The Rhinoplasty Health Care Monitor: An Update on the Practical and Clinical Benefits after 10 Years of Prospective Outcome Measurements.

The era of value-based health care is characterized by an increasing interest in patient-reported health outcomes. For this purpose we developed the rhinoplasty health care monitor (RHM), a streamlined outcome measurement protocol, including all rhinoplasty patients since 2014. Statistical analyses of patient-reported outcome data are automated and visually presented on a custom web-based dashboard. We describe the clinical and practical benefits of the RHM and discuss how routine prospective outcome measurements have upgraded our care standards. For this prospective study, 979 consecutive patients referred for functional (revision) rhinoplasty from April 2014 to August 2023 were included. Preoperative and 3- and 12-month postoperative scores on the Nasal Obstruction Symptom Evaluation scale (NOSE), Utrecht Questionnaire (UQ), and visual analog scales (VAS) were obtained. Of 979 referred patients, 599 (61.2%) were eligible for rhinoplasty. One year postoperatively, mean NOSE scale sum score improved from 69.1 ± 22.8 to 23.1 ± 23.5 (p < 0.001). Functional VAS scores improved from 4.1 ± 2.8 (left) and 4.1 ± 2.8 (right) to 7.5 ± 1.9 (left) and 7.3 ± 2.0 (right; p < 0.001). Mean UQ sum score improved from 12.0 ± 6.4 to 6.8 ± 3.3 and aesthetic VAS score improved from 4.5 ± 2.5 to 7.4 ± 1.7 (p < 0.001) 1 year postoperatively. Benefits of the outcome routine were improved patient selection, data-driven expectation management and patient empowerment, and targeted critical appraisals of surgical performance. In conclusion, routine, automated, prospective outcome monitoring provides physicians with a response to the increasing demand for data-driven insights in health outcomes. The limited effort that is needed to gather and monitor outcome data is heavily repaid by valuable insights into aspects of care that can be improved.

Multi-Domain Screening: Identification of Patient's Risk Profile Prior to Head-and-Neck Cancer Treatment.

BACKGROUND: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patients' age, performance status, and cancer group staging. METHODS: Patients (N = 128) underwent multi-domain screening consisting of the Eating Assessment Tool-10 for OD, Short Nutritional Assessment Questionnaire and BMI for malnutrition, Short Physical Performance Battery and Hand Grip Strength for sarcopenia, and Distress Thermometer and Maastricht Frailty Screening Tool for frailty. RESULTS: 26.2%, 31.0%, 73.0%, and 46.4% of the patients were at risk for OD, malnutrition, sarcopenia, or frailty, respectively. Patients with an advanced cancer stage had a significantly higher risk of OD and high levels of distress prior to cancer treatment. CONCLUSIONS: This study identified the risk profile of newly diagnosed HNC patients using a standardized 'quick and easy' multi-domain screening prior to cancer treatment.

Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions.

Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/− 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%). Results: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%). Conclusions: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

Evaluation of the Sensitivity of Metabolic Profiling by Rapid Evaporative Ionization Mass Spectrometry: Toward More Radical Oral Cavity Cancer Resections.

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivo metabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivo by REIMS during four glossectomies. Complementary desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivo REIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivo tissue recognition during oral cavity cancer surgeries.

Additional parameters to improve the prognostic value of the 8th edition of the UICC classification for human papillomavirus-related oropharyngeal tumors.

BACKGROUND: The prognostic reliability of the UICC's TNM classification (8th edition) for human papillomavirus (HPV)-positive tonsillar squamous cell carcinomas (TSCCs) compared to the 7th edition was explored, and its improvement by using additional anatomical and nonanatomical parameters. METHODS: One hundred and ten HPV-positive and 225 HPV-negative TSCCs were retrospectively analyzed. Survival was correlated with patient and tumor characteristics (7th and 8th edition UICC TNM classification). RESULTS: In HPV-positive TSCCs, the 8th edition UICC's TNM classification correlated better with prognosis than the 7th edition. Also, smoking status was a stronger prognosticator of survival than UICC staging. Non- or former smokers had a 5-year overall survival of 95.1% regardless of tumor stage. Furthermore, age (>65 years), cN3, and M1 classification were significant prognostic factors. CONCLUSION: The prognostic value of the 8th edition UICC's TNM classification improved significantly when compared to the 7th edition. Nonetheless, further improvement is possible by adding nonanatomical factors (smoking, age >65 year) and separating N0-N2 from N3.

Awareness of HPV-associated oropharyngeal cancers among GPs in The Netherlands: a cross-sectional study.

BACKGROUND: The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) is increasing in high income countries. HPV-associated OPC generally presents as an invasive disease, often with lymph node involvement, in relatively young patients with minimal or no history of smoking and alcohol consumption. Knowledge on HPV-associated OPC among primary care professionals is essential for disease recognition and early start of treatment. AIM: To examine the knowledge on HPV-associated OPC among GPs in the Netherlands. DESIGN & SETTING: A cross-sectional postal survey among GPs in the Netherlands. METHOD: A 12-item questionnaire was sent to 900 randomly selected general practices. Outcome measures included awareness of the link between HPV and OPC, epidemiological trends, and patient characteristics. Data were statistically analysed for sex, years after graduation, and self-rated knowledge of OPC. RESULTS: A total of 207 GPs participated in this study. Seventy-two per cent recognised HPV as a risk factor for OPC and 76.3% were aware of the increasing incidence rate of HPV-associated OPC. In contrast, 35.7% of participants knew that patients with HPV-associated OPC are more often male, and just over half (53.6%) of the participants were aware of the younger age of these patients. CONCLUSION: More than one-quarter of GPs in the Netherlands are unaware of HPV as a causative factor for OPC. Furthermore, there is a gap in knowledge on characteristics of patients with HPV-associated OPC . Further training on these topics could improve disease recognition and, ultimately, patient survival.

Upfront Surgery vs. Primary Chemoradiation in an Unselected, Bicentric Patient Cohort with Oropharyngeal Squamous Cell Carcinoma-A Matched-Pair Analysis.

The two pillars of therapy for oropharyngeal squamous cell carcinoma (OPSCC) are upfront surgery and primary chemoradiotherapy. Substantial regional preferences exist with regard to the selection of treatment. Despite new therapeutic approaches, patient survival remains poor, with an approximate overall survival (OS) rate of 50% at five years. This study was conducted to investigate a potential survival benefit depending on the treatment modality in OPSCC patients. We retrospectively collected data of 853 patients with histologically confirmed OPSCC from the Giessen and Maastricht cancer databases. To identify risk factors affecting survival, a Cox-proportional hazard model was applied to 442 patients with complete data sets. Based on this cohort a matched-pair analysis with 158 patients was performed to compare OS rates of patients treated either with upfront surgery or primary chemoradiation. For the collective cohort, patients treated with upfront surgery had significantly improved OS rates compared to patients treated with primary chemoradiation. In the matched-pair analysis adjusted for patients' T-, N- and HPV-status as well as risk profile, we observed that both treatment approaches offered equivalent OS rates. Our study emphasizes that treatment recommendations should be made whenever possible on the basis of side-effect profiles caused by the therapeutic approach used. To draw further conclusions, results of the ongoing "best of" (NCT2984410) study are eagerly awaited, investigating the functional outcome after treatment of OPSCC patients.

Causes and Consequences of HPV Integration in Head and Neck Squamous Cell Carcinomas: State of the Art.

A constantly increasing incidence in high-risk Human Papillomaviruses (HPV)s driven head and neck squamous cell carcinomas (HNSCC)s, especially of oropharyngeal origin, is being observed. During persistent infections, viral DNA integration into the host genome may occur. Studies are examining if the physical status of the virus (episomal vs. integration) affects carcinogenesis and eventually has further-reaching consequences on disease progression and outcome. Here, we review the literature of the most recent five years focusing on the impact of HPV integration in HNSCCs, covering aspects of detection techniques used (from PCR up to NGS approaches), integration loci identified, and associations with genomic and clinical data. The consequences of HPV integration in the human genome, including the methylation status and deregulation of genes involved in cell signaling pathways, immune evasion, and response to therapy, are also summarized.

Public awareness of the association between human papillomavirus and oropharyngeal cancer.

BACKGROUND: Early diagnosis of human papillomavirus (HPV) associated oropharyngeal cancer (OPC) is associated with improved survival. To achieve early diagnosis, it might be beneficial to increase awareness of the link between HPV and OPC. This increase of awareness could also be an important way to increase vaccination rates. The aim of our study was to explore the current public knowledge in the Netherlands regarding the association of HPV with OPC. METHODS: An online cross-sectional survey was used and sent by the company Flycatcher Internet Research to 1539 of their panel members. Data were analyzed statistically by gender, age, educational level and the participants' use of alcohol and tobacco. RESULTS: The response rate was 68% (1044 participants). Our data revealed that 30.6% of the participants had heard of HPV. There was a knowledge gap regarding HPV in males (P < 0.001), people older than 65 years (P < 0.001), people with low education level (P < 0.001) and current smokers (P < 0.001). Of the respondents who had heard of HPV, only 29.2% knew of the association between HPV and OPC. We also found that only 49.7% of the population knew of the existence of an HPV vaccine. CONCLUSIONS: The results of this survey indicate that the public awareness of HPV and the association of HPV with OPC is lacking. Interventions to increase awareness of HPV and its association with non-cervical cancer should be considered. This might help to increase the HPV vaccine uptake both for girls and boys and earlier diagnosis of this disease leading to improved survival.

Evaluating the safety of oral methylene blue during swallowing assessment: a systematic review.

OBJECTIVE: Methylene blue (MB) is frequently administered during fiberoptic endoscopic evaluation of swallowing (FEES) to enhance visualization of pharyngeal bolus transit. However, the safety of MB is being questioned since serious adverse events (AEs) such as hemodynamic instability, hemolysis, and serotonin syndrome were reported. The aim of this study is a systematic analysis of the literature to obtain an evidence-based overview of AEs due to oral administration of MB and to determine its safety as a food dye during swallowing assessment. METHODS: A systematic literature search was carried out in PubMed, Embase, and Cochrane Library. Two reviewers independently selected articles describing oral administration of MB as a main diagnostic/therapeutic intervention, dosage, and AEs. Expert opinions, conference papers, sample size < 10, and animal studies were excluded. Level of evidence of the included studies was determined. RESULTS: A total of 2264 unduplicated articles were obtained. Seventeen studies met the inclusion criteria with 100% agreement between the two reviewers. Among these, twelve studies were randomized controlled trials. In a pooled population of 1902 patients receiving oral MB, three serious AEs were reported related to MB. Non-serious AEs showed a dose-related trend and were usually mild and self-limiting. A meta-analysis could not be performed as studies were methodologically too heterogeneous. CONCLUSION: Serious AEs due to oral administration of MB are rare (n = 3, 0.16%). MB-related non-serious AEs are mild, self-limiting, and show a dose-related trend. These findings indicate that it is safe to use small amounts of MB as a food dye during swallowing examinations.

EAT-10 Scores and Fiberoptic Endoscopic Evaluation of Swallowing in Head and Neck Cancer Patients.

OBJECTIVE: The purpose of this study was to determine the relationship between patient-reported symptoms of oropharyngeal dysphagia (OD) using the Eating Assessment Tool (EAT)-10 and the swallowing function using a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol in head and neck cancer (HNC) patients with confirmed OD. METHODS: Fifty-seven dysphagic HNC patients completed the EAT-10 and a FEES. Two blinded clinicians scored the randomized FEES examinations. Exclusion criteria consisted of presenting with a concurrent neurological disease, scoring below 23 on a Mini-Mental State Examination, being older than 85 years, having undergone a total laryngectomy, and being illiterate or blind. Descriptive statistics, linear regression, sensitivity, specificity, and predictive values were calculated. RESULTS: The majority of the dysphagic patients (N = 38; 66.7%) aspirated after swallowing thin liquid consistency. A large number of patients showed postswallow pharyngeal residue while swallowing thick liquid consistency. More specifically, 42 (73.0%) patients presented postswallow vallecular residue, and 39 (67.9%) patients presented postswallow pyriform sinus residue. All dysphagic patients had an EAT-10 score ≥ 3. Linear regression analyses showed significant differences in mean EAT-10 scores between the dichotomized categories (abnormal vs. normal) of postswallow vallecular (P = .037) and pyriform sinus residue (P = .013). No statistically significant difference in mean EAT-10 scores between the dichotomized categories of penetration or aspiration was found (P = .966). CONCLUSION: The EAT-10 questionnaire seems to have an indicative value for the presence of postswallow pharyngeal residue in dysphagic HNC patients, and a value of 19 points turned out to be useful as a cutoff point for the presence of pharyngeal residue in this study population. LEVEL OF EVIDENCE: 2B.

Evidence for different molecular parameters in head and neck squamous cell carcinoma of nonsmokers and nondrinkers: Systematic review and meta-analysis on HPV, p16, and TP53.

BACKGROUND: The goal of this review was to present an overview of the currently identified molecular parameters in head and neck squamous cell carcinoma (HNSCC) of nonsmokers and nondrinkers (NSND). METHODS: Following the PRISMA guidelines, a systematic search was performed using the electronic databases PubMed, Embase, and Google Scholar. RESULTS: Of the 902 analyzed unique studies, 74 were included in a quantitative synthesis and 24 in a meta-analysis. Human papillomavirus (HPV) was reported as a molecular parameter in 38 studies, followed by p16 and TP53 (23 and 14 studies, respectively). The variety of other molecular parameters concerned sporadic findings in small numbers of NSND. CONCLUSIONS: HNSCC in NSND is more often related to HPV and p16 overexpression compared to tumors of smokers-drinkers. In a third of virus-negative tumors, TP53 mutations were detected with a mutational profile associated with aging and ultraviolet light exposure rather than to tobacco consumption.

Patients with Head-and-Neck Cancer: Dysphagia and Affective Symptoms.

OBJECTIVE: Affective symptoms are common in patients with head-and-neck cancer. This study determined the association between the presence of aspiration and symptoms of anxiety and depression, as well as patient characteristics in patients with head-and-neck cancer and dysphagia. METHODS: Eighty-four patients with head-and-neck cancer and dysphagia completed the Hospital Anxiety and Depression Scale and underwent a standardized fiberoptic endoscopic evaluation of swallowing. Linear regression analysis was performed to explore the associations. RESULTS: Fifty-two (61.9%) patients presented clinically relevant symptoms of anxiety or depression. Forty-eight (57.1%) patients presented with aspiration during fiberoptic endoscopic evaluation of swallowing. A significant negative association was found between the presence of aspiration and affective (anxiety and depression) symptoms (p = 0.04). Male patients presented significantly lower symptom scores of anxiety compared to females (p = 0.04). CONCLUSIONS: Clinically relevant affective symptoms were present in more than half of all patients with head-and-neck cancer and dysphagia. Surprisingly, a significant negative association was found between the presence of aspiration and these affective symptoms. Gender was also significantly associated with affective symptoms. These results suggest that there is a need for further investigation into the impact of psychological distress on patients with head-and-neck cancer and dysphagia.

Stromal vapors for real-time molecular guidance of breast-conserving surgery.

Achieving radical tumor resection while preserving disease-free tissue during breast-conserving surgery (BCS) remains a challenge. Here, mass spectrometry technologies were used to discriminate stromal tissues reported to be altered surrounding breast tumors, and build tissue classifiers ex vivo. Additionally, we employed the approach for in vivo and real-time classification of breast pathology based on electrosurgical vapors. Breast-resected samples were obtained from patients undergoing surgery at MUMC+. The specimens were subsequently sampled ex vivo to generate electrosurgical vapors analyzed by rapid evaporative ionization mass spectrometry (REIMS). Tissues were processed for histopathology to assign tissue components to the mass spectral profiles. We collected a total of 689 ex vivo REIMS profiles from 72 patients which were analyzed using multivariate statistical analysis (principal component analysis-linear discriminant analysis). These profiles were classified as adipose, stromal and tumor tissues with 92.3% accuracy with a leave-one patient-out cross-validation. Tissue recognition using this ex vivo-built REIMS classification model was subsequently tested in vivo on electrosurgical vapors. Stromal and adipose tissues were classified during one BCS. Complementary ex vivo analyses were performed by REIMS and by desorption electrospray ionization mass spectrometry (DESI-MS) to study the potential of breast stroma to guide BCS. Tumor border stroma (TBS) and remote tumor stroma (RTS) were classified by REIMS and DESI-MS with 86.4% and 87.8% accuracy, respectively. We demonstrate the potential of stromal molecular alterations surrounding breast tumors to guide BCS in real-time using REIMS analysis of electrosurgical vapors.

Ex Vivo Culture Models to Indicate Therapy Response in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is characterized by a poor 5 year survival and varying response rates to both standard-of-care and new treatments. Despite advances in medicine and treatment methods, mortality rates have hardly decreased in recent decades. Reliable patient-derived tumor models offer the chance to predict therapy response in a personalized setting, thereby improving treatment efficacy by identifying the most appropriate treatment regimen for each patient. Furthermore, ex vivo tumor models enable testing of novel therapies before introduction in clinical practice. A literature search was performed to identify relevant literature describing three-dimensional ex vivo culture models of HNSCC to examine sensitivity to chemotherapy, radiotherapy, immunotherapy and targeted therapy. We provide a comprehensive overview of the currently used three-dimensional ex vivo culture models for HNSCC with their advantages and limitations, including culture success percentage and comparison to the original tumor. Furthermore, we evaluate the potential of these models to predict patient therapy response.

Detecting head and neck squamous carcinoma using a portable handheld electronic nose.

INTRODUCTION: Detecting volatile organic compounds in exhaled breath enables the diagnosis of cancer. We investigated whether a handheld version of an electronic nose is able to discriminate between patients with head and neck squamous cell cancer (HNSCC) and healthy controls. METHODS: Ninety-one patients with HNSCC and 72 controls exhaled through an e-nose. An artificial neural network based model was built to separate between HNSCC patients and healthy controls. Additionally, three models were created for separating between the oral, oropharyngeal, and glottic subsites respectively, and healthy controls. RESULTS: The results showed a diagnostic accuracy of 72% at a sensitivity of 79%, specificity of 63%, and area under the curve (AUC) of 0.75. Results for the subsites showed an AUC of 0.85, 0.82, and 0.83 respectively for oral, oropharyngeal, and glottic HNSCC. CONCLUSION: This feasibility study showed that this portable noninvasive diagnostic tool can differentiate between HNSCC patients and healthy controls.

Swallow-related quality of life and oropharyngeal dysphagia in myotonic dystrophy.

PURPOSE: This study describes swallow-related quality of life (SWAL-QOL) in patients with myotonic dystrophy type 1 (DM1) and investigates its association with swallowing function and disease severity. METHODS: A SWAL-QOL questionnaire was completed by 75 DM1 patients and 25 healthy control subjects. The severity of the disease was evaluated using the muscular impairment rating scale (MIRS). Twenty-eight DM1 patients underwent a videofluroscopic swallowing examination (VFS). Spearman's correlation coefficient was used to measure the direction and strength of associations. RESULTS: The SWAL-QOL median scores were significantly lower for the DM1 group than for the healthy control group. The scores for the majority of the SWAL-QOL domains were lower in patients with proximal muscular weakness (MIRS 4 and 5). Postswallow vallecular pooling and piecemeal deglutition were the most impaired VFS outcome variables. CONCLUSION: Our results suggest that a multidimensional swallowing assessment is recommended for DM1 patients as SWAL-QOL and VFS measure different aspects of the swallowing function, thus providing complementary information.

Tumor control of cervical lymph node metastases of unknown primary origin: the impact of the radiotherapy target volume.

PURPOSE: Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral centers, the post-surgical radiation target volume changed from the bilateral neck including the pharyngeal axis to the unilateral neck only, in the course of the last decade. This study aims to investigate the outcome of patients with CUP before and after de-escalation of post-surgical radiotherapy. METHODS: Data of two Dutch tertiary referral centers were merged. Disease-free survival (DFS), overall survival (OS), and regional control rate (RCR) of 80 patients diagnosed with CUP (squamous cell and undifferentiated carcinomas) between 1990 and 2009 were retrospectively analyzed. RESULTS: Thirty patients received bilateral neck and pharyngeal axis radiotherapy and 42 patients ipsilateral radiotherapy only. In another eight patients, the postsurgical radiation target volume was expanded to the contralateral neck or to the pharyngeal axis, due to suspicious lesions on imaging. The 5-year DFS, OS and RCR were 60%, 51.2%, and 80%, respectively, in the total patient population. RCR did not differ in patients treated with ipsilateral as compared to bilateral radiotherapy nor did 5-year OS and DFS. No tumors occurred in the pharyngeal axis. CONCLUSION: In this study, omitting elective treatment of the contralateral neck and pharyngeal axis did not lead to a decrease in locoregional control or survival rates when treating patients with CUP.

Presence of Human Papillomavirus and Epstein-Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers.

OBJECTIVE: Determine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND). METHODS: Clinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis. RESULTS: All oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression. CONCLUSION: In this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.

Association Between Pharyngeal Pooling and Aspiration Using Fiberoptic Endoscopic Evaluation of Swallowing in Head and Neck Cancer Patients with Dysphagia.

Postswallow pharyngeal pooling may be a risk factor for tracheal aspiration. However, limited literature shows the potential association between pharyngeal pooling and aspiration in head and neck cancer (HNC) patients. This study investigates the relationship between postswallow pharyngeal pooling and aspiration in HNC patients with oropharyngeal dysphagia. Furthermore, the effects of tumor stage, tumor location, and cancer treatment on aspiration were examined. Ninety dysphagic HNC patients underwent a standardized fiberoptic endoscopic evaluation of swallowing (FEES) using thin and thick liquid boluses. For each swallow, three visuoperceptual ordinal variables were scored: postswallow vallecular pooling, postswallow pyriform sinus pooling, and aspiration. Logistic regression analyses with correction for the location of pooling, tumor stage, tumor location, and cancer treatment were performed to explore the association between pooling and aspiration. No significant association was found between postswallow vallecular pooling and aspiration for thin liquid. However, severe versus mild-to-moderate postswallow vallecular pooling of thick liquid was significantly associated to aspiration. Similar results were seen after correction for the presence of pyriform sinus pooling, tumor stage, tumor location, or type of cancer treatment. This study showed a significant association between severe postswallow pyriform sinus pooling of thick liquid and aspiration, independent of the presence of vallecular pooling, tumor stage, tumor location, or cancer treatment. Concluding, location (valleculae versus pyriform sinuses), liquid bolus consistency (thin versus thick liquid), and amount of postswallow pharyngeal pooling (no pooling, mild/moderate pooling, severe pooling) have an influence on the probability of aspiration in dysphagic HNC patients, and they should be carefully considered during FEES, even in the absence of aspiration during the examination.