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This study aimed to explore the application effects of cluster process control and routine nursing on the prevention of pressure injury (PI) in patients undergoing head and neck cancer surgery and to provide a basis for reducing the occurrence of PI, thereby promoting the safety of the patients. This was a retrospective study. Patients with head and neck cancers who underwent surgical treatment in the Department of Otolaryngology at the Second Affiliated Hospital of Fujian Medical University from July 2022 to June 2023 were selected as the research participants. Participants were classified into experimental and control groups using a convenience sampling method. In the experimental group, cluster process control was implemented, while routine nursing management was applied in the control group. The incidence of PI (p = 0.028) and healing time (p = 0.035) in the experimental group were lower than those in the control group. The process management ability of nurses in the experimental group was significantly improved, with the results for the Braden scale (p = 0.023), effective decompression (p = 0.002), floating heel (p = 0.002), nutrition monitoring (p = 0.005), and patient satisfaction in the experimental group being higher than those in the control group (p = 0.007). This study effectively demonstrated the effect of cluster process control in reducing the incidence of PI in patients undergoing head and neck cancer surgery, thereby determining that cluster process control is suitable for clinical application. [ABSTRACT FROM AUTHOR]

In cancer cells, the nuclear transport system is often disrupted, leading to abnormal localization of nuclear proteins and altered gene expression. This disruption can arise from various mechanisms such as mutations in genes that regulate nuclear transport, altered expression of transport proteins, and changes in nuclear envelope structure. Oncogenic protein build-up in the nucleus due to the disturbance in nuclear transport can also boost tumor growth and cell proliferation. In this study, we performed bioinformatic analyses of 23 key nuclear transport receptors using genomic and transcriptomic data from pancancer and head and neck squamous cell carcinoma (HNSCC) datasets from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia and found that the total alteration frequency of 23 nuclear transport receptors in 2691 samples of the PCAWG Consortium was 42.1% and a high levels of genetic alterations was significantly associated with poor overall survival. Amplification was the most common type of genetic alterations, and results in the overexpression of nuclear transport receptors in HNSCC compared to normal tissues. Furthermore, our study revealed that seven out of eight cell cycle genes (CDK1, CDK2, CDK4, CDK6, CCNA1, CCNB1, and CCNE2) were significantly and positively correlated with nuclear transport receptor genes in TCGA pancancer and CCLE datasets. Additionally, functional enrichment analysis showed that nuclear transport receptor genes were mainly enriched in the adhesion junction, cell cycle, ERBB, MAPK, MTOR and WNT signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Therapeutic Radiographers (RT) and Speech and Language Therapists (SLT) work closely together in caring for people with head and neck cancer and need a strong understanding of each others' roles. Peer teaching has been shown to be one of the most effective methods of teaching; however, no studies to date, have involved RT and SLT students. This research aims to establish the effectiveness and perceptions of peer-led teaching between undergraduate RT and SLT students in Ulster University. Methods: Twenty SLT students and 14 RT students participated. Knowledge tests were taken online before the peer-led teaching session (T1), after the session (T2) and 3 months later (T3). Students' perceptions of the experience were collected at the end of the session. Wilcoxon signed-rank tests were used to analyse the impact of the intervention on knowledge scores. Qualitative content analysis was used for open text response data. Results: RT students' own professional knowledge score at T2 was statistically significantly higher than the score at T1; the score at T3 was not deemed to be statistically significantly higher. RT students' SLT knowledge score at T2 and T3 was found to be statistically significantly higher than the score at T1. SLT students' own professional knowledge score was not statistically significantly higher at T2 or T3 than T1. They did have a statistically significantly higher score at T2 on the RT test, but score at T3 was not deemed to be statistically significantly higher. The majority of students across both professions agreed or strongly agreed that the peer-led teaching experience had a positive impact on their learning. Conclusion: This investigation highlights the benefits of an interprofessional peer-led teaching intervention for RT and SLT students and the findings add to the evidence of more objective study of knowledge gain as a result of interprofessional peer teaching. [ABSTRACT FROM AUTHOR]

Background: In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. Material and method: This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. Results: During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008–2012 cohort was 38 days, compared to 22 days for the 2017–2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008–2012, compared to 15 days for the 2017–2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). Conclusions: We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site. [ABSTRACT FROM AUTHOR]

Head and neck cancer treatment often consists of surgical resection of the tumor followed by ionizing radiation (IR), which can damage surrounding tissues and cause adverse side effects. The underlying mechanisms of radiation-induced salivary gland dysfunction are not fully understood, and treatment options are scarce and ineffective. The wound healing process is a necessary response to tissue injury, and broadly consists of inflammatory, proliferative, and redifferentiation phases with immune cells playing key roles in all three phases. In this study, select immune cells were phenotyped and quantified, and certain cytokine and chemokine concentrations were measured in mouse parotid glands after IR. Further, we used a model where glandular function is restored to assess the immune phenotype in a regenerative response. These data suggest that irradiated parotid tissue does not progress through a typical inflammatory response observed in wounds that heal. Specifically, total immune cells (CD45+) decrease at days 2 and 5 following IR, macrophages (F4/80+CD11b+) decrease at day 2 and 5 and increase at day 30, while neutrophils (Ly6G+CD11b+) significantly increase at day 30 following IR. Additionally, radiation treatment reduces CD3- cells at all time points, significantly increases CD3+/CD4+CD8+ double positive cells, and significantly reduces CD3+/CD4-CD8- double negative cells at day 30 after IR. Previous data indicate that post-IR treatment with IGF-1 restores salivary gland function at day 30, and IGF-1 injections attenuate the increase in macrophages, neutrophils, and CD4+CD8+ T cells observed at day 30 following IR. Taken together, these data indicate that parotid salivary tissue exhibits a dysregulated immune response following radiation treatment which may contribute to chronic loss of function phenotype in head and neck cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction/Background: Patients living with and after head and neck cancer often experience treatment-related consequences. Head and neck lymphoedema can be described as a common chronic side effect of head and neck cancer and recognised as a contributing factor to impairment of functional status, symptom burden and health-related quality of life. The effects of head and neck lymphoedema can limit patients' involvement in daily activities and alter their appearance, increasing symptom burden and negatively affecting health-related quality of life. Objective: The protocol outlines the rationale and aims for the systematic review. The main aim of the systematic review is to identify and systematically synthesise the literature on the effectiveness of head and neck lymphoedema management strategies, on both function status and health-related quality of life for head and neck cancer patients. Methods and analysis: This protocol will be conducted according to the PRISMA-P guidelines. Electronic databases will be systematically searched using MEDLINE via Ovid and PubMed, CINAHL, Cochrane Central Register of Controlled Trials and Scopus. Inclusion criteria will involve intervention studies for head and neck lymphoedema management, English language, and adult human participants following head and neck cancer. The software Covidence will be used to export, manage, and screen results. Risk of bias and quality will be assessed in included studies using the Cochrane Handbook of Systematic Reviews of Intervention risk of bias and GRADE tools. A meta-analysis will be performed if there are sufficient homogenous studies. Alternatively, a narrative synthesis will be completed on study findings. Ethics and dissemination: No ethical approval is required as the study does not involve patient and public involvement. The findings of the review will be disseminated in conferences and submitted for approval to be published in a peer-reviewed journal. Prospero registration number: CRD42022378417. (S1 Appendix). [ABSTRACT FROM AUTHOR]

With the increasing focus on patient-centred care, this study sought to understand priorities considered by patients and healthcare providers from their experience with head and neck cancer treatment, and to compare how patients' priorities compare to healthcare providers' priorities. Group concept mapping was used to actively identify priorities from participants (patients and healthcare providers) in two phases. In phase one, participants brainstormed statements reflecting considerations related to their experience with head and neck cancer treatment. In phase two, statements were sorted based on their similarity in theme and rated in terms of their priority. Multidimensional scaling and cluster analysis were performed to produce multidimensional maps to visualize the findings. Two-hundred fifty statements were generated by participants in the brainstorming phase, finalized to 94 statements that were included in phase two. From the sorting activity, a two-dimensional map with stress value of 0.2213 was generated, and eight clusters were created to encompass all statements. Timely care, education, and person-centred care were the highest rated priorities for patients and healthcare providers. Overall, there was a strong correlation between patient and healthcare providers' ratings (r = 0.80). Our findings support the complexity of the treatment planning process in head and neck cancer, evident by the complex maps and highly interconnected statements related to the experience of treatment. Implications for improving the quality of care delivered and care experience of head and cancer are discussed. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy with cisplatin in a triweekly regimen of 100 mg/m2 body surface area, is used to treat locally advanced head and neck squamous cell carcinoma (HNSCC) with curative intent. Cisplatin dose limiting toxicity (CDLT) occurs often and impedes obtaining the planned cumulative cisplatin dose. A cumulative cisplatin dose of 200 mg/m2 or more is warranted for better survival and locoregional control. Patients with a low skeletal muscle mass (SMM) have a three-fold higher risk of developing CDLT than patients with a normal SMM. SMM can be assessed through measurements on routinely performed diagnostic head and neck CT- or MRI-scans. A weekly regimen of 40 mg/m2 body surface area cisplatin is proposed as a less toxic schedule, which possibly decreases the risk of developing CDLT and enables reaching a higher cumulative cisplatin dose. The aim of this multicenter randomized clinical trial (NL76533.041.21, registered in the Netherlands Trial Register) is to identify whether a regimen of weekly cisplatin increases compliance to the planned chemotherapy scheme in HNSCC patients with low SMM. The primary outcome is the difference in compliance rate, defined as absence of CDLT, between low SMM patients receiving either the weekly or triweekly regimen. Secondary outcomes consist of toxicities, the cumulative cisplatin dose, time to recurrence, incidence of recurrence at two years of follow-up, location of recurrence, 2-year overall, disease free and disease specific survival, quality of life, patient's experiences, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicates patients' survivorship outcomes can be enhanced through active engagement in a multi-modal cancer prehabilitation programme (MCPP), although this intervention is not uniformly embedded as a standard of care. MCPP aims to optimise patients physiologically and psychologically for cancer treatments, shorten recovery time, reduce complications, promote healthier lifestyles and improve quality of life. South Eastern Health and Social Care Trust (SET) developed and evaluated a system-wide collaborative approach to MMCP across three tumour groups (colorectal, lung, head and neck cancer). Addressing the lack of qualitative evaluation of MCPPs, this novel paper explores mechanisms promoting feasibility and acceptability of MCPP from patients' and interdisciplinary professionals' perspectives. Methods: Semi-structured virtual one-to-one interviews were conducted with 24 interdisciplinary professionals and nine patients. Transcripts were recorded, transcribed verbatim and themes developed using Framework Analysis. Results: Analysis of findings identified three themes providing an in-depth understanding of key elements required to develop and promote system-wide delivery of a MCPP: 1) Equipping the team: Capability and capacity, 2) Timing of intervention and delivery timeframe and 3) Systems and processes. Conclusion: The system-wide collaborative approach to developing a MCPP was deemed both feasible and acceptable. Success was attributed to visionary leadership, alongside a diverse group of interdisciplinary professionals being engaged, motivated and committed to intervention delivery in an effort to improve patient outcomes. Iterative, responsive troubleshooting during initial delivery is required to facilitate successful implementation. Further training is required for greater adherence to provision of prescriptive high intensity exercise within the programme, which may further promote enhanced patient outcomes. To enable sustainability of MCPP, ongoing training for professionals and funding is required. [ABSTRACT FROM AUTHOR]

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue. [ABSTRACT FROM AUTHOR]

Background and aim: Attempts at personalisation of exercise programmes in head and neck cancer (HaNC) have been limited. The main aim of the present study is to investigate the feasibility and acceptability of introducing a remotely delivered, fully personalised, collaborative, and flexible approach to prescribing and delivering exercise programmes into the HaNC usual care pathway. Methods: This is a single arm, feasibility study. Seventy patients diagnosed with HaNC will be recruited from two regional HaNC centres in the United Kingdom. Patients will undertake an 8-week exercise programme designed and delivered by cancer exercise specialists. The exercise programme will start any time between the time of diagnosis and up to 8 weeks after completing treatment, depending on patient preference. The content of the exercise programme will be primarily based on patient needs, preferences, and goals, but guided by current physical activity guidelines for people with cancer. The primary outcome measure is retention to the study. Secondary quantitative outcomes are uptake to the exercise programme, different measures of exercise adherence, pre- and post-intervention assessments of fatigue (Multidimensional Fatigue Symptom Inventory—Short Form), quality of life (SF-36), physical activity levels (International Physical Activity Questionnaire–Short Form), and various components of physical fitness. The outcomes of the nested qualitative study are acceptability and feasibility of the intervention evaluated via interviews with patients, health care professionals, and the cancer exercise specialists. Intervention and participant fidelity will be determined using checklists and scrutiny of each patient's logbook and the cancer exercise specialists' meeting notes. Analysis of quantitative data will be via standard summary statistics. Qualitative data will be analysed using thematic analysis. Expected results: This feasibility study will inform the design and conduct of a future randomised controlled trial. Success will be defined according to a traffic light system for identifying the appropriateness of progression to a randomised controlled trial. Trial registration: International Standard Randomised Controlled Trial Number registry (ISRCTN82505455). [ABSTRACT FROM AUTHOR]

Importance: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. Objective: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. Design: Retrospective cohort study. Setting: Academic Medical Center (Massachusetts General Hospital, Boston). Participants: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. Measurements: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). Results: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7–5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07–1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24–2.68], P = 0.001). Conclusions and relevance: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival. [ABSTRACT FROM AUTHOR]

Introduction: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). Study design: Registry-based cohort study including only people with rare head and neck cancers. Objectives: to help describe the natural history of rare head and neck cancers; to evaluate factors that influence prognosis; to assess treatment effectiveness; to measure indicators of quality of care. Methods: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. Results: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed. [ABSTRACT FROM AUTHOR]

There are currently no clinical strategies utilizing tumor gene expression to inform therapeutic selection for patients with head and neck squamous cell carcinoma (HNSCC). One of the challenges in developing predictive biomarkers is the limited characterization of preclinical HNSCC models. Patient-derived xenografts (PDXs) are increasingly recognized as translationally relevant preclinical avatars for human tumors; however, the overall transcriptomic concordance of HNSCC PDXs with primary human HNSCC is understudied, especially in human papillomavirus-associated (HPV+) disease. Here, we characterized 64 HNSCC PDXs (16 HPV+ and 48 HPV-) at the transcriptomic level using RNA-sequencing. The range of human-specific reads per PDX varied from 64.6%-96.5%, with a comparison of the most differentially expressed genes before and after removal of mouse transcripts revealing no significant benefit to filtering out mouse mRNA reads in this cohort. We demonstrate that four previously established HNSCC molecular subtypes found in The Cancer Genome Atlas (TCGA) are also clearly recapitulated in HNSCC PDXs. Unsupervised hierarchical clustering yielded a striking natural division of HNSCC PDXs by HPV status, with C19orf57 (BRME1), a gene previously correlated with positive response to cisplatin in cervical cancer, among the most significantly differentially expressed genes between HPV+ and HPV- PDXs. In vivo experiments demonstrated a possible relationship between increased C19orf57 expression and superior anti-tumor responses of PDXs to cisplatin, which should be investigated further. These findings highlight the value of PDXs as models for HPV+ and HPV- HNSCC, providing a resource for future discovery of predictive biomarkers to guide treatment selection in HNSCC. [ABSTRACT FROM AUTHOR]

The membrane-associated RING-CH-type finger ubiquitin ligase MARCHF8 is a human homolog of the viral ubiquitin ligases Kaposi's sarcoma herpesvirus K3 and K5 that promote host immune evasion. Previous studies have shown that MARCHF8 ubiquitinates several immune receptors, such as the major histocompatibility complex II and CD86. While human papillomavirus (HPV) does not encode any ubiquitin ligase, the viral oncoproteins E6 and E7 are known to regulate host ubiquitin ligases. Here, we report that MARCHF8 expression is upregulated in HPV-positive head and neck cancer (HNC) patients but not in HPV-negative HNC patients compared to normal individuals. The MARCHF8 promoter is highly activated by HPV oncoprotein E6-induced MYC/MAX transcriptional activation. The knockdown of MARCHF8 expression in human HPV-positive HNC cells restores cell surface expression of the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2, and enhances apoptosis. MARCHF8 protein directly interacts with and ubiquitinates the TNFRSF death receptors. Further, MARCHF8 knockout in mouse oral cancer cells expressing HPV16 E6 and E7 augments cancer cell apoptosis and suppresses tumor growth in vivo. Our findings suggest that HPV inhibits host cell apoptosis by upregulating MARCHF8 and degrading TNFRSF death receptors in HPV-positive HNC cells. Author summary: Since host cell survival is essential for viruses to replicate persistently, many viruses have evolved to prevent host cell apoptosis. The human papillomavirus (HPV) oncoproteins are known to dysregulate proapoptotic proteins. However, our understanding of detailed mechanisms for HPV to inhibit apoptosis is limited. Here, we report that HPV induces expression of the membrane-associated ubiquitin ligase MARCHF8, which is upregulated in HPV-positive head and neck cancer. MARCHF8 ubiquitinates the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2 for degradation. We further revealed that downregulation of the death receptors by MARCHF8 prevents cancer cell apoptosis and that knockout of MARCHF8 expression significantly inhibits in vivo tumor growth and enhances tumor-free survival of mice transplanted with mouse oral cancer cells expressing HPV16 E6 and E7. These results suggest that virus-induced degradation of death receptors leads to cancer cell survival in HPV-positive head and neck cancer. [ABSTRACT FROM AUTHOR]

Introduction: A thermoplastic mask is the most widely used immobilization device for head and neck cancer patients undergoing radiotherapy. The radiation therapist is the staff responsible to prepare these masks and set-up the patients for treatment, a procedure that requires time, patience, and precision. An understanding of Radiation therapists' perceptions regarding thermoplastic mask use will help design interventions to address challenges encountered in its use. This study explored Radiation therapists' perceptions of thermoplastic mask use for head and neck cancer patients undergoing radiotherapy at Ocean Road Cancer Institute in Tanzania. Material and methods: An exploratory qualitative study design was used to explore thermoplastic mask use for head and neck cancer patients undergoing radiotherapy. Semi-structured in-depth interviews were conducted, involving fifteen Radiation therapists from Ocean Road Cancer Institute in Tanzania between March and May 2021. A thematic analysis method was used to identify themes from data scripts. Results: Four themes emerged that reflected radiation therapists' perceptions of thermoplastic mask use for head and neck cancer immobilization among patients undergoing radiotherapy. Emerged themes were (1) Perceived benefits and limitations of thermoplastic mask use, (2) Refresher training and supervision requirements for effective use, (3) Proper storage for quality maintenance, and (4) Increased financial support and proper budgeting. Conclusion: Participants perceived better patient immobilization with a thermoplastic mask use. However, too often recycling of thermoplastic masks and the long waiting time between thermoplastic mask preparation and treatment delivery limits their effective use. For efficient use of thermoplastic masks, there is a need for Radiation therapists' refresher training and proper supervision, improving the storage system and increasing financial support for procuring new thermoplastic masks. [ABSTRACT FROM AUTHOR]

Background: The dose-limiting effect of CT-assessed low skeletal muscle mass (LSMM) measured at the level of the third cervical vertebra has been found in head and neck cancer patients receiving high-dose cisplatin chemoradiotherapy. The aim of this study was to investigate the predictive factors for dose-limiting toxicities (DLTs) using low-dose weekly chemoradiotherapy. Materials and methods: Head and neck cancer patients receiving definite chemoradiotherapy with weekly 40 mg/m2 body surface area (BSA) cisplatin or paclitaxel 45 mg/m2 BSA and carboplatin AUC2 were consecutively included and retrospectively analysed. Skeletal muscle mass was assessed using the muscle surface at the level of the third cervical vertebra in pretherapeutic CT scans. After stratification for LSMM DLT, acute toxicities and feeding status during the treatment were examined. Results: Dose-limiting toxicity was significantly higher in patients with LSMM receiving cisplatin weekly chemoradiotherapy. For paclitaxel/carboplatin, no significance regarding DLT and LSMM could be found. Patients with LSMM had significantly more dysphagia before treatment, although feeding tube placement before treatment was equal in patients with and without LSMM. Conclusions: LSMM is a predictive factor for DLT in head and neck patients treated with low-dose weekly chemoradiotherapy with cisplatin. For paclitaxel/carboplatin, further research must be carried out. [ABSTRACT FROM AUTHOR]

Background: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. Methods: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. Results: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42–57) vs. 47 (37–52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31–47) vs. 42 (34–47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. Conclusion: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients. [ABSTRACT FROM AUTHOR]

Background: Radiomics involves the extraction of quantitative information from annotated Computed-Tomography (CT) images, and has been used to predict outcomes in Head and Neck Squamous Cell Carcinoma (HNSCC). Subjecting combined Radiomics and Clinical features to Machine Learning (ML) could offer better predictions of clinical outcomes. This study is a comparative performance analysis of ML models with Clinical, Radiomics, and Clinico-Radiomic datasets for predicting four outcomes of HNSCC treated with Curative Radiation Therapy (RT): Distant Metastases, Locoregional Recurrence, New Primary, and Residual Disease. Methodology: The study used retrospective data of 311 HNSCC patients treated with radiotherapy between 2013–2018 at our centre. Binary prediction models were developed for the four outcomes with Clinical-only, Clinico-Radiomic, and Radiomics-only datasets, using three different ML classification algorithms namely, Random Forest (RF), Kernel Support Vector Machine (KSVM), and XGBoost. The best-performing ML algorithms of the three dataset groups was then compared. Results: The Clinico-Radiomic dataset using KSVM classifier provided the best prediction. Predicted mean testing accuracy for Distant Metastases, Locoregional Recurrence, New Primary, and Residual Disease was 97%, 72%, 99%, and 96%, respectively. The mean area under the receiver operating curve (AUC) was calculated and displayed for all the models using three dataset groups. Conclusion: Clinico-Radiomic dataset improved the predictive ability of ML models over clinical features alone, while models built using Radiomics performed poorly. Radiomics data could therefore effectively supplement clinical data in predicting outcomes. [ABSTRACT FROM AUTHOR]

Objectives: In those undergoing treatment for head and neck cancer (HNC), sarcopenia is a strong prognostic factor for outcomes and mortality. This review identified working definitions and methods used to objectively assess sarcopenia in HNC. Method: The scoping review was performed in accordance with Arksey and O'Malley's five-stage methodology and the Joanna Briggs Institute guidelines. Information sources: Eligible studies were identified using MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases. Study selection: Inclusion criteria represented studies of adult HNC patients in which sarcopenia was listed as an outcome, full-text articles written in English, and empirical research studies with a quantitative design. Data extraction: Eligible studies were assessed using a proprietary data extraction form. General information, article details and characteristics, and details related to the concept of the scoping review were extracted in an iterative process. Results: Seventy-six studies published internationally from 2016 to 2021 on sarcopenia in HNC were included. The majority were retrospective (n = 56; 74%) and the prevalence of sarcopenia ranged from 3.8% to 78.7%. Approximately two-thirds of studies used computed tomography (CT) to assess sarcopenia. Skeletal muscle index (SMI) at the third lumbar vertebra (L3) (n = 53; 70%) was the most prevalent metric used to identify sarcopenia, followed by SMI at the third cervical vertebra (C3) (n = 4; 5%). Conclusions: Currently, the most effective strategy to assess sarcopenia in HNC depends on several factors, including access to resources, patient and treatment characteristics, and the prognostic significance of outcomes used to represent sarcopenia. Skeletal muscle mass (SMM) measured at C3 may represent a practical, precise, and cost-effective biomarker for the detection of sarcopenia. However, combining SMM measurements at C3 with other sarcopenic parameters—including muscle strength and physical performance–may provide a more accurate risk profile for sarcopenia assessment and allow for a greater understanding of this condition in HNC. [ABSTRACT FROM AUTHOR]

In this article, we compare the maximum likelihood estimate (MLE) and the maximum product of spacing estimate (MPSE) of a stress-strength reliability model, θ = P(Y < X), under adaptive progressive type-II progressive hybrid censoring, when X and Y are independent random variables taken from the inverse Weibull distribution (IWD) with the same shape parameter and different scale parameters. The performance of both estimators is compared, through a comprehensive computer simulation based on two criteria, namely bias and mean squared error (MSE). To demonstrate the effectiveness of our proposed methods, we used two examples of real-life data based on Breakdown Times of an Insulated Fluid by (Nelson, 2003) and Head and Neck Cancer Data by (Efron, 1988). It is concluded that the MPSE method outperformed the MLE method in terms of bias and MSE values. [ABSTRACT FROM AUTHOR]

Introduction: Mycetoma is a unique neglected tropical disease which is found endemic in areas known as the "mycetoma belt". Head and neck mycetoma is a rarity and it has many devastating impacts on patients and communities. In this study, we assessed clinical findings, investigations, and predictors for recurrence of head and neck mycetoma in Sudan. Methodology: A retrospective study was conducted at Mycetoma Research Center in Khartoum between January 1999 and December 2020 for all patients with head and neck mycetoma. Data were analyzed using R software version 4.0.2. Results: We included 107 patients with head and neck mycetoma. 65.4% were young adult males from mycetoma endemic areas in Sudan, and most of them were students (33.6%). Most of patients (64.4%) had actinomycetoma. Before presenting with head and neck mycetoma, majority (75.7%) had a long duration with mycetoma, and 30.8% had a history of trauma. The commonest invaded site was the parietal region (30.8%). The lesion started gradually in most of the patients (96.3%). 53.3% of the patients had large size lesions with no sweating, regional lymph nodes involvement, or distal vein involvement. CT scan was the most accurate diagnostic tool while 8.4% of patients were diagnosed by clinical examinations only. Laboratory investigations confirmed that 24/45 (44.4%) of actinomycetoma was caused by Streptomyces somaliensis while 13/28 (46.4%) of eumycetoma was caused by Madurella mycetomatis. All patients with recurrence of head and neck mycetoma underwent surgical excision of the lesion (n = 41/41 {100%}, p < 0.001). Conclusion: In head and neck mycetoma, the most common type was actinomycetes in Sudan. Majority had a long course of mycetoma and the commonest causative organism was Streptomyces somaliensis. The treatment outcome was poor and characterized by a low cure rate. Author summary: Head and neck mycetoma is the rarest form of mycetoma. It has devastating impacts on patients, communities, and the health system. The study concludes that: Head and neck Mycetoma -like all mycetoma- mainly affects young adult males in rural areas of Sudan. The disease is diagnosed using numerous radiological methods and investigations alongside clinical examination. Despite the CT scan being the most accurate tool, most patients are diagnosed by clinical tests only; due to the high cost of investigations and financial issues. In this study, all patients with the recurrence of head and neck mycetoma underwent surgical excision of the lesion. The worst thing about the head and neck Mycetoma is that the treatment outcome was poor and characterized by a low cure rate. More attention in is needed regarding mycetoma globally and in Sudan, especially in Gezira and Sinnar states. Therefore, screening by history and clinical examination of Mycetomata's lesions is mandatory for persons living in an endemic regions. [ABSTRACT FROM AUTHOR]

Objectives: The pathologic nodal stage of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) patients is classified according to the number of lymph nodes (LNs), as revised in 2018. Previous studies showed that the LN ratio (LNR) could be also a significant prognostic factor in head and neck cancer, but there are few studies on the LNR in HPV-related [HPV(+)] OPC. The aim of the present study was to analyze the predictive value of the LNR for survival and recurrence in HPV(+) OPC patients. Materials and methods: HPV(+) OPC patients treated with surgery with or without postoperative radiotherapy from January 2000 to March 2019 were evaluated. The patients were divided into two sets of three groups, according to LN numbers based on pathologic nodal stages, and LNRs by a cutoff value of 0.05. The medical records were reviewed, and the overall survival (OS), disease-free survival, locoregional recurrence, and distant metastasis incidence were analyzed. Results: Ninty patients were included and the median follow-up period was 38.2 months. There were no significant differences in OS in the LN number groups. However, there was a significant difference in OS in the LNR groups (P = 0.010). The incidence of distant metastasis in the LNR groups was significantly different (P = 0.005). Conclusion: The LNR in HPV(+) OPC patients may be a more useful tool to predict survival and distant metastasis than the LN number. Additional research and consensus on surgical pathology are needed before applying the LNR to adjuvant treatment decisions and pathologic nodal staging. [ABSTRACT FROM AUTHOR]

In the Ethical considerations subsection of Materials and Methods, the Institutional Review Board number is incorrect. The correct number is: 201900335B0.By Sheng-Wei Chang; Yuan-Hsiung Tsai; Cheng-Ming Hsu; Ethan I. Huang; Geng-He Chang; Ming-Shao Tsai and Yao-Te TsaiReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

The salivary gland can be permanently impaired by radiation treatment for head and neck cancers. Efforts at tissue regeneration have focused on saliva-producing acinar cells. However, myoepithelial cells are also critical to gland function, but mechanisms that regulate their differentiation are poorly defined. To study myoepithelial differentiation, we employed mSG-PAC1 murine salivary gland epithelial cells. We demonstrate that mSG-PAC1 spheroids exhibit phenotypic plasticity between pro-acinar and myoepithelial cell fates. Increased expression of pro-acinar/acinar or myoepithelial RNAs was identified from spheroids cultured under different media conditions by microarray followed by gene-set enrichment analysis. Spheroids cultured with different medium components expressed proteins typical of either acinar or myoepithelial cells, as detected by immunocytochemistry. We demonstrate that the pattern of TAZ expression in the epithelial compartment of the differentiating murine salivary gland correlates with the expression of the myoepithelial marker alpha-SMA, as is the case for TAZ expression in mSG-PAC1 spheroids. Our analysis also indicates that YAP/TAZ target genes are upregulated together with myoepithelial markers. Importantly, siRNA targeting of TAZ expression in mSG-PAC1 spheroids diminished the expression of myoepithelial markers. Our results in this in vitro cell model implicate TAZ signaling in myoepithelial differentiation. [ABSTRACT FROM AUTHOR]

Background and aim: Head and neck cancer patients are vulnerable to various psychological complications due to the effects of both cancer itself and cancer treatment on patients' appearance and physical well-being. Nevertheless, few data have been obtained on effective psychosocial interventions that could protect this group of cancer patients' psychological well-being. Therefore, this three-armed, parallel-group, double-blind, randomized control trial (RCT) aims to evaluate and compare the effects of acceptance and commitment therapy (ACT) and mindfulness-based stress reduction (MBSR) on positive psychology (such as posttraumatic growth [PTG], hope, and optimism), quality of life (QoL), and psychological complications (depression, anxiety, and experiential avoidance) among newly diagnosed head and neck cancer patients. Methods and analysis: This RCT will target newly diagnosed head and neck cancer patients who have been treated only with surgery or who have not yet received any treatment. In total, 120 patients who meet all of the study's inclusion criteria and none of its exclusion criteria will be randomly assigned into three groups—an ACT group, an MBSR group, and a treatment-as-usual control group—at a 1:1:1 allocation ratio. Participants in the two intervention groups (the ACT and MBSR groups) will undergo an eight-week group intervention program. During this program, each intervention will comprise eight modules based on ACT and MBSR, respectively. Outcome assessments will be performed across a three-point timeline, including before the intervention (t0), immediately after the psychosocial intervention at eight weeks (t1), and six months after the intervention (t2). The primary outcome that will be assessed during this RCT is PTG. Meanwhile, the secondary outcomes that will be evaluated in this study are such as QoL, hope, optimism, depression, anxiety, and experiential avoidance. Trial registration number: NCT04800419 (ClinicalTrials.gov). Registered on March 16, 2021. [ABSTRACT FROM AUTHOR]

Drug resistance, either intrinsic or acquired, can impair treatment effects and result in increased cell motility and death. MicroRNA-21 (miR-21), a proto-oncogene, may facilitate the development or maintenance of drug resistance in cancer cells. Restoring drug sensitivity can improve therapeutic strategies, a possibility that requires functional evaluation and mechanistic exploration. For miR-21 detection, matched tissue samples from 30 head and neck squamous cell carcinoma (HNSCC) patients and 8 head and neck cancer (HNC) cell lines were obtained. Reverse transcription-PCR to detect expression, MTT and clonogenic assays to evaluate cell proliferation, apoptosis assays, resazurin cell viability assays, western blot and luciferase reporter assays to detect protein expression, and flow cytometry to analyse the cell cycle were adopted. Compared to the corresponding normal control (NC) tissues, 25 cancer tissues had miR-21 upregulation among the 30 matched pair tissues (25/30, 83.8%); furthermore, among the 8 HNC cell lines, miR-21 expression that was notably upregulated in three: UPCI-4B, UMSCC-1, and UPCI-15B. In both the UMSCC-1 and UPCI-4B cell lines, the miR-21 mimic enhanced cell proliferation with reduced apoptosis and increased viability, whereas the miR-21 inhibitor resulted in the opposite effects (all P<0.001); additionally, miR-21 directly targeted the tumour suppressor phosphatase and tensin homologue (PTEN) and inhibited PTEN expression. Furthermore, the miR-21 mimic induced cisplatin resistance, while the miR-21 inhibitor restored cisplatin sensitivity. Overexpression of miR-21 can enhance cell proliferation, reduce apoptosis, and induce drug resistance by inhibiting PTEN expression. Targeting miR-21 may facilitate cancer diagnosis, restore drug sensitivity, and improve therapeutic effects. [ABSTRACT FROM AUTHOR]

Objectives: Adjuvant radiotherapy is the standard of care in locally advanced head and neck cancers. The radiation field is correlated with the surgical field in the adjuvant radiotherapy setting; therefore, tailoring the irradiation field is reasonable. Materials and methods: We retrospectively analyzed patients with oral cavity and oropharyngeal cancers included in the cancer registry between 2015 and 2019 in the study hospital. Patients who underwent whole-neck irradiation (WNI) were compared with those who underwent lower-neck–sparing (LNS) irradiation. Results: A total of 167 patients with oral cavity and oropharyngeal cancers were included in the study. Cancer recurrence was recorded in 33% of the patients. The rate of recurrence of oral cavity and oropharyngeal cancer at neck level IV was 8%. The 2-year incidence of level IV recurrence was lower in the WNI group than in the LNS group (2% vs. 10%; p = 0.04). The 2-year disease-free survival rates were 75% and 63% in the WNI and LNS groups, respectively (p = 0.08). Conclusion: The rate of level IV recurrence was higher in the LNS group than in the WNI group. Trends of improvement in disease-free survival with lower-neck irradiation suggested that it is premature to consider LNS irradiation as daily practice in patients with oral cavity and oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background and aims: The assessment of supportive care needs and fear of cancer progression are important variables to be considered when evaluating the psychological aspects of cancer patients. However, data on how these variables affect posttraumatic growth (PTG) are lacking. This study aimed to investigate the level of PTG among head and neck cancer (HNC) patients within the first year of cancer diagnosis and to determine the association between unmet supportive care needs, fear of cancer progression, and the level of PTG. Methods: Participants were administered socio-demographic and clinical characteristics questionnaire; the 34-item Supportive Care Needs Survey (SCNS-34) to measure the unmet needs; 12-item Fear of Progression Questionnaire-Short Form (FoP-Q-SF) to measure the fear of progression of cancer; and the Posttraumatic Growth Inventory—Short Form (PTGI-SF) to measure the degree of PTG. Results: A total of 190 HNC participants reported a mean total PTGI-SF score of 39.3 (standard deviation = 9.5). General linear model revealed that higher degree of patients' physical and daily living unmet needs and fear of cancer progression significantly predicted lower PTG, after controlling for sociodemographic and clinical factors. Conclusion: HNC patients within the first year of cancer diagnosis reported a high level of PTG. Despite that, psychosocial intervention for HNC patients should emphasize on counteracting patients' physical and daily living unmet needs and fear of cancer progression to improve the psychological well-being of patients. [ABSTRACT FROM AUTHOR]

Background: Cytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts. Methods: We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody. Results: Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody. Conclusion: These results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6. [ABSTRACT FROM AUTHOR]

Introduction: Individual patient data (IPD) present particular advantages in network meta-analysis (NMA) because interactions may lead an aggregated data (AD)-based model to wrong a treatment effect (TE) estimation. However, fewer works have been conducted for IPD with time-to-event contrary to binary outcomes. We aimed to develop a general frequentist one-step model for evaluating TE in the presence of interaction in a three-node NMA for time-to-event data. Methods: One-step, frequentist, IPD-based Cox and Poisson generalized linear mixed models were proposed. We simulated a three-node network with or without a closed loop with (1) no interaction, (2) covariate-treatment interaction, and (3) covariate distribution heterogeneity and covariate-treatment interaction. These models were applied to the NMA (Meta-analyses of Chemotherapy in Head and Neck Cancer [MACH-NC] and Radiotherapy in Carcinomas of Head and Neck [MARCH]), which compared the addition of chemotherapy or modified radiotherapy (mRT) to loco-regional treatment with two direct comparisons. AD-based (contrast and meta-regression) models were used as reference. Results: In the simulated study, no IPD models failed to converge. IPD-based models performed well in all scenarios and configurations with small bias. There were few variations across different scenarios. In contrast, AD-based models performed well when there were no interactions, but demonstrated some bias when interaction existed and a larger one when the modifier was not distributed evenly. While meta-regression performed better than contrast-based only, it demonstrated a large variability in estimated TE. In the real data example, Cox and Poisson IPD-based models gave similar estimations of the model parameters. Interaction decomposition permitted by IPD explained the ecological bias observed in the meta-regression. Conclusion: The proposed general one-step frequentist Cox and Poisson models had small bias in the evaluation of a three-node network with interactions. They performed as well or better than AD-based models and should also be undertaken whenever possible. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare the prognostic impact of sarcopenia in patients with head and neck cancer (HNC) treated with surgery or radiation. Methods: We systematically searched electronic databases to identify articles reporting the impact of sarcopenia on the prognosis of patients with HNC. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were extracted and pooled. HR according to treatment modality were estimated using random-effects models. Statistical analyses were carried out using the Comprehensive Meta-Analysis software. Results: In total, 18 studies enrolling 3,233 patients were included. Sarcopenia was associated with poor OS in both surgery and radiotherapy groups (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.95–3.21; HR 1.63, 95% CI 1.40–1.90, respectively). The HR was significantly higher in the surgery group than in the radiotherapy group (p = 0.004), with similar results obtained for DFS (HR 2.59, 95% CI 1.56–4.31; HR 1.56, 95% CI 1.24–1.97 for the surgery and radiotherapy groups, respectively) and DSS (HR 2.96, 95% CI 0.73–11.95; HR 2.67, 95% CI 1.51–4.73 for the surgery and RT groups, respectively). Conclusions: Sarcopenia was a poor prognostic factor for HNC, regardless of the treatment modality. However, the adverse effects of sarcopenia on survival were more prominent in the surgery group than in the radiotherapy group. Sarcopenia assessment is required for appropriate treatment decision-making. [ABSTRACT FROM AUTHOR]

Introduction: Besides affecting physical health, Oropharyngeal Dysphagia (OD) entails limitations in daily activities and social participation for both patients and their informal caregivers. The identification of OD-related needs is crucial for designing appropriate person-centered interventions. Aims: To explore and map the literature investigating the care needs related to OD management of adult persons with OD and their informal caregivers during the last 20 years. Methods: A scoping review was conducted and reported following PRISMA guidelines. Five electronic databases and reference lists of eligible publications were searched for original works in English or Italian, published between January 2000 and February 2021. Two independent raters assessed studies' eligibility and extracted data; a third rater resolved disagreements. Extracted care needs were analyzed using a Best fit framework synthesis approach. Results: Out of 2,534 records preliminarily identified, 15 studies were included in the review and 266 care needs were extracted. All studies were conducted in Western countries. Research methods primarily consisted of qualitative interviews and focus groups (14 studies, 93.3%); head and neck cancer was the most frequent cause of patients' dysphagia (8 studies, 53.3%); caregivers' perspective was seldom investigated (5 studies, 33.3%). Both patients and caregivers primarily reported social (N = 77; 28.9%) and practical (N = 67; 25.2%) needs, followed by informational (N = 55; 20.7%) and psychological (N = 54; 20.3%) ones. Only patients reported physical needs (N = 13; 4.9%), while spiritual needs were not cited. Conclusions: The recurrence of personal and social needs besides physical ones highlighted the manifold impact of OD on patients' and caregivers' lives. Larger and more focused studies are required in order to design tools and interventions tailored to patients' and caregivers' needs. [ABSTRACT FROM AUTHOR]

Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in over 600,000 new diagnoses annually. Traditionally, HNCC has been related to tobacco and alcohol exposure; however, over the past decade, a growing number of head and neck cancers are attributed to human papillomavirus (HPV) infection. 5-Aza-2'-deoxycytidine (5-AzaD) was demonstrated as an effective chemotherapeutic agent for acute myelogenous leukaemia. Preclinical data revealed that 5-aza inhibits growth and increases cell death of HPV(+) cancer cells. These effects are associated with reduced expression of HPV genes, stabilization of TP53, and activation of TP53-dependent apoptosis. The aim of the present study is to test the effect of 5-AzaD on growth of human squamous cell carcinoma (FaDu), a HPV(-) and p53 mutated cells, in vitro and in vivo. The effect of 5-AzaD on cell viability, cell cycle progression and induction of apoptosis was tested in vitro. The effect of 5-AzaD on tumour growth in vivo was tested using xenograft mice inoculated with FaDu cells. The results indicated that 5-AzaD reduced cell viability and induced apoptosis in FaDu cells in vitro. In vivo studies revealed that 5-AzaD suppresses the growth of tumours in xenograft mice inoculated with FaDu cells through inhibition of proliferation and induction of apoptosis. These findings may emphasis that 5-AzaD is effective in treatment of HPV(-) HNSCC tumours through TP53 independent pathway. Future studies are needed in order to clarify the molecular mechanism of action of 5-AzaD in HPV(-) cancer cells. [ABSTRACT FROM AUTHOR]

Background: This novel meta-analysis was conducted to systematically and comprehensively evaluate the prognostic role of the pretreatment PNI in patients with head and neck neoplasms (HNNs) undergoing radiotherapy. Methods: Three databases, PubMed, Embase, and Web of Science, were used to retrieve desired literature. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled by fixed-effects or random-effects models to analyze the relationship between the PNI and survival outcomes: overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Results: Ten eligible studies involving 3,458 HNN patients were included in our analysis. The robustness of the pooled results was ensured by heterogeneity tests (I2 = 22.6%, 0.0%, and 0.0% for OS, DMFS, and PFS, respectively). The fixed-effects model revealed a lower pretreatment PNI was significantly related to a worse OS (HR = 1.974; 95% CI: 1.642–2.373; P<0.001), DMFS (HR = 1.959; 95% CI: 1.599–2.401; P<0.001), and PFS (HR = 1.498; 95% CI: 1.219–1.842; P<0.001). The trim-and-fill method (HR = 1.877; 95% CI: 1.361–2.589) was also used to prove that the existing publication bias did not deteriorate the reliability of the relationship. Conclusion: The pretreatment PNI is a promising indicator to evaluate and predict the long-term prognostic survival outcomes in HNN patients undergoing radiotherapy. [ABSTRACT FROM AUTHOR]

Purposes: Although clinical and radiological examinations can be used to diagnose oral cancer, and surgical pathology remains the gold standard, these conventional methods have limitations. We evaluated the feasibility of longitudinal next-generation sequencing-based liquid biopsy for oral squamous cell carcinoma surveillance. Materials and methods: Eleven patients were enrolled, and plasma and saliva were collected before, and 1, 3, and 6 months after surgery. Tumor-specific mutations were selected using paired, whole-exome analyses of tumor tissues and whole blood. Genes frequently mutated in head and neck cancer were identified using the Cancer Genome Atlas (TCGA) and Catalogue of Somatic Mutations in Cancer (COSMIC) databases to design targeted deep sequencing panels. Results: In five of the six patients with recurrent cancer, circulating tumor DNA (ctDNA) was detected earlier with liquid biopsy than with conventional monitoring techniques. Moreover, patients without recurrence exhibited decreased ctDNA allele frequency post-treatment. Conclusions: Longitudinal liquid biopsy of plasma and saliva may be feasible for detecting somatic mutations associated with oral squamous cell carcinomas. It might be attributable to determine early tumor recurrence through genetic analysis of ctDNA. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of using skeletal muscle mass (SMM) at C3 (C3 SMM) as a diagnostic marker for sarcopenia in head and neck cancer (HNC) patients. Methods: We evaluated 165 HNC patients and 42 healthy adults who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans. The paravertebral muscle area at C3 and skeletal muscle area at L3 were measured by CT. Pearson's correlation was used to assess the relationship between L3 and C3 SMMs. The prediction model for L3 SMM was developed by multiple linear regression. Then the correlation and the agreement between actual and predicted L3 SMMs were assessed. To evaluate the diagnostic value of C3 SMM for sarcopenia, the receiver operating characteristics (ROC) curves were analyzed. Results: Of the 165 HNC patients, 61 (37.0%) were sarcopenic and 104 (63.0%) were non-sarcopenic. A very strong correlation was found between L3 SMM and C3 SMM in both healthy adults (r = 0.864) and non-sarcopenic patients (r = 0.876), while a fair association was found in sarcopenic patients (r = 0.381). Prediction model showed a very strong correlation between actual SMM and predicted L3 SMM in both non-sarcopenic patients and healthy adults (r > 0.9), whereas the relationship was moderate in sarcopenic patients (r = 0.7633). The agreement between two measurements was good for healthy subjects and non-sarcopenic patients, while it was poor for sarcopenic patients. On ROC analysis, predicted L3 SMM showed poor diagnostic accuracy for sarcopenia. Conclusions: A correlation between L3 and C3 SMMs was weak in sarcopenic patients. A prediction model also showed a poor diagnostic accuracy. Therefore, C3 SMM may not be a strong predictor for L3 SMM in sarcopenic patients with HNC. [ABSTRACT FROM AUTHOR]

Background: Rates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment. Methods: A case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes. Results: In crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases. Conclusions: Salivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the risk and time trends of herpes zoster among patients with head and neck cancer, with or without radiotherapy. Methods: A total of 2160 patients with head and neck cancer were enrolled. The radiotherapy and non- radiotherapy cohorts were frequency-matched at a 1:1 ratio according to sex, age, and index date. Moreover, 1080 matched non-cancer individuals were considered normal controls. Data were obtained from the National Health Insurance Research Database and Cancer Registry. The primary end point was the incidence of herpes zoster, and the adjusted confounding factors were age, sex, comorbidities, oncological surgery, and chemotherapy. Results: The incidence of herpes zoster was higher in cancer patients than in non-cancer individuals but did not significantly differ (13.67 vs. 8.06 per 1,000 person-years, p = 0.18). The risk of herpes zoster was significantly higher in the radiotherapy cohort than in the non-radiotherapy cohort (18.55 vs. 9.06 per 1,000 person-years, p = 0.03). The 5-year incidence rates in the radiotherapy and non-radiotherapy cohorts were 8.9% and 5%, respectively (p < 0.0001). Survival analysis indicated there was no immortal time bias. The time trends in the radiotherapy cohort persistently showed a high risk within the first 2 years, which decreased thereafter. Only patients with comorbid rheumatoid arthritis showed a significantly high risk of herpes zoster (p = 0.02). Oncological surgery and chemotherapy had no impact on the development of herpes zoster. Conclusions: This nationwide population-based study showed that patients with head and neck cancer receiving radiotherapy are at an increased risk of herpes zoster. Health care professionals should pay more attention to this vulnerable group to improve their quality of life. [ABSTRACT FROM AUTHOR]

Background: A typical assessment for sarcopenia involves the use of abdominal computed tomography (CT) for calculating the skeletal muscle index (SMI) at the level of the third lumbar vertebra (L3). However, abdominal CT is not regularly performed on patients with head and neck cancer (HNC). We investigated whether masticatory SMI (M-SMI) measurements based on head and neck CT scans can be used to conduct sarcopenia assessments by evaluating whether M-SMI is correlated with L3-SMI. Methods: Abdominal and head and neck CT images of patients with trauma (n = 50) and HNC (n = 52) were analyzed retrospectively. Both manual delineation and threshold selection methods were used to measure cross-sectional areas of masticatory muscles and those of muscles at the L3 level on CT images. Muscle cross-sectional areas were normalized to height squared to calculate SMI, and a multivariate linear regression model was established to evaluate the correlation between the M-SMI and L3-SMI. Receiver operating characteristic curve analysis was used to assess the ability of the M-SMI to identify sarcopenia, and Cox logistic regression was used to identify predictors of sarcopenia. Results: Patients with HNC had significantly lower M-SMI and L3-SMI than did patients with trauma (p = 0.011 and 0.03, respectively). M-SMI and L3-SMI were strongly correlated (r = 0.901, p < 0.001); in the multivariate model that included sex, the correlation was stronger (r = 0.913, p < 0.001). The associations of sarcopenia with a lower M-SMI (p < 0.001), male sex (p = 0.028), and advanced age (p = 0.011) were significant, and multivariate logistic analysis demonstrated that an M-SMI of <5.5 was an independent predictor of sarcopenia (hazard ratio = 5.37, p < 0.001). Conclusions: M-SMI assessment in routine head and neck CT scans is feasible and can be an alternative for detecting sarcopenia in patients with HNC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholesterol by inhibiting HMG-CoA reductase (HMGCR). Results from some observational studies suggest that statin use may reduce HNSCC risk. We appraised the relationship of genetically-proxied cholesterol-lowering drug targets and other circulating lipid traits with oral (OC) and oropharyngeal (OPC) cancer risk using two-sample Mendelian randomization (MR). For the primary analysis, germline genetic variants in HMGCR, NPC1L1, CETP, PCSK9 and LDLR were used to proxy the effect of low-density lipoprotein cholesterol (LDL-C) lowering therapies. In secondary analyses, variants were used to proxy circulating levels of other lipid traits in a genome-wide association study (GWAS) meta-analysis of 188,578 individuals. Both primary and secondary analyses aimed to estimate the downstream causal effect of cholesterol lowering therapies on OC and OPC risk. The second sample for MR was taken from a GWAS of 6,034 OC and OPC cases and 6,585 controls (GAME-ON). Analyses were replicated in UK Biobank, using 839 OC and OPC cases and 372,016 controls and the results of the GAME-ON and UK Biobank analyses combined in a fixed-effects meta-analysis. We found limited evidence of a causal effect of genetically-proxied LDL-C lowering using HMGCR, NPC1L1, CETP or other circulating lipid traits on either OC or OPC risk. Genetically-proxied PCSK9 inhibition equivalent to a 1 mmol/L (38.7 mg/dL) reduction in LDL-C was associated with an increased risk of OC and OPC combined (OR 1.8 95%CI 1.2, 2.8, p = 9.31 x10-05), with good concordance between GAME-ON and UK Biobank (I2 = 22%). Effects for PCSK9 appeared stronger in relation to OPC (OR 2.6 95%CI 1.4, 4.9) than OC (OR 1.4 95%CI 0.8, 2.4). LDLR variants, resulting in genetically-proxied reduction in LDL-C equivalent to a 1 mmol/L (38.7 mg/dL), reduced the risk of OC and OPC combined (OR 0.7, 95%CI 0.5, 1.0, p = 0.006). A series of pleiotropy-robust and outlier detection methods showed that pleiotropy did not bias our findings. We found limited evidence for a role of cholesterol-lowering in OC and OPC risk, suggesting previous observational results may have been confounded. There was some evidence that genetically-proxied inhibition of PCSK9 increased risk, while lipid-lowering variants in LDLR, reduced risk of combined OC and OPC. This result suggests that the mechanisms of action of PCSK9 on OC and OPC risk may be independent of its cholesterol lowering effects; however, this was not supported uniformly across all sensitivity analyses and further replication of this finding is required. Author summary: Author summary This study aimed to determine if genetically-proxied cholesterol-lowering drugs (such as statins which target HMGCR) and genetically-proxied circulating lipid traits (e.g., low-density lipoprotein cholesterol) have a causal effect on oral and oropharyngeal cancer risk. There was little evidence that genetically-proxied inhibition of HMGCR (target of statins), NPC1L1 (target of ezetimibe) and CETP (target of CETP inhibitors) influences oral or oropharyngeal cancer risk. Similarly, there was little evidence of an effect of circulating lipid traits on oral or oropharyngeal cancer risk. We did find some evidence that genetically-proxied inhibition of PCSK9 increases, while lipid-lowering variants in LDLR reduce oral and oropharyngeal cancer risk. Our findings suggest that the results of previous observational studies examining the effect of statins on oral and oropharyngeal risk may have been confounded. The mechanism of action of PCSK9 may be independent of cholesterol-lowering, however further replication of this finding in other head and neck cancer datasets is required. [ABSTRACT FROM AUTHOR]

Tobacco smoking is associated with an increased risk of oral leukoplakia and head and neck cancer. Although it has recently been reported that the establishment of an immunosuppressive microenvironment in oral potentially malignant disorders may lead to malignant transformation, it is unclear whether the microenvironments of oral potentially malignant disorders differ according to smoking status. We examined differences in programmed death-ligand 1 (PD-L1) expression and subepithelial CD163+ TAM and CD8+ cell/lymphocyte counts in the microenvironment of oral leukoplakia of smoking and non-smoking patients and investigated their associations with malignant transformation. Pathology reports and original biopsy request forms from 1995–2015 were retrospectively reviewed. Lesions clinically characterized as white plaques/lesions of the oral mucosa and pathologically diagnosed as oral epithelial dysplasia were included. Immunohistochemistry was performed to evaluate PD-L1 expression and subepithelial CD163+/CD8+ cell counts. The significance of prognostic factors in predicting malignant transformation was determined using Cox regression analysis. Statistical significance was defined as P<0.05. In total, 200 patients with oral leukoplakia were selected. The mean age at diagnosis was higher in non-smoking patients (n = 141; 66.9 years) than in smoking patients (n = 59; 60.5 years). The 5-year cumulative malignant transformation rate was higher in non-smoking patients than in smoking patients (9.3% vs. 3.0%, respectively). Oral leukoplakia was associated with significantly higher PD-L1 expression and increased numbers of subepithelial CD163+ cells in the non-smoking group compared with the smoking group. Non-smoking-related oral leukoplakia with positive PD-L1 expression was associated with a 6.97-fold (95% confidence interval: 2.14–22.7) increased risk of malignant transformation. The microenvironment of oral leukoplakia differed according to smoking status. A combination of smoking status and PD-L1 expression may predict malignant transformation in oral leukoplakia patients. This study highlights the importance of understanding the interaction between smoking and the microenvironment in oral leukoplakia. [ABSTRACT FROM AUTHOR]

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: Oral mucositis (OM) is a common, painful side effect of radiation therapy used for the treatment of head and neck cancer (HNC). Activation of the innate immune system upon irradiation has been identified as a key precipitating event of OM. To better understand OM's pathogenesis, we studied pattern recognition receptors (PRRs) and their downstream pro-inflammatory cytokines in a mouse model of radiation-induced OM. We also tested therapeutic efficacy of GM-1111 that targets innate immune system to reduce radiation-induced OM. Methods and materials: The pathogenesis of OM was studied in a single X-ray induced mouse model. The severity of OM was measured by visual and microscopical examinations. The irradiation-induced changes of PRRs and their downstream effector cytokine gene expression levels were determined. The efficacy of GM-1111 to reduce OM was tested in single and fractionated irradiation mouse models. The impact of the drug on tumor response to radiation therapy was also tested in a mouse model of human HNC. Results: Radiation-induced tissue ulcerations were radiation-dosage and -time dependent. The lesions showed selective increases in PRR and pro-inflammatory cytokine gene expression levels. Once daily administration of GM-1111 (≥30 mg/kg, s.c.) significantly reduced the severity and the incidence of OM. The drug had little effect on PRRs but significantly inhibited downstream pro-inflammatory cytokine genes. GM-1111 did not interfere radiation therapy to induce HNC SCC-25 tumor regression. Instead, we observed significant drug-induced tumor regression. Conclusions: Radiation induces tissue damages. The increased expression levels of PRRs and their downstream pro-inflammatory cytokine genes in the damaged tissues suggest their important contribution to the pathogenesis of OM. Drug GM-1111 that targets these innate immune molecules may be a potential drug candidate as an intervention for OM. [ABSTRACT FROM AUTHOR]

Distinguishing lung squamous cell carcinoma (LSQCC) from a solitary metastatic lung tumor (MSQCC) from head and neck squamous cell carcinoma (HNSQCC) presents a difficult diagnostic challenge even after detailed pathological assessment. Treatment options and estimated survival outcomes after pulmonary resection differ between patients with LSQCC and MSQCC. This study aimed to investigate whether microRNA (miRNA) profiling by RNA sequencing of HNSQCC, MSQCC, and LSQCC was useful for differential diagnosis of MSQCC and LSQCC. RNA sequencing was performed to identify bioinformatically significant miRNAs from a formalin-fixed paraffin-embedded (FFPE) block from a derivation set. MiRNA levels were confirmed by validation sets using FFPE samples and serum extracellular vesicles from patients. Step-wise discriminant analysis and canonical discriminant analysis identified 13 miRNAs by which the different expression patterns of LSQCC, MSQCC, and HNSQCC groups were demonstrated. Six miRNAs (miR-10a/28/141/320b/3120) were assessed in validation sets, and 4 miRNAs (miR-10a/28/141/3120) were significantly upregulated in LSQCCs compared with MSQCCs and HNSQCCs. Serum extracellular vesicles from LSQCC patients demonstrated significantly elevated miR-10a (p =.042), miR-28 (p =.041), and miR-3120 (p =.047) levels compared with those from MSQCC patients. RNA sequencing is useful for differential diagnosis of LSQCC and MSQCC, and the expression level of miR-10a, miR-28, and miR-3120 in serum extracellular vesicles are promising noninvasive tools for this purpose. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck cancer is a deadly cancer that ranks among the six most common cancers worldwide. The HPV vaccine has been used to prevent head and neck cancer of the oropharynx, and changes in health policies and state law are impacting the role of dental professionals in HPV vaccination. However, relatively little is known about dental professionals' attitudes regarding the vaccine. Objectives: Our study assesses dental professionals' willingness to administer the HPV vaccine, their confidence discussing HPV with patients, beliefs about the vaccine's efficacy, perceived barriers to administering it, and sites of referral. Methods: We surveyed 623 dental professionals, including dentists, hygienists, dental students, and hygiene students across Michigan. Attitudes toward the vaccine and predictive characteristics were evaluated by logistic regression, ANOVAs, and t-tests. Results: The majority of the respondents (51% of dentists, 63% of hygienists, 82% of dental students, and 71% of hygiene students) were willing to administer the HPV vaccine if allowed by law. The role of dental and dental hygiene students would be one of advocacy, educating and recommending the vaccine, and the dental students administering it once licensed. Dental professionals were variably confident discussing HPV with patients and generally believed it enhanced patients' health. Stronger confidence and beliefs were associated with greater willingness to administer the vaccine. Barriers among professionals opposing the HPV vaccine included lack of knowledge on the subject, liability concerns, and personal beliefs. Conclusion: Dental professionals can become leaders in preventing HPV-related cancers. Training and continuing education courses could enhance their confidence and willingness to recommend and administer the HPV vaccine. Policy implications: Legislation that permits dental professionals to administer the vaccine could increase the vaccine's accessibility to patients, improve vaccination rates, and population health. [ABSTRACT FROM AUTHOR]

Background: To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT). Methods: We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups. Results: The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29–16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09). Conclusions: HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years. [ABSTRACT FROM AUTHOR]

This study aimed to update and, if necessary, revise the Gothenburg Trismus Questionnaire (GTQ), the only existing trismus-specific questionnaire, and retest its psychometric properties. Semi-structured interviews were performed with 10 trismus patients of which 5 had head and neck cancer (HNC) and 5 suffered from benign temporomandibular disorders. Trismus was defined as a maximal incisal opening of ≤ 35mm. An expert panel discussed and revised the GTQ based on interview information, expertise knowledge and the original questionnaire. The revised questionnaire was then tested in a study sample consisting of benign jaw-related conditions (n = 26), patients treated for HNC (n = 90) and an age- and gender-matched control group with no trismus (n = 116). The revised version of the GTQ (GTQ 2) was well accepted by patients. The original three domains continued to show high internal consistency (Cronbach's alpha 0.74–0.94) and construct validity. Two dually posed single items were split into four questions and the wording was altered in another three items. Moreover, a new domain (Facial pain) was identified, which had excellent internal consistency (α = 0.96) and good construct validity. The revision of the original Gothenburg Trismus Questionnaire (GTQ 1) with inclusion of patient-input, resulted in splitting of ambiguous items, identifying a fourth domain named Facial pain and the recall time shortened for some items. Additionally, the remaining domains and items were re-confirmed as strong in the psychometric analysis. Henceforth, the new version, GTQ 2 should be used. [ABSTRACT FROM AUTHOR]

Purpose: Non-traumatic osteonecrosis of the femoral head (ONFH) is a plausible complication in brain tumor patients. Frequent use of corticosteroid therapy, chemotherapy, and oxidative stress for managing brain tumors may be associated with the development of ONFH. However, there is little knowledge on the prevalence and risk factors of ONFH from brain tumor. This study aimed to investigate the prevalence and risk factors of ONFH in patients with primary brain tumors. Methods: This retrospective cohort study included data from consecutive patients between December 2005 and August 2016 from a tertiary university hospital in South Korea. A total of 73 cases of ONFH were identified among 10,674 primary brain tumor patients. After excluding subjects (25 out of 73) with missing data, history of alcohol consumption or smoking, history of femoral bone trauma or surgery, comorbidities such as systemic lupus erythematosus (SLE), sickle cell disease, cancer patients other than brain tumor, and previous diagnosis of contralateral ONFH, we performed a 1:2 propensity score-matched, case–control study (ONFH group, 48; control group, 96). Risk factors of ONFH in primary brain tumor were evaluated by univariate and multivariate logistic regression analyses. Results: The prevalence of ONFH in patients with surgical resection of primary brain tumor was 683.9 per 100,000 persons (73 of 10,674). In this cohort, 55 of 74 patients (74.3%) underwent THA for ONFH treatment. We found that diabetes was an independent factor associated with an increased risk of ONFH in primary brain tumor patients (OR = 7.201, 95% CI, 1.349–38.453, p = 0.021). There was a significant difference in univariate analysis, including panhypopituitarism (OR = 4.394, 95% CI, 1.794–11.008, p = 0.002), supratentorial location of brain tumor (OR = 2.616, 95% CI, 1.245–5.499, p = 0.011), and chemotherapy (OR = 2.867, 95% CI, 1.018–8.069, p = 0.046). Conclusions: This study demonstrated that the prevalence of ONFH after surgical resection of primary brain tumor was 0.68%. Diabetes was an independent risk factor for developing ONFH, whereas corticosteroid dose was not. Routine screening for brain tumor-associated ONFH is not recommended; however, a high index of clinical suspicion in these patients at risk may allow for early intervention and preservation of the joints. [ABSTRACT FROM AUTHOR]

Background: Survivors of Head and Neck Cancer experience specific problems in functional performance. The aim of this study was to obtain the test-retest reliability of measurements on Maximal Mouth Opening (MMO), shoulder and neck function, lower and upper body strength, level of mobility and walking ability. Materials and methods: Test-retest study design. Measurements on MMO (intra- and extra orally), Active range of motion of shoulders and neck, 30 Seconds Chair Stand Test, Grip Strength, Timed Up and Go test, and Six Minute Walk test. Results: In total 50 participants were included. The mean age was 68.6. ± 9.9 years and median time since end of treatment was 3.0 years (Q1–Q3: 1.0–5.25 years). We found good to excellent test-retest reliability on the core set of measurements (Intraclass Correlation Coefficient (ICC) 0.77 to 0.98). Measurement of MMO with cardboard card, forward flexion shoulder and Six Minute Walk test had a relatively small measurement error (Smallest Detectable Change (SDC) % 5.4% - 15.1%). Measurement of MMO with a caliper, shoulder abduction, shoulder external rotation, later flexion and rotation of the neck, grip strength, 30 Seconds Chair Stand Test, and Timed up and Go test had a relatively large measurement error (SDC% 19.8% - 44.7%). Conclusion: This core set of measurements on physical performance is found reliable and therefore able to differentiate in physical performance. The reported measurement errors should be taken into consideration when interpreting the results of repeated measurements. Implications for cancer survivors: A core set of physical measurements can be used to measure physical performance in survivors of Head and Neck Cancer. [ABSTRACT FROM AUTHOR]