNAs in HNC.

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence of 650,000 new cases and 350,000 deaths per year worldwide and a male to female ratio of 3:1. The main risk factors are alcohol and tobacco consumption and Human Papillomavirus (HPV) infections. HNSCC cases are divided into two subgroups, the HPV-negative (HPV-) and the HPV-positive (HPV+) which have different clinicopathological and molecular profiles. However, patients are still treated with the same therapeutic regimens. It is thus of utmost importance to characterize the molecular mechanisms underlying these differences to find new biomarkers and novel therapeutic targets towards personalized therapies. Epigenetic alterations are a hallmark of cancer and can be exploited as both promising biomarkers and potential new targets. E6 and E7 HPV oncoviral proteins besides targeting p53 and pRb, impair the expression and the activity of several epigenetic regulators. While alterations in DNA methylation patterns have been well described in HPV+ and HPV- HNSCC, accurate histone post-translational modifications (hPTMs) characterization is still missing. Herein, we aim to provide an updated overview on the impact of HPV on the hPTMs landscape in HNSCC. Moreover, we will also discuss the sex and gender bias in HNSCC and how the epigenetic machinery could be involved in this process, and the importance of taking into account sex and/or gender also in this field.

Unraveling most abundant mutational signatures in head and neck cancer.

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.

Depression, anxiety, fatigue, and quality of life in a large sample of patients suffering from head and neck cancer in comparison with the general population.

BACKGROUND: Treatment of head and neck cancer (HNC) often leads to visible and severe functional impairments. In addition, patients often suffer from a variety of psychosocial problems, significantly associated with a decreased quality of life. We aimed to compare depression, anxiety, fatigue and quality of life (QoL) between HNC patients and a large sample of the general population in Germany and to examine the impact of sociodemographic, behavioral and clinical factors on these symptoms. METHODS: We assessed data of HNC patients during the aftercare consultation at the Leipzig University Medical Center with a patient reported outcome (PRO) tool named "OncoFunction". Depression, anxiety, fatigue and QoL were assessed using validated outcome measures including the PHQ-9, the GAD-2, and the EORTC QLQ-C30 questionnaire. RESULTS: A total of 817 HNC patients were included in our study and compared to a sample of 5018 individuals of the general German population. HNC patients showed significantly higher levels of impairment in all dimensions assessed. Examination of association between depression, anxiety, fatigue and QoL and clinical as well as sociodemographic variables showed significant relationships between occupational status, ECOG-state, body mass index and time since diagnosis. CONCLUSIONS: HNC patients suffer significantly from psychological distress. The used questionnaires are suitable for the use in daily routine practice and can be helpful to increase the detection of depression, anxiety and fatigue and therefore can improve HNC aftercare.

Rising incidence of late-stage head and neck cancer in the United States.

BACKGROUND: The current study was conducted to determine whether the incidence of late-stage head and neck cancer (HNC) is decreasing and to estimate the risk of late-stage HNC diagnosis based on race and sex. METHODS: Age-adjusted incidence rates for patients aged ≥18 years with stage IV HNC were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2015). Rates were stratified by race, sex, and age. Joinpoint regression estimated annual percent changes (APCs) in rates over time, and logistic regression estimated adjusted odds ratios (aORs). RESULTS: There were 57,118 patients with stage IV HNC in the current study cohort, with an average age of 61.9 years. From 2004 to 2015, the age-adjusted incidence rates for stage IV HNC significantly increased by 26.1% (6.11 per 100,000 person-years in 2004 to 7.70 per 100,000 person-years in 2015). White and Asian/Pacific Islander/American Indian/Alaska Native patients had significant increases in incidence (APC for white patients, 3.03 [P < .01] and APC for other races, 1.95 [P < .01]), whereas rates among black patients remained stable but were highest across racial groups. Incidence was higher among males compared with females. When restricted only to patients with stage IVC (metastatic) HNC, there remained a significant increase in incidence, especially for oropharyngeal cancer, which showed a 22.9% increase (0.21 per 100,000 person-years in 2004 vs 0.25 per 100,000 person-years in 2015). Despite a decreasing overall incidence of stage IV HNC in black patients (aOR, 1.28; 95% CI, 1.22-1.34) they, along with males (aOR, 3.95; 95% CI, 3.80-4.11), had significantly increased risks of being diagnosed with late-stage HNC. CONCLUSIONS: There is an increasing incidence of late-stage HNC in the United States, with male patients and black individuals faring the worst.

Reliability and validity of the mandarin version of the supportive care needs survey short-form (SCNS-SF34) and the head and neck cancer-specific supportive care needs (SCNS-HNC) module.

BACKGROUND: This study aimed to translate the English version of the supportive care needs scale of head and neck cancer patients (SCNS-HNC) questionnaire into Mandarin and to test the reliability and validity of the SCNS-SF34 and SCNS-HNC module in head and neck cancer patients. METHODS: The Mandarin version of the Supportive Care Needs Survey Short-Form (SCNS-SF34) and SCNS-HNC scales were used to assess 206 patients with head and neck cancer in Chengdu, China. Among them, 51 patients were re-tested 2 or 3 days after the first survey. The internal consistency of the scale was evaluated by Cronbach's alpha coefficient, the retest reliability of the scale was evaluated by retest correlation coefficient r, the structural validity of the scale was evaluated by exploratory factor analysis, and the ceiling and floor effects of the scale were evaluated. RESULTS: The Mandarin version of the SCNS-HNC had Cronbach's alpha coefficients greater than 0.700 (0.737 ≤ 0.962) for all of the domains. Except for the psychological demand dimension (r = 0.674) of the SCNS-SF34 scale, the retest reliability of the other domains was greater than 0.8. Three common factors were extracted by exploratory factor analysis, and the cumulative variance contribution rate was 64.39%. CONCLUSIONS: The Mandarin version of the SCNS-SF34 and SCNS-HNC demonstrated satisfactory reliability and validity and is able to measure the supportive care needs of Chinese patients with head and neck cancer. TRIAL REGISTRATION: ChiCTR, ChiCTR1900026635 . Registered 16 October 2019- Retrospectively registered.

Vascular endothelial growth factor (VEGF) and Endocrine gland-VEGF (EG-VEGF) are down regulated in head and neck cancer.

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.

Impact of oat processing on glycaemic and insulinaemic responses in healthy humans: a randomised clinical trial.

Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey's test (two-sided P<0·05) to compare individual means. Glucose peak-rise (primary endpoint, mean (sem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.

Relationship of single nucleotide polymorphisms and haplotype interaction of mitochondrial unfolded protein response pathway genes with head and neck cancer.

Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPRmt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials & methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPRmt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPRmt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.