Development of a high dimensional imaging mass cytometry panel to investigate spatial organization of tissue microenvironment in formalin-fixed archival clinical tissues.

To decipher the interactions between various components of the tumor microenvironment (TME) and tumor cells in a preserved spatial context, a multiparametric approach is essential. In this pursuit, imaging mass cytometry (IMC) emerges as a valuable tool, capable of concurrently analyzing up to 40 parameters at subcellular resolution. In this study, a set of antibodies was selected to spatially resolve multiple cell types and TME elements, including a comprehensive panel targeted at dissecting the heterogeneity of cancer-associated fibroblasts (CAF), a pivotal TME component. This antibody panel was standardized and optimized using formalin-fixed paraffin-embedded tissue (FFPE) samples from different organs/lesions known to express the markers of interest. The final composition of the antibody panel was determined based on the performance of conjugated antibodies in both immunohistochemistry (IHC) and IMC. Tissue images were segmented employing the Steinbock framework. Unsupervised clustering of single-cell data was carried out using a bioinformatics pipeline developed in R program. This paper provides a detailed description of the staining procedure and analysis workflow. Subsequently, the panel underwent validation on clinical FFPE samples from head and neck squamous cell carcinoma (HNSCC). The panel and bioinformatics pipeline established here proved to be robust in characterizing different TME components of HNSCC while maintaining a high degree of spatial detail. The platform we describe shows promise for understanding the clinical implications of TMA heterogeneity in large patient cohorts with FFPE tissues available in diagnostic biobanks worldwide.

Plasma IL-1 and IL-6 Family Cytokines with Soluble Receptor Levels at Diagnosis in Head and Neck Squamous Cell Carcinoma: High Levels Predict Decreased Five-Year Disease-Specific and Overall Survival.

Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (-) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(-) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy.

The TP53 Codon 72 Arginine Polymorphism Is Found with Increased TP53 Somatic Mutations in HPV(-) and in an Increased Percentage among HPV(+) Norwegian HNSCC Patients.

BACKGROUND: Somatic TP53 mutations are frequent in head and neck squamous cell carcinoma (HNSCC) and are important pathogenic factors. OBJECTIVE: To study TP53 mutations relative to the presence of human papillomavirus (HPV) in tumors in HNSCC patients. METHODS: Using a custom-made next-generation sequencing (NGS) panel on formalin-fixed, paraffin-embedded tumor tissue, we analyzed somatic TP53 mutations and the TP53 single-nucleotide polymorphism (SNP) codon 72 (P72R; rs1042522) (proline → arginine) from 104 patients with HNSCC. RESULTS: Only 2 of 44 patients with HPV-positive (HPV(+)) HNSCC had a TP53 somatic mutation, as opposed to 42/60 HPV-negative (HPV(-)) HNSCC patients (p < 0.001). Forty-five different TP53 somatic mutations were detected. Furthermore, in HPV(-) patients, we determined an 80% prevalence of somatic TP53 mutations in the TP53 R72 polymorphism cohort versus 40% in the TP53 P72 cohort (p = 0.001). A higher percentage of patients with oral cavity SCC had TP53 mutations than HPV(-) oropharyngeal (OP) SCC patients (p = 0.012). Furthermore, 39/44 HPV(+) tumor patients harbored the TP53 R72 polymorphism in contrast to 42/60 patients in the HPV(-) group (p = 0.024). CONCLUSIONS: Our observations show that TP53 R72 polymorphism is associated with a tumor being HPV(+). We also report a higher percentage of somatic TP53 mutations with R72 than P72 in HPV(-) HNSCC patients.

The Romberg sign, unilateral vestibulopathy, cerebrovascular risk factors, and long-term mortality in dizzy patients.

Objectives: Describe the relationship between unsteadiness, canal paresis, cerebrovascular risk factors, and long-term mortality in patients examined for dizziness of suspected vestibular origin. Study design: Observational cohort with prospective collection of survival data. Setting: University clinic neurotological unit. Patients: Consecutive patients aged 18-75 years examined in the period 1992-2004 for dizziness of suspected vestibular origin. Outcome measures: Overall survival. Standardized mortality ratio (SMR). Factors: Unsteadiness, canal paresis, age, sex, patient-reported diabetes, hypertension, heart disease, stroke, or TIA/minor stroke. Patients were classified as steady or unsteady based on static posturography at baseline compared to normative values. Results: The study included 1,561 patients with mean age 48 years and 60 % females. Mean follow-up was 22 years. Unsteadiness was associated with higher age, heart disease, diabetes, hypertension, and cerebrovascular dizziness. There were 336 deaths over 31,335 person-years (SMR 0.96; 95 % confidence interval: 0.86-1.07). Canal paresis was not related to unsteadiness (chi square: p = 0.46) or to mortality (unadjusted Cox hazard ratio: 1.04, 95% CI: 0.80-1.34). Unsteadiness was an independent predictor of mortality (adjusted Cox hazard ratio: 1.44, 95% CI: 1.14-1.82). Conclusions: Unsteadiness measured by static posturography is associated with higher age, known cerebrovascular risk factors, and with increased long-term mortality, but not with canal paresis in patients evaluated for dizziness. The study highlights the importance of evaluating patients with conspicuous postural instability for non-vestibular causes.

Tumor Infiltration Levels of CD3, Foxp3 (+) Lymphocytes and CD68 Macrophages at Diagnosis Predict 5-Year Disease-Specific Survival in Patients with Oropharynx Squamous Cell Carcinoma.

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Oropharyngeal (OP) cancers are of special interest because of possible underlying HPV infection which is tied to prognosis. Influxes of inflammatory cells into tumors may vary with prognoses. We wanted to study whether the number of tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) in tumors correlated to HPV status and predicted 5-year disease-specific survival (DSS). Formalin-fixed paraffin-embedded (FFPE) biopsies cut sections from 170 patients treated for OP cancer were stained by immunohistochemistry and evaluated for the number of CD68 (+) TAMs, CD3 (+), and Foxp3 (+) (T regulatory) TILs. From FFPE slides HPV by PCR and p16 by immunohistochemistry were established. From FFPE Hematoxylin-Eosin slides, levels of tumor nuclear polymorphism, tumor invasion, desmoplasia, and inflammation were determined as previously published. Levels of TIL CD3 (+) and TIL Foxp3 (+) were increased among the HPV (+) compared to the HPV (-) patients. High levels of TIL Foxp3 (+) and CD68 (+) macrophages predicted better 5-year DSS. TIL Foxp3 (+) levels predicted independent of age, gender, TNM stage, and HPV infection as well as level of stromal desmoplasia, tumor invasion, and nuclear polymorphism, but more pronounced among tumor HPV (+) than HPV (-) patients.

Psychometric properties of the Norwegian translation of the Tinnitus Handicap Inventory (THI-NOR).

OBJECTIVE: To assess the psychometric properties of a Norwegian translation of the Tinnitus Handicap Inventory (THI-NOR). DESIGN: A survey was sent by post to patients referred with tinnitus as their main complaint to an audiology department. Patients completed a Norwegian version of the Tinnitus Handicap Inventory (THI-NOR), a Norwegian translation of two revised subscales of the Abbreviated profile of hearing aid benefit (APHAB), the General Health Questionnaire (GHQ-12) as well as questionnaires measuring coping expectancies (TOMCATS) and neuroticism (EPI). STUDY SAMPLE: Ninety-nine persons with tinnitus. RESULTS: No associations were found between THI-scores or pure-tone audiometry, gender or age. The proposed subscales of the original THI were not formed by responses from responders. The total scale shows good psychometric properties. Significant correlations were found between distress as measured by the GHQ-12, coping expectancies as measured by TOMCATS and neuroticism as measured by EPI and THI scores. CONCLUSIONS: THI-NOR has psychometric properties similar to those of the Danish translation (THI-DK), from which it was adapted, and to the original THI. THI-NOR seems to be a valid measure of the impact of tinnitus on a person's everyday life. Findings show that the suggested subscales of the questionnaire should be interpreted with caution.

Psychometric properties for the Norwegian translations of two revised APHAB-subscales and an adapted IOI-HA (IOI-CI) in patients with cochlear implants.

OBJECTIVE: The objective was to examine the psychometric properties of two questionnaires in Norwegian for the self-assessment of satisfaction following cochlear implantation. DESIGN: The International Outcome Inventory for Hearing Aids adapted for cochlear implants (IOI-CI) and two revised subscales from the Norwegian translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) were applied. Internal consistency was tested using Cronbach's α. Testing of psychometric properties included the calculation of inter-item correlations and corrected item-total correlations. Spearman's rho was used to investigate associations. Exploratory principal component analyses with Kaiser normalisation were performed. STUDY SAMPLE: One hundred and twenty-one patients (51 males) with cochlear implants (27-88 years, M = 59). RESULTS: For IOI-CI, Cronbach's α was 0.79. Corrected item-total correlations ranged from 0.29 to 0.69. The factor analysis revealed two components. For APHAB, Cronbach's α was 0.91. Two components were revealed by the factor analysis. Corrected item-total correlations for the two subscales "communication in quiet situations" and "communication in adverse situations" were 0.47-0.81 and 0.58-0.80, respectively. The convergent validity of the questionnaires was adequate as reflected by a Spearman's coefficient of 0.67. CONCLUSION: Both questionnaires show good psychometric properties.

Targeted Next-Generation Sequencing of Cancer-Related Genes in a Norwegian Patient Cohort With Head and Neck Squamous Cell Carcinoma Reveals Novel Actionable Mutations and Correlations With Pathological Parameters.

BACKGROUND: Targeted next-generation sequencing (NGS) is increasingly applied in clinical oncology to advance personalized treatment. Despite success in many other tumour types, use of targeted NGS panels for assisting diagnosis and treatment of head and neck squamous cell carcinomas (HNSCC) is still limited. AIM: The focus of this study was to establish a robust NGS panel targeting most frequent cancer mutations in long-term preserved formalin-fixed paraffin-embedded (FFPE) tissue samples of HNSCC from routine diagnostics. MATERIALS AND METHODS: Tumour DNA obtained from archival FFPE tissue blocks of HNSCC patients treated at Haukeland University Hospital between 2003-2016 (n=111) was subjected to mutational analysis using a custom made AmpliSeq Library PLUS panel targeting 31 genes (Illumina). Associations between mutational burden and clinical and pathological parameters were investigated. Mutation and corresponding clinicopathological data from HNSCC were extracted for selected genes from the Cancer Genome Atlas (TCGA) and used for Chi-square and Kaplan-Meier analysis. RESULTS: The threshold for sufficient number of reads was attained in 104 (93.7%) cases. Although the specific number of PCR amplified reads detected decreased, the number of NGS-annotated mutations did not significantly change with increased tissue preservation time. In HPV-negative carcinomas, mutations were detected mainly in TP53 (73.3%), FAT1 (26.7%) and FLG (16.7%) whereas in HPV-positive, the common mutations were in FLG (24.3%) FAT1 (17%) and FGFR3 (14.6%) genes. Other less common pathogenic mutations, including well reported SNPs were reproducibly identified. Presence of at least one cancer-specific mutations was found to be positively associated with an extensive desmoplastic stroma (p=0.019), and an aggressive type of invasive front (p=0.035), and negatively associated with the degree of differentiation (p=0.041). Analysis of TCGA data corroborated the association between cancer-specific mutations and tumour differentiation and survival analysis showed that tumours with at least one mutation had shorter disease-free and overall survival (p=0.005). CONCLUSIONS: A custom made targeted NGS panel could reliably detect several specific mutations in archival samples of HNSCCs preserved up to 17 years. Using this method novel associations between mutational burden and clinical and pathological parameters were detected and actionable mutations in HPV-positive HNSCC were discovered.

Importance of personality and coping expectancy on patient-reported hearing disability, quality of life and distress level: a study of patients referred to an audiology service.

PURPOSE: According to the World Health Organization (WHO), hearing loss (HL) affects up to 15% of the world's adult population. Coping and personality are hypothesized to underlie quality of life (QoL) and distress scores. We aimed to study the importance of personality and coping in persons with HL for self-reported hearing disability, QoL, and distress. METHODS: A cross-sectional survey was carried out, including one hundred and fifty-eight adults seeking hearing aids. Pure-tone average hearing thresholds (PTA) were determined for each ear. A revised version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) served as a measure of self-reported hearing disability. Further, the generic part of the European Organization for Research and Treatment (EORTC) QoL questionnaire and the General Health Questionnaire (GHQ) (distress measure) were answered. Levels of neuroticism and the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) coping expectancy were determined. RESULTS: Hearing disability was determined by PTA (better ear) and level of neuroticism. Distress and QoL were determined by neuroticism and coping. CONCLUSION: More neuroticism was associated with worse outcome for the variables hearing disability, distress, and QoL. Helplessness and hopelessness were associated with worse hearing disability, increased distress, and lowered QoL. Patient reported hearing disability was also associated with PTA (better ear). There is a need to investigate further the associations between hearing disability and QoL to psychosocial parameters.

Long-Term Survival in 1,931 Patients With Dizziness: Disease- and Symptom-Specific Mortality.

OBJECTIVE: To evaluate mortality among patients referred for suspected vestibular disorder and to examine whether specific symptoms or disorders predict long-term survival among patients with dizziness or vertigo. STUDY DESIGN: Retrospective cohort study. METHODS: This retrospective cohort study analyzed long-term survival data. Consecutive patients examined for suspected vestibular disease at an otolaryngology clinic completed a detailed questionnaire regarding symptoms and comorbidities. RESULTS: The study included 1,931 patients. Their mean age (standard deviation) was 50.5 (16.5) years, and 60% were women. The mean follow-up period was 20.6 years (range, 15.3-27.5 years). The standardized mortality ratio for the entire cohort compared with the Norwegian age- and sex-matched population was 1.03 (95% confidence interval [CI]: 0.94-1.12), illustrating no difference in overall survival. Patients with a cerebrovascular cause of dizziness had higher mortality in adjusted Cox regression analyses (hazard ratio [HR] 1.56, 95% CI: 1.11-2.19), whereas patients reporting periodic or short attacks of dizziness had lower mortality (HR 0.62 [0.50-0.77] and 0.76 [0.63-0.93], respectively). Reported unsteadiness between dizziness attacks was associated with higher mortality with an HR of 1.30 (95% CI: 1.08-1.57). CONCLUSION: This long-term study found comparable mortality rates between patients evaluated for suspected vestibular disorder and that of the general population. However, subgroup analyses showed reduced mortality in patients with periodic or short attacks of dizziness and increased mortality in patients with unsteadiness between attacks or cerebrovascular causes of dizziness. The time course of vestibular symptoms should be determined, and thorough evaluation including fall risk and comorbidities must be considered in patients with nonepisodic symptoms. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2031-E2037, 2021.

Reduced grey- and white matter volumes due to unilateral hearing loss following treatment for vestibular schwannoma.

OBJECTIVE: Previous studies of the consequences of unilateral hearing loss (UHL) on the functional-structural organization of the brain has included subjects with various degrees of UHL. We suggest that the consequences of a total loss of hearing in one ear might differ from those seen in subjects with residual hearing in the affected ear. Thus, the main aim of the present study was to compare the structural properties of auditory and non-auditory brain regions in persons with complete UHL to those of normal hearing controls. We hypothesize that the consequences of complete UHL following treatment for vestibular schwannoma will differ between ipsi- and contralateral structures, as well as between right- and left side deafness. DESIGN: A 3T Siemens Prisma MR-scanner was used. Anatomical images were acquired using a high-resolution T1-weighted sequence. Grey- and white matter volumes were assessed using voxel-based morphometry. STUDY SAMPLE: Twenty-two patients with left- or right-side unilateral hearing loss. Fifty normal hearing controls. RESULTS: Reductions in grey- and white matter volumes were seen in cortical and sub-cortical regions, mainly in the right hemisphere including the auditory cortex, lingual gyrus, cuneus, middle temporal gyrus, occipital fusiform gyrus, middle cingulate gyrus and the superior temporal gyrus. Patients displayed reduced grey- and white matter volumes in cerebellar exterior structures ipsilateral to the tumor side. CONCLUSION: When compared to controls, right side hearing loss yields more widespread reduction of grey matter volume than left side hearing loss. The findings of reduced grey- and white matter volumes in auditory and non-auditory brain regions could be related to problems with speech perception in adverse listening conditions, increased listening effort and reduced quality of life reported by persons with unilateral hearing loss despite normal hearing in the unaffected ear.

The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles.

C-reactive protein (CRP) has a prognostic impact in head and neck squamous cell carcinoma (HNSCC). However, the acute phase reaction involves many other proteins depending on its inducing events, including various cytokines that can function as reaction inducers. In the present study, we compared the pretreatment acute phase cytokine profile for 144 patients with potentially curative HNSCC. We investigated the systemic levels of interleukin (IL)6 family mediators (glycoprotein (gp130), IL6 receptor (R)α, IL6, IL27, IL31, oncostatin M (OSM), ciliary neurotrophic factor (CNTF)), IL1 subfamily members (IL1R antagonist (A), IL33Rα), and tumor necrosis factor (TNF)α. Patient subsets identified from this 10-mediator profile did not differ with regard to disease stage, human papilloma virus (HPV) status, CRP levels, or death cause. Increased CRP, IL6, and IL1RA levels were independent markers for HNSCC-related death in the whole patient population. Furthermore, gp130, IL6Rα, and IL31 were suggested to predict prognosis among tumor HPV-negative patients. Only IL6 predicted survival in HPV-positive patients. Finally, we did a clustering analysis of HPV-negative patients based on six acute phase mediators that showed significant or borderline association with prognosis in Kaplan-Meier analyses; three subsets could then be identified, and they differed in survival (p < 0.001). To conclude, (i) HPV-negative and HPV-positive HNSCC patients show similar variations of their systemic acute phase profiles; (ii) the prognostic impact of single mediators differs between these two patient subsets; and (iii) for HPV-negative patients, acute phase profiling identifies three patient subsets that differ significantly in survival.

Evaluation of Self-reported Symptoms in 1,457 Dizzy Patients and Associations With Caloric Testing and Posturography.

OBJECTIVE: To determine if symptoms regarding timing and triggers of dizziness are useful for categorizing patients with dizziness, and to evaluate how patient-reported symptoms predict vestibular asymmetry, postural sway, and vestibular diagnoses. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients referred for suspected vestibular disease. INTERVENTIONS: Patients completed a symptom questionnaire before laboratory testing with static posturography and bithermal caloric tests. MAIN OUTCOME MEASURE: Evaluate whether responses from a symptom questionnaire predict caloric asymmetry, postural balance, and diagnoses. RESULTS: One thousand four hundred fifty seven patients, 60.1% women, mean age 49.9 (±16.6) years were included. Vomiting was the strongest predictor for caloric asymmetry in adjusted analysis, odds ratio (OR): 1.60 (95% confidence interval [CI]: 1.24-2.06), followed by chronic hearing loss OR: 1.59 (1.19-2.13). Patients who reported constant dizziness had impaired postural balance, quantified as 15% increase in postural sway in adjusted analyses (7.25-24.6%). We found no association between caloric asymmetry and postural instability with eyes closed. CONCLUSION: Most patients were able to describe the timing of their symptoms and a categorization based on timing seems feasible. There seemed to be an over-reporting of triggers and confirmatory testing of triggers is therefore advocated. Vomiting, but not nausea, was a strong indicator of vestibular disease in this primarily outpatient population. Caloric asymmetry and postural balance were not associated, and assessment of fall risk may be warranted in patients who reports constant dizziness, visual disturbances or dizziness triggered by light, darkness or sounds.

Acoustic Voice Analysis and Maximum Phonation Time in Relation to Voice Handicap Index Score and Larynx Disease.

OBJECTIVES: Patients with voice-related disorders are ideally treated by a multidisciplinary team. Acoustic voice analysis and patient-reported outcome measures are recommended parts of the clinical assessment. The present paper aims at further documenting the importance of acoustic voice analyses, maximum phonation time (MPT) and Voice Handicap Index (VHI) into clinical investigations. STUDY DESIGN: The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N = 23 dysfunctional, N = 75 degenerative/inflammation (N = 19 various excluded)) were included consecutively at the outpatient laryngology clinic at Haukeland University Hospital. In addition, a control group of 98 healthy subjects were included. METHOD: Voice samples, MPT, and the VHI scores in addition to standard clinical information were obtained. Acoustic analyses were performed from these samples determining level of jitter, shimmer and Noise-to-Harmonic ratio (NHR) as well as analyzing frequency of a prolonged vowel. RESULTS: Jitter, shimmer, and NHR scores correlated strongly (r ≈ 0.8; P < 0.001) to each other. By Analysis of Variance analyses, we have determined significant dependence on diagnostic group analyzing all the obtained acoustic scores (all P < 0.001). All patient groups but the dysfunctional group scored to some extent worse than the control group (mostly at P < 0.001). In addition, jitter scores from dysfunction group were lower than recurrent palsy group (P < 0.05) and shimmer scores were lower among dysfunctional than the cancer group (P < 0.05). Regarding NHR the cancer patients scored higher than the degenerative/inflammatory group (P < 0.05). The cancer group scored with longer MPT than the degenerative/inflammatory (P < 0.001) and recurrent palsy groups (P < 0.05). CONCLUSION: Among larynx disease patients acoustic and MPT analyses segregated with all determined analyses between patients and control conditions except the dysfunctional group, but also to some extent between various patient groups. VHI scores correlated to jitter, shimmer and NHR scores among cancer and degenerative/inflammatory disease patients. Acoustic analyses potentially add information useful to laryngological patient studies.

EORTC Quality of Life Questionnaire Head and Neck (H&N)-35 scores from H&N squamous cell carcinoma patients obtained at diagnosis and at 6, 9 and 12 months following diagnosis predict 10-year overall survival.

PURPOSE: To study the 10-year overall survival predictions, and mechanisms behind, of head and neck (HN) quality of life (QoL) scores obtained at diagnosis and 6, 9, and 12 months following diagnosis in a cohort of HN squamous cell carcinoma (HNSCC) patients. METHODS: Consecutive HNSCC patients (N = 109) subjected to standard workup and treatment self-reported their QoL measured by the EORTC Quality of Life Questionnaire (QLQ) H&N-35 between November 2002 and June 2005. Each QoL index was calculated and additionally aggregated to one sum score. The included patients were at diagnosis younger than 78 years, judged adequately cognitive functioning, and scheduled for curative treatment. Self-reported smoking, alcohol consumption, and socio-demographic information were registered. Twenty-two patients were high-risk (hr)-HPV DNA tumor positive. If the treatment goal was changed to palliative, no new QoL information was collected. All living patients were followed until 10 years after diagnosis. RESULTS: Median survival was 105 months. Significant overall survival predictions were found from the EORTC H&N-35 QLQ sum scores continuously measured at diagnosis (p = 0.006) and obtained at 6 (p = 0.02), 9 (p = 0.002) and 12 (p = 0.05) months. Lower QoL predicted lower overall survival. These sum score survival predictions were in part independent of TNM stage, hr-HPV status, gender, age, alcohol and smoking status. The indices "pain", "swallowing", "social eating", and "feeling ill" were predictive of survival at 3 out of 4 measuring points (diagnosis, 6, 9 and 12 months) in univariate analyses. CONCLUSION: EORTC H&N-35 QLQ scores at diagnosis and throughout the first year thereafter harbor prognostic power.

An fMRI-study on single-sided deafness: Spectral-temporal properties and side of stimulation modulates hemispheric dominance.

OBJECTIVE: Our main aim was to investigate the blood oxygenation level dependent (BOLD) response to monaural and binaural speech- and non-speech stimuli as measured with fMRI in subjects with single-sided deafness and in normal hearing controls. We hypothesised that the response to monaural stimulation in both normal hearing subjects and persons with single-sided deafness would vary with the complexity and nature of the stimuli and the side of stimulation. DESIGN: Patients with left- and right single-sided deafness and controls with normal hearing receiving either binaural or monaural stimuli were tested using speech and non-speech auditory stimuli in an event-related fMRI experiment. STUDY SAMPLE: Twenty-two patients with single-sided deafness after treatment for vestibular schwannoma and 50 normal hearing controls. RESULTS: Normal hearing persons receiving right side monaural stimuli activate bilateral temporal regions. Activation following left side monaural stimulation is more right lateralized. Persons with single-sided deafness respond similarly to controls to monaural stimulation. Persons with right side single-sided deafness show activation of frontal cortical regions not seen in persons with left side single-sided deafness following speech stimuli. This is possibly related to increased effort and more frequently reported problems with communication. Right side single-sided deafness is related to increased activation of areas usually related to processing of degraded input, including the thalamus. CONCLUSION: Hemispheric dominance following monaural auditory stimulation is modulated by the spectral-temporal properties of the stimuli and by which ear is stimulated. Differences between patients with right- and left side deafness suggests that right side deafness is related to increased activation of areas involved in processing of degraded input.

Quality of life in persons with hearing loss: a study of patients referred to an audiological service.

Objective: To investigate the relationship between hearing loss (HL) and general quality of life (QoL) in adults seeking hearing aids (HAs). Design: The patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire's general part and a questionnaire measuring self-assessed communication ability (Abbreviated Profile of hearing Aid Benefit-APHAB). These responses were compared with EORTC scores from a general population and patients with former head and neck cancer. Study sample: One-hundred and fifty-eight adults with HL were recruited prior to hearing aid (HA) fitting with one half seeking renewal of their HA. Results: General QoL scores among patients with HL were similar to those in the general population, but higher than in many chronic serious diseases. Patients with unilateral HL reported slightly worse social function and more fatigue than patients with bilateral HL. Self-assessed communication ability correlated with general QoL scores. Also, we found that best ear pure tone average (PTA), cognitive and physical QoL function predicted APHAB scores. Conclusion: In the investigated HL group, general QoL scores seem to be relatively close to those seen in the general population.

Hearing as an Independent Predictor of Postural Balance in 1075 Patients Evaluated for Dizziness.

OBJECTIVE: To evaluate the association between hearing and postural balance. STUDY DESIGN: Retrospective cross-sectional study. SETTING: Tertiary care otolaryngology clinic. SUBJECTS AND METHODS: Patients examined for suspected vestibular disorder were included in this study. The outcome variable was postural sway measured by static posturography during quiet standing with eyes closed. The predictor variable was pure-tone average hearing threshold on the best hearing ear at 0.5, 1, 2, and 3 kHz. Covariates were age, sex, and vestibular disease or vestibular asymmetry assessed by bithermal caloric irrigation. RESULTS: In total, 1075 patients were included. Increased hearing threshold was a strong predictor of increased postural sway (path length) after correcting for age and sex. A 10-dB increase in hearing loss on the best hearing ear predicted a mean 6.0% increase in path length (confidence interval, 2.9%-9.3%, P < .001). Of the covariates, increasing age (P < .001) and male sex (P = .009) were significant predictors of increased postural sway. The effect of increased hearing threshold was also significant after adjusting for vestibular disease. CONCLUSION: Increased hearing threshold was an independent predictor of increased postural instability, and this effect was strongest for the best hearing ear. Unilateral vestibular disease did not seem to explain this association between hearing and postural balance. Reduced hearing is associated with impaired balance, and interventions to prevent falls should be considered for patients at risk.

Periodontal status at diagnosis predicts non-disease-specific survival in a geographically defined cohort of patients with oropharynx squamous cell carcinoma.

BACKGROUND: The aim of this study was to examine periodontal status with a time-efficient screening method from a cohort of newly diagnosed oropharynx squamous cell carcinoma (OPSCC) patients and to study to what extent dental disease level predicted survival. Aims/objective: Can measuring level of dental pathology based on a blind investigation of a routine orthopantogram (OPG) obtained during diagnostic workup reveal prognostic information? MATERIALS AND METHODS: We included 97 patients diagnosed between 2003 and 2010. Radiographic alveolar bone loss was measured. At least 4 mm bone loss from cement-enamel junction on at least two teeth was registered as periodontal pathology. The number of missing and filled teeth (MFT), residual roots and apical radiolucencies were noted. Clinical data were determined through hospital patient records. RESULTS: The horizontal bone loss discriminated between hr-HPV(+) versus hr-HPV(-) status, but secondary to age and smoking history at diagnosis. Vertical and horizontal bone loss predicted survival directly, and adjusted by gender, patient, smoking history, TN stage and hr-HPV tumor infection at diagnosis. CONCLUSIONS: Degree of periodontal OPG pathology at the time of OPSCC diagnosis to some extent predicted hr-HPV infection, but predicted non-disease-specific long-term survival. SIGNIFICANCE: Degree of periodontal OPG pathology at diagnosis predicts prognosis.

Generic quality of life in persons with hearing loss: a systematic literature review.

BACKGROUND: To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL. METHODS: Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria. RESULTS: Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL. CONCLUSIONS: The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.