A translation and validation of the French version of the Gothenburg Trismus Questionnaire 2 (F-GTQ-2).

BACKGROUND: Limitation of mouth opening, widely known as trismus, is a major symptom altering quality of life in individuals presenting from temporomandibular joint disorder or head and neck cancer. A French-language instrument addressing jaw opening limitation following treatment for head and neck cancer (HNC) or temporomandibular joint disorder (TMD) is lacking. OBJECTIVE: The aim of this study was to translate and validate the Gothenburg Trismus Questionnaire-2 (GTQ-2) into French. METHODS: A French translation of the GTQ-2 was performed according to established international guidelines, leading to the French-GTQ-2 (F-GTQ-2). The validation study included 154 participants with trismus (minimum interincisal opening of ≤35 mm) following treatment for TMD or HNC and 149 age-matched participants without trismus. All participants completed the F-GTQ-2 and participants with trismus completed additional health-related quality of life questionnaires to allow for analysis of convergent validity. RESULTS: The F-GTQ-2 demonstrated retained psychometric properties with Cronbach's alpha values above 0.70 for the domains, jaw-related problems, eating limitations, facial pain and somewhat lower for muscular tension (0.60). Mainly moderate correlations were found when comparing the F-GTQ-2 to other instruments, which was in line with the pre-specified hypotheses, indicating satisfactory convergent validity. Discriminant validity was found with statistically significant differences in all domains of the F-GTQ-2 between trismus and non-trismus participants. CONCLUSION: The F-GTQ-2 can be considered a reliable and valid instrument to assess jaw-related difficulties in individuals with trismus due to HNC or TMD.

m7G-related genes-NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression.

Aberrant N7 -methylguanosine (m7G) levels closely correlate with tumor genesis and progression. NCBP2 and EIF4E3 are two important m7G-related cap-binding genes. This study aimed to identify the relationship between the EIF4E3/NCBP2 function and immunological characteristics of head and neck squamous cell carcinoma (HNSCC). Hierarchical clustering was employed in classifying HNSCC patients into two groups based on the expressions of NCBP2 and EIF4E3. The differentially expressed genes were identified between the two groups, and GO functional enrichment was subsequently performed. Weighted gene co-expression network analysis was conducted to identify the hub genes related to EIF4E3/NCBP2 expression and immunity. The differential infiltration of immune cells and the response to immunotherapy were compared between the two groups. Single-cell sequence and trajectory analyses were performed to predict cell differentiation and display the expression of EIF4E3/NCBP2 in each state. In addition, quantitative real-time PCR, spatial transcriptome analysis, transwell assay, and western blotting were conducted to verify the biological function of EIF4E3/NCBP2. Here, group A showed a higher EIF4E3 expression and a lower NCBP2 expression, which had higher immune scores, proportion of most immune cells, immune activities, expression of immunomodulatory targets, and a better response to cancer immunotherapy. Besides, 56 hub molecules with notable immune regulation significance were identified. A risk model containing 17 hub genes and a prognostic nomogram was successfully established. Moreover, HNSCC tissues had a lower EIF4E3 expression and a higher NCBP2 expression than normal tissues. NCBP2 and EIF4E3 played a vital role in the differentiation of monocytes. Furthermore, the expression of CCL4/CCL5 can be regulated via EIF4E3 overexpression and NCBP2 knockdown. Collectively, NCBP2 and EIF4E3 can affect downstream gene expression, as well as immune contexture and response to immunotherapy, which could induce "cold-to-hot" tumor transformation in HNSCC patients.

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications.

Oral squamous cell carcinoma (OSCC) is particularly prevalent in Taiwan. The goal of this study was to determine the clinicopathological role of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) proteins as an indicator of clinical outcomes in OSCC patients. In this study, immunohistochemical (IHC) analysis was used to examine IGF2BP2 protein expression in 244 OSCC patients. We investigated the relationships among IGF2BP2 expression, clinicopathological variables, and patient survival. Our results showed that IGF2BP2 cytoplasmic protein expression was significantly correlated with lymph node metastasis, cancer stage, and patient survival. Kaplan-Meier survival curves revealed that elevated cytoplasmic IGF2BP2 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate cox proportional hazard models revealed that cytoplasmic IGF2BP2 expression, T status, and lymph node metastasis were independent prognostic factors for survival. In conclusion, IGF2BP2 protein was found to be a helpful predictive marker for OSCC patients, as well as a possible therapeutic target for OSCC treatment.

Feasibility and Efficacy of Inspiratory Muscle Training in Patients with Head and Neck Cancer receiving Concurrent Chemoradiotherapy.

OBJECTIVES: Patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT) often experience pulmonary symptoms. This study evaluated if a 7-week inspiratory muscle training (IMT) program during CCRT is feasible, adherent, and safe in patients with HNC. This study also evaluated the effect of IMT on diaphragm thickness, mobility, and cardiorespiratory parameters in patients with HNC receiving CCRT. METHODS: Ten participants with advanced stage HNC receiving CCRT were recruited for the study. Feasibility, adherence, and safety of the intervention were the primary outcomes. Changes in diaphragm thickness and mobility, maximal inspiratory pressure, maximal expiratory pressure, forced vital capacity, forced expiratory volume in first second and functional capacity using 6-MWT were measured at baseline and post 7 weeks of CCRT. IMT was performed at one session per day for 5 days a week for 7 weeks. Eight sets of two minutes of inspiratory manoeuvres with one minute rest period between them with intensity of 40% MIP were given. RESULTS: Ten participants  were included in this study out of the 13 patients screened, indicating the feasibility to be 76.9%. Participants completed a total of 260 training sessions out of the 350 planned sessions denoting the adherence level as 74%. Diaphragm thickness and MEP remained significantly unchanged while significant decline was seen in diaphragm mobility, MIP,FVC, FEV1 and 6-MWD at the end of 7 weeks. No adverse events were reported following the intervention. CONCLUSION: Inspiratory muscle training did not show significant effect on the diaphragm thickness, mobility, and cardiorespiratory parameters; however, it was feasible, adherent, and safe in patients with HNC receiving CCRT.

Fibroblast growth factor (FGF), FGF receptor (FGFR), and cyclin D1 (CCND1) DNA methylation in head and neck squamous cell carcinomas is associated with transcriptional activity, gene amplification, human papillomavirus (HPV) status, and sensitivity to tyrosine kinase inhibitors.

BACKGROUND: Dysregulation of fibroblast growth factor receptor (FGFR) signaling pathway has been observed in head and neck squamous cell carcinoma (HNSCC) and is a promising therapeutic target for selective tyrosine kinase inhibitors (TKIs). Potential predictive biomarkers for response to FGFR-targeted therapies are urgently needed. Understanding the epigenetic regulation of FGF pathway related genes, i.e. FGFRs, FGFs, and CCND1, could enlighten the way towards biomarker-selected FGFR-targeted therapies. METHODS: We performed DNA methylation analysis of the encoding genes FGFR1, FGFR2, FGFR3, FGFR4, FGF1-14, FGF16-23, and CCND1 at single CpG site resolution (840 CpG sites) employing The Cancer Genome Research Atlas (TCGA) HNSCC cohort comprising N = 530 tumor tissue and N = 50 normal adjacent tissue samples. We correlated DNA methylation to mRNA expression with regard to human papilloma virus (HPV) and gene amplification status. Moreover, we investigated the correlation of methylation with sensitivity to the selective FGFR inhibitors PD 173074 and AZD4547 in N = 40 HPV(-) HNSCC cell lines. RESULTS: We found sequence-contextually nuanced CpG methylation patterns in concordance with epigenetically regulated genes. High methylation levels were predominantly found in the promoter flank and gene body region, while low methylation levels were present in the central promoter region for most of the analyzed CpG sites. FGFRs, FGFs, and CCND1 methylation differed significantly between tumor and normal adjacent tissue and was associated with HPV and gene amplification status. CCND1 promoter methylation correlated with CCND1 amplification. For most of the analyzed CpG sites, methylation levels correlated to mRNA expression in tumor tissue. Furthermore, we found significant correlations of DNA methylation of specific CpG sites with response to the FGFR1/3-selective inhibitors PD 173074 and AZD4547, predominantly within the transcription start site of CCND1. CONCLUSIONS: Our results suggest an epigenetic regulation of CCND1, FGFRs, and FGFs via DNA methylation in HNSCC and warrants further investigation of DNA methylation as a potential predictive biomarker for response to selective FGFR inhibitors in clinical trials.

Concurrent Chemoradiotherapy Induces Body Composition Changes in Locally Advanced Head and Neck Squamous Cell Carcinoma: Comparison between Oral Cavity and Non-Oral Cavity Cancer.

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC (n = 69) and NOCC (n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

Caveolin-1 and Sox-2 are predictive biomarkers of cetuximab response in head and neck cancer.

The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients for cetuximab therapy in HNSCC. Here, we applied unbiased hierarchical clustering to reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors and revealed 2 PDX clusters defined by protein networks associated with EGFR inhibitor resistance. In vivo validation revealed unbiased clustering to classify PDX tumors according to cetuximab response with 88% accuracy. Next, a support vector machine classifier algorithm identified a minimalist biomarker signature consisting of 8 proteins - caveolin-1, Sox-2, AXL, STING, Brd4, claudin-7, connexin-43, and fibronectin - with expression that strongly predicted cetuximab response in PDXs using either protein or mRNA. A combination of caveolin-1 and Sox-2 protein levels was sufficient to maintain high predictive accuracy, which we validated in tumor samples from patients with HNSCC with known clinical response to cetuximab. These results support further investigation into the combined use of caveolin-1 and Sox-2 as predictive biomarkers for cetuximab response in the clinic.

Change in Nutritional Status and Dysphagia after Resection of Head and Neck Cancer.

Nutritional status is well-known to influence patient recovery after resection of head and neck cancer (HNC). The influence of preoperative nutritional status on dysphagia was assessed in patients who underwent surgical resection of HNC along with the assessment of nutritional status during the acute and subacute phases. Eighty-six patients underwent surgical resection and dysphagia assessments (repetitive saliva-swallowing test, water-swallowing test, and functional oral intake scale) and had their tongue pressure assessed five times (before surgery, after 1-2 weeks, and 1, 2, and 3 months after surgery). The nutritional status was assessed according to the body mass index, total protein, and albumin. The prognostic nutritional index was calculated from preoperative data, and the subjects were classified into three groups: Low-risk, Attention and High-risk groups. After surgery, the nutritional status index values were low, and the High-risk group showed significantly lower values in comparison to the other two groups. The water-swallowing test and functional oral intake scale findings were worse than they had been preoperatively until 2 months after surgery, and a significant correlation was noted between the postoperative nutritional status and the presence of dysphagia. The results indicated that the preoperative nutritional status of HNC patients influenced their ability to ingest/swallow, which in turn influenced their nutritional status after HNC resection.

Chronic Nutrition Impact Symptoms Are Associated with Decreased Functional Status, Quality of Life, and Diet Quality in a Pilot Study of Long-Term Post-Radiation Head and Neck Cancer Survivors.

BACKGROUND: As a result of tumor location and treatment that is aggressive, head and neck cancer (HNC) survivors experience an array of symptoms impacting the ability and desire to eat termed nutrition impact symptoms (NISs). Despite increasing cancer survival time, the majority of research studies examining the impact of NISs have been based on clinical samples of HNC patients during the acute phase of treatment. NISs are often chronic and persist beyond the completion of treatment or may develop as late side effects. Therefore, our research team examined chronic NIS complications on HNC survivors' functional status, quality of life, and diet quality. METHODS: This was a cross-sectional study of 42 HNC survivors who were at least 6 months post-radiation. Self-reported data on demographics, NISs, quality of life, and usual diet over the past year were obtained. Objective measures of functional status included the short physical performance battery and InBody© 270 body composition testing. NISs were coded so a lower score indicated lower symptom burden, (range 4-17) and dichotomized as ≤10 vs. >10, the median in the dataset. Wilcoxon rank sum tests were performed between the dichotomized NIS summary score and continuous quality of life and functional status outcomes. Diet quality for HNC survivors was calculated using the Healthy Eating Index 2015 (HEI-2015). Wilcoxon rank sum tests examined the difference between the HNC HEI-2015 as compared to the National Health and Nutrition Examination Survey (NHANES) data calculated using the population ratio method. RESULTS: A lower NIS score was statistically associated with higher posttreatment lean muscle mass (p = 0.002). A lower NIS score was associated with higher functional (p = 0.0006), physical (p = 0.0007), emotional (p = 0.007), and total (p < 0.0001) quality of life. Compared to NHANES controls, HNC survivors reported a significantly lower HEI-2015 diet quality score (p = 0.0001). CONCLUSIONS: Lower NIS burden was associated with higher lean muscle mass and functional, physical, emotional, and total quality of life in post-radiation HNC survivors. HNC survivors reported a significantly lower total HEI-2015 as compared to healthy NHANES controls, providing support for the hypothesis that chronic NIS burden impacts the desire and ability to eat. The effects of this pilot study were strong enough to be detected by straight forward statistical approaches and warrant a larger longitudinal study. For survivors most impacted by NIS burden, multidisciplinary post-radiation exercise and nutrition-based interventions to manage NISs and improve functional status, quality of life, and diet quality in this survivor population are needed.

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies.

BACKGROUND: Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their 15N/14N. METHODS: Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. RESULTS: In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. CONCLUSIONS: The findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

Glia and Orofacial Pain: Progress and Future Directions.

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervous system, and microglia and astrocytes in the central nervous system, are important players in both peripheral and central processing of pain in the orofacial region. This review highlights recent molecular and cellular findings of the glia involvement and glia-neuron interactions in four common orofacial pain conditions such as headache, dental pulp injury, temporomandibular joint dysfunction/inflammation, and head and neck cancer. We will discuss the remaining questions and future directions on glial involvement in these four orofacial pain conditions.

Subjective and Objective Measures in Assessing Neck Disability and Pain in Head and Neck Cancer.

OBJECTIVE/HYPOTHESIS: The intensification of treatment for head and neck cancers (HNCs) has created a cohort of patients living with short- and long-term comorbidities and functional deficits. This study aimed to determine whether there is a relationship between patient-reported outcomes (PROs) and objective measures of neck function in survivors of HNCs. STUDY DESIGN: Cross-sectional study. METHODS: Thirty-one subjects (aged 64 ± 8.7 years; 28 males and three females) were recruited and completed the Neck Disability Index (NDI) and a numeric pain scale. At the same visit, subjects were fitted with two portable motion sensors to collect range of motion (ROM) and velocity data. Differences between ROM, velocity, and PRO subgroups were assessed using a one-tailed t test (*P < .05). The Pearson correlation coefficient (r) was calculated between the NDI values and the ROM and velocity values for each motion. RESULTS: A moderate correlation (r = 0.507) was observed between NDI and neck pain. Patients with no disability according to the NDI had significantly higher ROM and velocity than patients with mild to moderate disability. Velocity in all degrees of freedom (axial rotation, flexion and extension, and lateral bending) was significantly lower for patients who perceived higher levels of neck pain and neck disability. CONCLUSIONS: This study notes that patients who report neck disability and pain have more limited ROM and velocity following HNC treatment. These data may improve treatment planning and care delivery by facilitating an understanding of the experiences of HNC survivors and the pathophysiology that must be targeted to address their psychosocial and functional deficits. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2015-2022, 2021.

Different types of dysphagia alleviated by the chin-down position.

OBJECTIVE: Retrospective videofluoroscopic swallowing study (VFSS) evaluations of pharyngeal swallowing were used to evaluate the types of dysphagia alleviated by the chin-down maneuver. MATERIALS AND METHODS: The study population consisted of 64 patients who underwent VFSS evaluations during neutral and chin-down maneuvers presenting specifically penetration or aspiration. The assessment of the VFSS movie clips of each maneuver was performed using parameters of the Modified Barium Swallow Impairment Profile (MBSImP) and the presence and degree of airway invasion(PDAI) by three blinded raters in the following five subcategorized groups, 1. patietns presenting penetration or aspiration during swallow 2. after swallow, patients of 3. head and neck, 4. digestive and 5. neuromuscular disorders, respectively. The scores registered for the two maneuvers were statistically compared. Additionally, we examined statistically which factors had the impact on the improvement of the PDAI using fisher's exact test. RESULTS: Compared with the neutral position, PDAI, pharyngeal constriction, anterior hyoid movement, pharyngeal constriction, laryngeal elevation, laryngeal closure, upper esophageal sphincter opening, initiation of the pharyngeal swallow, and pharyngeal clearance in pyriform sinus were significantly (p < 0.01-0.05) improved with the chin-down maneuver. In a subcategory comparison with group 1, 3 and 4, the PDAI improved significantly (p < 0.01) with the chin-down maneuver, in which laryngeal elevation and laryngeal closure had statistically the impact (p < 0.01-0.05) on improvement of PDAI. CONCLUSION: The chin-down maneuver was most effective in improving swallow function when the impairment included penetration and aspiration during swallow caused by inadequate laryngeal elevation and laryngeal closure.

Social isolation stress facilitates chemically induced oral carcinogenesis.

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

Nutrition impact symptoms and weight loss in head and neck cancer during radiotherapy: a longitudinal study.

OBJECTIVE: Patients with head and neck cancer (HNC) receiving radiotherapy (RT) are at high risk of weight loss (WL) due to a variety of nutrition impact symptoms (NIS). This study aimed to describe the NIS through the Head and Neck patient Symptom Checklist and body weight over time and further explore the impact of NIS on WL in patients with HNC undergoing RT. METHODS: This was a prospective, longitudinal observational study. NIS and body weight of 117 participants were assessed at baseline, mid-treatment and post-treatment of RT. Generalised estimation equations (GEE) were used to conduct repeated measures analysis of NIS interference score and body weight at each time point and estimate the impact of NIS interference score on WL. RESULTS: All participants experienced a substantial increase in the mean number of NIS during RT, with each patient having eight to nine NIS at mid-treatment and post-treatment. Marked increases were noted in almost each NIS score during RT. Compared with their baseline body weight, 97 (82.9%) and 111 (94.9%) participants experienced WL at mid-treatment and post-treatment, with the mean WL of 2.55±1.70 kg and 5.31±3.18 kg, respectively. NIS of dry mouth (ß=-0.681, p=0.002, 95% CI -1.116 to -0.247), difficulty swallowing (ß=-0.410, p=0.001, 95% CI -0.651 to -0.169) and taste change (ß=-0.447, p=0.000, 95% CI -0.670 to -0.225) impacted WL significantly in GEE multivariate model. CONCLUSIONS: Patients with HNC experience a variety of NIS which have significant impact on WL during RT. Assessment of NIS, especially dry mouth, difficulty swallowing and taste change, should be given more considerable attention in the supportive care of patients with HNC.

Differential Wnt-ß- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications.

The aim of this study is to understand the association of HPV infection and wnt-ß-catenin self-renewal pathway in development of head and neck squamous cell carcinoma (HNSCC). For this reason, the molecular profiles (methylation/deletion/expression) of antagonists (SFRP1/2 and DKK1), agonists (FZD7 and LRP6) and effector protein ß-catenin of the pathway were analyzed in HPV positive/negative oral epithelium at first, followed by its changes during development of the tumor along with correlations with different clinico-pathological parameters. HPV infection alone or in combination with tobacco habit could activate p- ß-catenin expression in basal/parabasal layers of oral epithelium through high expression of FZD7 and significant down regulation of SFRP1/2 through promoter hypermethylation due to over expression of DNMT1 with ubiquitous down regulation of DKK1 and up-regulation of LRP6. This phenomenon has been seen in respective HPV positive and negative HNSCC tumors with additional deletion/microsatellite size alterations in the antagonists. Overall alterations (methylation/deletion) of SFRP1/2, DKK1 gradually increased from Group I (HPV-/Tobacco-) to Group IV(HPV+/Tobacco+) tumors, leading to the worst prognosis of the patients. Thus, the transmission of differentially activated wnt-ß-catenin pathway from HPV positive/negative basal/parabasal layers of oral epithelium to HNSCC tumors determines differences in molecular pathogenesis of the disease.

Cervical Fibrosis as a Predictor of Dysphagia.

OBJECTIVE: Radiotherapy of head and neck cancer (HNCA) causes dysfunction through radiation-induced fibrosis (RIF). We hypothesize that the degree of cervical fibrosis is associated with swallowing dysfunction. This study evaluated the association between cervical fibrosis and swallowing dysfunction in patients after radiation therapy for HNCA. STUDY DESIGN: Cross sectional study. METHODOLOGY: A convenience sample of patients with dysphagia who were at least 1 year post radiation therapy for HNCA underwent simultaneous cervical ultrasound (US) and video-fluroscopic swallow study (VFSS). US determinants of fibrosis were measurements of sternocleidomastoid fascia (SCMF) thickness bilaterally at the level of the cricoid. Primary and secondary outcome variables on VFSS were pharyngeal constriction ratio, a validated measure of pharyngeal contractility, and penetration aspiration scale (PAS). A qualitative assessment of lateral neck rotation was performed as a functional measure of neck fibrosis. RESULTS: Simultaneous cervical US and VFSS examinations were performed on 18 patients with a history of radiotherapy for HNCA and on eight controls. The mean (±SD) age of the entire cohort (N = 26) was 66 (±10) years. Individuals with a history of radiation had significantly thinner mean SCMF (0.26 [±0.04 mm]) compared to controls (0.48 [±0.06 mm]; P < .05). Individuals with thinner SCMF were more likely to have moderate to severe restriction in lateral neck rotation, a higher PCR, and a higher PAS (P < .05). CONCLUSION: Thinner sternocleidomastoid fascia on ultrasound in patients having undergone radiotherapy for head and neck cancer was associated with reduced lateral neck movement, poorer pharyngeal constriction and greater penetration/aspiration scale. The data suggest that cervical fibrosis is associated with swallowing dysfunction in head and neck cancer survivors and support the notion that, "As the neck goes, so does the swallow." LEVEL OF EVIDENCE: 3. Laryngoscope, 131:548-552, 2021.

Is EAT-10 Useful to Assess Swallowing during the Chemo-Radiotherapy Phase in Patients with Head and Neck Cancer? A Pilot Study.

OBJECTIVE/HYPOTHESIS: The 10-item Eating-Assessment Tool (EAT-10) is a dysphagia screening test. In HNC patients, screening and diagnosis of dysphagia are not well-established. To determine the metrological properties of the EAT-10 compared with videofluoroscopy in non-surgical HNC-patients and to assess the relationship between EAT-10 scores and patients' self-reported symptoms. STUDY DESIGN: Prospective cohort study. METHODS: Forty-six HNC-patients recently diagnosed and referred to chemoradiotherapy (CRT). Main outcome was evidence of dysphagia according to EAT-10 score, self-perception on a Visual Analog Scale (VAS) of impaired swallowing, severity on the Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale (FOIS). Patients were assessed at baseline, before-CRT, after-CRT, and at 3-month follow-up. RESULTS: A strong baseline correlation between EAT-10, VAS, and FOIS was observed. All 3 values decreased in weeks 6 to 9 after CRT initiation; a poor correlation of EAT-10 with VAS was observed at 3-month follow-up. A receiver operating characteristic curve determined new cut-off points (sensitivity/specificity) for safe swallowing: baseline 3 (86%, 77%); post-CRT, 15 (62.5%, 80%); and 3-month follow-up, 4 (83%, 75%). CONCLUSIONS: New safe-swallow EAT-10-points are suggested for this population during screening and the oncological follow-up. A poor correlation between EAT10-score and patient self-reported symptoms was observed at the end-RT and at 3-month follow-up, highlighting the need for an objective evaluation instrument.

Validation of the oral health impact profile - 14 in patients with head and neck cancer

BACKGROUND: The Oral Health Impact Profile-14 (OHIP-14) was designed to assess patients' perception of the impact of oral disorders on their quality of life (QoL). Although the OHIP-14 is now frequently used in patients with head and neck cancer, data related to its measurement properties in this population are scarce. The aim of the present study was to evaluate the reliability and validity of the OHIP-14 in a sample of Serbian patients with head and neck cancer. MATERIAL AND METHODS: Data were available for 345 patients (257 [74.5%] males; aged 30-92 years), with head and neck cancer. All patients completed the OHIP-14 and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35. Factor analyses, internal consistency reliability (i.e., Cronbach’s α coefficient), and construct validity were analyzed. RESULTS: The factor analyses confirmed that 14 OHIP items were measuring a single underlying factor. Cronbach's Alpha coefficient was 0.98 and corrected item-total correlations ranged 0.77-0.93. Lower OHIP-14 scores (i.e., lower impacts on oral health) were more frequently present among patients who had only surgery as a therapeutic procedure compared to those who had surgery accompanied with radio- and chemotherapy (p < 0.01). Patients with a tumor stage 0-II also had lower OHIP-14 scores compared to those who had a tumor stage III-IV (p < 0.01). The OHIP-14 correlated significantly with the QLQ-C30 and QLQ-H&N35 scales. CONCLUSIONS: As a unidimensional instrument, the OHIP-14 provides oral QoL assessments with sound internal consistency reliability and construct validity among patients with head and neck cancer

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Exercise and Nutrition Interventions in Patients with Head and Neck Cancer during Curative Treatment: A Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to examine the effects of nutritional and physical exercise interventions and interventions combining these interventions during radiotherapy treatment for patients with head and neck cancer on body composition, objectively measured physical function and nutritional status. Systematic electronic searches were conducted in MEDLINE (PubMed interface), EMBASE (Ovid interface), CINAHL (EBSCO interface) and Cochrane Library (Wiley interface). We identified 13 randomized controlled trials (RCTs) that included 858 patients. For body composition, using only nutrition as intervention, a significant difference between treatment and control group were observed (SMD 0.42 (95CI 0.23-0.62), p < 0.001). Only pilot RCTs investigated combination treatment and no significant difference between the treatment and control groups were found (SMD 0.21 (95CI -0.16-0.58), p = 0.259). For physical function, a significant difference between treatment and control group with a better outcome for the treatment group were observed (SMD 0.78 (95CI 0.51-1.04), p < 0.001). No effects on nutritional status were found. This meta-analysis found significantly positive effects of nutrition and physical exercise interventions alone in favor of the treatment groups. No effects in studies with combined interventions were observed. Future full-scaled RCTs combining nutrition and physical exercise is warranted.