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Purpose This study aimed to evaluate the course of olfactory dysfunction [OD] due to upper respiratory tract infections [URTI] especially for COVID-19 [C19] in a multicentric design and to investigate possible predictors for the outcome. Methods In a multicentric study, patients (n = 147, of which 96 were women) with OD due to URTI, including C19 and non-C19 were evaluated at two visits with a standardized medical history and “Sniffin’ Sticks” extended psychophysical testing to examine the course and possible predictors for improvement of olfactory function. Results C19 patients showed better overall olfactory function (p p p = 0.20) except for a more pronounced improvement of odour threshold (p = 0.03) in C19. C19 patients with parosmia exhibited a higher probability of clinically relevant improvement of odour threshold, a better threshold in the second visit, and tended to have a better TDI-score at the second visit. Further possible predictors for an improving olfactory function were younger age, female gender, and had lower scores in olfactory tests at the first visit. Conclusions Patients with C19 and non-C19 URTI exhibit a similar improvement over 3–4 months except for the odour threshold, with a better TDI in both visits for C19. For C19 a better prognosis in terms of olfactory recovery was found for younger patients with parosmia and lower olfactory scores at the first visit. Still, for many patients with olfactory loss, an improvement that is experienced as complete may only occur over months and possibly years.

Overall survival by HPV-status. Overall survival stratified by HPV-status based on A) molecular HPV-status, B) seropositivity to HPV-16 E6, C) seropositivity to any high-risk HPV-types and D) by molecular HPV-status if available and seropositivity to any high-risk HPV-types if molecular HPV-status was unavailable. Overall survival was significantly longer regardless of the definition of HPV-status (p

Patient characteristics (non-oropharyngeal patients)

Prognostic impact of antibody responses to cancer antigens stratified by HPV-status. Overall survival was significantly shorter for patients with {greater than or equal to}2 AR, AR to c-myc, MAGåE-A1, MAGE-A4 and Rhodopsin E2 in the HPV-negative cohort and IMP-1 in the HPV-positive cohort. Overall survival was calculated using the Kaplan-Meier method and p-values were determined using logrank tests. Results were corrected for multiple testing with a false discovery rate of 15%.

Purpose:The identification of high-risk patients within human papillomavirus (HPV)-positive and -negative head and neck squamous cell carcinoma (HNSCC) is needed for improved treatment and surveillance strategies. In this study, we set out to discover antibody responses (AR) with prognostic impact in HNSCC stratified by HPV status.Experimental Design:A fluorescent bead–based multiplex serology assay on 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens, and 8 oncogenes) and 29 HPV antigens was performed in samples of 362 patients with HNSCC from five independent cohorts (153 HPV positive, 209 HPV negative). A multivariable Cox proportional hazard model with bootstrapping (M = 1000) was used for validation of prognostic antibody responses.Results:Antibody response to any of the cancer antigens was found in 257 of 362 patients (71%). In HPV-negative patients, antibody responses to c-myc, MAGE-A1, -A4, and Rhodopsin E2 (combined as ARhigh risk) were significantly associated with shorter overall survival. In HPV-positive patients, antibody responses to IMP-1 were discovered as a negative prognostic factor. ARhigh risk (HR = 1.76) and antibody responses to IMP-1 (HR = 3.28) were confirmed as independent markers for a poor prognosis in a multivariable Cox proportional hazard model with bootstrapping (M = 1000).Conclusions:We identified antibody responses to cancer antigens that associate with a dismal prognosis in patients with HNSCC beyond HPV-positive status. ARhigh risk may be used to detect HPV-negative patients with an extraordinarily bad prognosis. Most importantly, antibody response to IMP-1 may serve as a marker for a subgroup of HPV-positive patients who present with a poor prognosis similar to that in HPV-negative patients.

Consort diagram of the study cohort.

The COVID-19 pandemic brought attention to our limited understanding of human olfactory physiology. While the cellular composition of the human olfactory epithelium is similar to that of other vertebrates, its functional properties are largely unknown. We prepared acute slices of human olfactory epithelium from nasal biopsies and used the whole-cell patch-clamp technique to record electrical properties of cells. We measured voltage-gated currents in human olfactory sensory neurons and supporting cells, and action potentials in neurons. Additionally, inward currents and action potentials responses of neurons to a phosphodiesterase inhibitor indicated that the transduction cascade involves cAMP as a second messenger. Furthermore, responses to odorant mixtures demonstrated that the transduction cascade was intact in this preparation. This study provides the first electrophysiological characterization of olfactory sensory neurons in acute slices of the human olfactory epithelium, paving the way for future research to expand our knowledge of human olfactory physiology.

Lymph node status of the neck is the most important prognostic factor in head and neck cancer. Neck dissection, which consists of the systematic excision of the neck nodes, represents the gold standard of surgical treatment in clinically positive necks. In cases in which metastases to lymph nodes of the neck are not detectable, the decision to perform an elective neck dissection depends on the stage and the site of the primary tumor. This narrative review focuses on the anatomical description and oncological role of a group of lymph nodes of the neck that historically has not been well defined. Over the years, several authors have described the groups of lymph nodes that lie where the facial vein crosses the mandible, but to date, no unique definition or a clear view of their oncological role has been proposed. Recently, the term “perimarginal nodes” was coined to refer to this group of lymph nodes, and emphasis was placed on the risk of leaving them undissected during neck dissection. This paper aims to provide a surgical-anatomical classification of these lymph nodes and describe their oncological role on the basis of a review of the relevant literature.

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

Purpose Primary: To determine the rate of occult cervical metastases in primary temporal bone squamous cell carcinomas (TBSSC). Secondary: to perform a subgroup meta-analysis of the risk of occult metastases based on the clinical stage of the tumour and its risk based on corresponding levels of the neck. Methods A systematic review and meta-analysis of papers searched through Medline, Cochrane, Embase, Scopus and Web of Science up to November 2021 to determine the pooled rate of occult lymph node/parotid metastases. Quality assessment of the included studies was assessed through the Newcastle–Ottawa scale. Results Overall, 13 out of 3301 screened studies met the inclusion criteria, for a total of 1120 patients of which 550 had TBSCC. Out of the 267 patients who underwent a neck dissection, 33 had positive lymph nodes giving a pooled rate of occult metastases of 14% (95% CI 10–19%). Occult metastases rate varied according to Modified Pittsburg staging system, being 0% (0–16%) among 12 pT1, 7% (2–20%) among 43 pT2 cases, 21% (11–38%) among 45 pT3, and 18% (11–27%) among 102 pT4 cases. Data available showed that most of the positive nodes were in Level II. Conclusion The rate of occult cervical metastases in TBSCC increases with pathological T category with majority of nodal disease found in level II of the neck.

Objective: Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion: In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence: III

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BACKGROUND: This systematic review and meta-analysis aims to estimate the prevalence and prognostic impact of retropharyngeal lymph node metastases (RLNMs) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This meta-analysis was conducted according to PRISMA guidelines. INCLUSION CRITERIA: studies with more than 20 patients reporting the prevalence or prognostic impact of RLNMs in OPSCC. Whenever available, data on HPV status and subsites were extracted. RESULTS: Twenty-two articles were included. The overall prevalence of RLNMs in OPSCC was 13%, with no significant differences depending on HPV status. The highest prevalence was observed for posterior pharyngeal wall SCC (24%), followed by soft palate (17%), palatine tonsil (15%), and base of tongue (8%). RLNMs were associated with a significantly higher risk of death (HR:2.54;IC95%1.89-3.41) and progression (HR:2.44;IC95%1.80-3.30). CONCLUSIONS: The prevalence of RLNMs in OPSCC was 13%, being higher in tumors of the posterior pharyngeal wall. RLNMs were associated with unfavorable outcomes.

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New prognostic factors in oral squamous cell carcinoma (OSCC) (tumor-, host-, and environment-related) have been introduced recently to complete those traditionally considered. Among them, tumor volume (TV) could be the most interesting and applicable in clinical practice, considering the routine use of computed tomography in tumor staging. In this retrospective study we aimed to investigate whether a correlation exists among these new prognostic factors and survival outcomes.We collected data about 140 patients affected by OSCC who underwent primary surgery. Prognostic factors were collected and Overall Survival (OS), Disease Specific Survival (DSS) and Disease Free Survival (DFS) were estimated using Kaplan-Meier method; the Log-Rank test (Mantel-Cox) and Cox regression models were applied to investigate predictors of survival.The 5-year OS, DSS and DFS were 73.6 %, 89.2 % and 75.2 % respectively. Nodal metastasis (pN+), relapse and American Society of Anesthesiologists ASA-II were found independent prognostic factors for OS, and significantly associated to worst DSS (p 0.001). TV significantly correlated with higher relapse occurrence (p = 0.03).In our experience, lymph-node status, ASA classification and relapse significantly influenced DSS on univariate analysis. TV could represent an interesting additional parameter, since it significantly influenced DFS. However, prospective studies with standardized TV measurements and a greater number of patients are needed to validate this result.

BackgroundThe long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified.MethodsOlfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation.ResultsA total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent.ConclusionSix months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

Patients with coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide range of symptoms. In this paper, a detailed characterisation of mild-to-moderate ear, nose nd throat (ENT) symptoms is presented with the aim of recognising the disease early to help reduce further spread and progression.A total of 230 cases testing positive for SARS-CoV-2 and 134 negative controls were recruited for a case-control analysis. Symptoms were analysed using the Acute Respiratory Tract Infections Questionnaire, while other symptoms were investigated byAmong the study samples (n = 364), 149 were males and 215 were females with age ranging from 20 to 89 years (mean 52.3). Four main groups of symptoms were obtained: influenza-like symptoms, ENT-symptoms, breathing issues and asthenia-related symptoms, representing 72%, 69%, 64% and 53% of overall referred clinical manifestations, respectively. ENT symptoms, breathing issues and influenza-like symptoms were associated with positivity to SARS-CoV-2, whereas asthenia-related symptoms did not show a significant association with SARS-CoV-2 infection after controlling for other symptoms, comorbidities and demographic characteristics.ENT symptoms are equally represented with influenza-like ones as presenting symptoms of COVID-19. Patients with ENT symptoms should be investigated for early identification and prevention of SARS-CoV-2 spread.Importanza del rilevamento precoce dei sintomi ORL nella COVID-19 lieve-moderata.I pazienti con malattia da Coronavirus-19 (COVID-19) causata dal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) possono presentare una vasta gamma di sintomi. In questo articolo, è mostrata una caratterizzazione dettagliata dei sintomi nei pazienti con malattia lieve-moderata, al fine di riconoscere precocemente la malattia e ridurne l’ulteriore diffusione.Un totale di 230 pazienti risultati positivi per infezione da SARS-CoV-2 e 134 soggetti risultati invece negativi sono stati reclutati per questa analisi caso-controllo. I sintomi sono stati analizzati utilizzando l’Acute Respiratory Tract Infections Questionnaire, mentre altri, sono stati indagati mediante domande ad hoc.La popolazione oggetto dello studio era composta da 364 soggetti; 149 erano maschi e 215 femmine con età compresa tra 20 e 89 anni (media 52,3). Sono stati identificati quattro gruppi di sintomi: sintomi simil-influenzali, sintomi ORL, problemi respiratori e sintomi astenia-correlati che rappresentavano rispettivamente il 72%, 69%, 64% e 53% delle manifestazioni cliniche. Sintomi ORL, problemi respiratori e sintomi simil-influenzali erano associati a positività a SARS-CoV-2, mentre i sintomi correlati all’astenia non mostravano un’associazione significativa con l’infezione da SARS-CoV-2 dopo il controllo di altri sintomi, co-morbidità, e caratteristiche demografiche.I sintomi ORL sono ugualmente rappresentati rispetto a quelli simil-influenzali nell’esordio della COVID-19. I pazienti con sintomi ORL devono essere studiati per l’identificazione precoce e la prevenzione della diffusione del SARS-CoV-2.

Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000–2006 to 50% in 2019–2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.

Background: Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome. Here, we evaluated the prognostic value of LINE-1 methylation level in OPSCC patients, and further addressed the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation. Results: In this study, DNA was extracted from 163 formalin-fixed paraffin-embedded tissue samples retrospectively collected from stage III-IVB OPSCC patients managed with curative intent with up-front treatment. Quantitative methylation-specific PCR revealed that LINE-1 hypomethylation was directly associated with poor prognosis (5-year overall survival - OS: 28.1% for LINE-1 methylation Conclusions: Evaluation of the methylation level of LINE-1 may help in identifying the subset of OPSCC patients with bad prognosis regardless of their HPV status. Aberrant LINE-1 hypomethylation might occur along with TP53 mutations, and lead to altered gene expression in OPSCC. Citation Format: Mariateresa Casarotto, Valentina Lupato, Giorgio Giurato, Roberto Guerrieri, Sandro Sulfaro, Annamaria Salvati, Elisa D'Angelo, Carlo Furlan, Anna Menegaldo, Lorena Baboci, Barbara Montico, Irene Turturici, Riccardo Dolcetti, Salvatore Romeo, Vittorio Baggio, Stefania Corrado, Gianluca Businello, Maria Guido, Alessandro Weisz, Vittorio Giacomarra, Giovanni Franchin, Agostino Steffan, Luca Sigalotti, Emanuela Vaccher, Paolo Boscolo-Rizzo, Jerry Polesel, Giuseppe Fanetti, Elisabetta Fratta. LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1005.

Objectives of review: To review the literature for the evidence base for the aetiology and management of referred otalgia, looking particularly at non-malignant, neuralgic, structural and functional issues. Type of review: Systematic review. Search strategy: A systematic literature search was undertaken from the databases of EMBASE, CINAHL, MEDLINE®, BNI, and Cochrane Library according to predefined inclusion and exclusion criteria. Evaluation method: All relevant titles, abstracts and full text articles were reviewed by three authors who resolved any differences by discussion and consultation with senior author. Results: 44 articles were included in our review. The overall quality of evidence was low, with the vast majority of the studies being case-series with three cohort and four randomised-controlled trials included. The prime causes and management strategies were focussed on temporomandibular joint dysfunction (TMJD), Eagle syndrome and neuralgia. Our meta-analyses found no difference on the management strategies for the interventions found. Conclusions: Referred otalgia is common and treatment should be aimed at the underlying pathology. Potential aetiologies are vast given the extensive sensory innervation of the ear. An understanding of this and a structured approach to patient assessment is important for optimal patient management.

Background/Aims: Quantitative and qualitative alterations in the sense of smell are well established symptoms of COVID-19. Some reports have shown that non-neuronal supporting (also named sustentacular) cells of the human olfactory epithelium co-express ACE2 and TMPRSS2 necessary for SARS-CoV-2 infection. In COVID-19, syncytia were found in many tissues but were not investigated in the olfactory epithelium. Some studies have shown that syncytia in some tissues are formed when SARS-CoV-2 Spike expressed at the surface of an infected cell binds to ACE2 on another cell, followed by activation of the scramblase TMEM16F (also named ANO6) which exposes phosphatidylserine to the external side of the membrane. Furthermore, niclosamide, an approved antihelminthic drug, inhibits Spike-induced syncytia by blocking TMEM16F activity. The aim of this study was to investigate if proteins involved in Spike-induced syncytia formation, i.e., ACE2 and TMEM16F, are expressed in the human olfactory epithelium. Methods: We analysed a publicly available single-cell RNA-seq dataset from human nasal epithelium and performed immunohistochemistry in human nasal tissues from biopsies. Results: We found that ACE2 and TMEM16F are co-expressed both at RNA and protein levels in non-neuronal supporting cells of the human olfactory epithelium. Conclusion: Our results provide the first evidence that TMEM16F is expressed in human olfactory supporting cells and indicate that syncytia formation, that could be blocked by niclosamide, is one of the pathogenic mechanisms worth investigating in COVID-19 smell loss.

Background The COVID-19 pandemic has made wearing face masks a common habit in public places. Several reports have underlined the increased difficulties encountered by deaf people in speech comprehension, resulting in a higher risk of social isolation and psychological distress. Purpose To address the detrimental effect of different types of face masks on speech perception, according to the listener hearing level and background noise. Research Design Quasi-experimental cross-sectional study. Study Sample Thirty patients were assessed: 16 with normal hearing [NH], and 14 hearing-impaired [HI] with moderate hearing loss. Data Collection and Analysis A speech perception test (TAUV) was administered by an operator trained to speak at 65 dB, without a face mask, with a surgical mask, and with a KN95/FFP2 face mask, in a quiet and in a noisy environment (cocktail party noise, 55 dB). The Hearing Handicap Index for Adults (HHI-A) was administered twice, asking subjects to complete it for the period before and after the pandemic outburst. A 2-way repeated-measure analysis of variance was performed. Results The NH group showed a significant difference between the no-mask and the KN95/FFP2-mask condition in noise (p = 0.01). The HI group showed significant differences for surgical or KN95/FFP2 mask compared with no-mask, and for KN95/FFP2 compared with surgical mask, in quiet and in noise (p Conclusion Face masks have a detrimental effect on speech perception especially for HI patients, potentially worsening their hearing-related quality of life.

Funder: Ministero della Salute; doi: http://dx.doi.org/10.13039/501100003196, BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM

We have read with interest the recent article by Lerner et al.,which analyzed the clinical features of parosmia following coronavirus disease 2019(COVID-19). Congratulating the authors for the quality of their study, we would like to discuss some important points regarding pathogenetic hypotheses and the epidemiological implications emerging from their results.

Objectives/hypothesis The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. Study design Cross-sectional study. Methods Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' "HPV-driven" reference status, defined by presence of HPV-DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. Results Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV-driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%-100%) and a specificity of 100% (95% CI: 66%-100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%-99%) and a specificity of 100% (95% CI: 74%-100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV-DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. Conclusions We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low-invasive method to assess "HPV-driven" status in OPSCC and CUP. Level of evidence II Laryngoscope, 131:1042-1048, 2021.

Background: Both the prevalence of sinonasal inverted papilloma (IP) and the causal association with alpha-human papillomaviruses (alpha-HPVs) are controversial. In this study we aimed to determine HPV status in histologically selected, microdissected, formalin-fixed, and paraffin-embedded tissue samples of IP. Methods: HPV status was assessed retrospectively by polymerase chain reaction (PCR)-bead‒based multiplex genotyping on tissue samples of patients diagnosed with IP and consecutively treated with endoscopic resection. Forty-one HPV genotypes were considered, distinguishing between high risk and low risk. HPV status was correlated with demographics and clinical variables. Sixty sinonasal IP tissue samples were initially considered. After exclusion of 5 cases due to insufficient quality/quantity of the samples, 55 patients were included for analysis. Results: HPV-DNA sequences were identified in 34 of 55 (61.8%) IPs, with a higher prevalence of high-risk than low-risk HPV genotypes (19 [55.9%] and 15 cases [44.1%], respectively). HPV16 strongly prevailed among the high-risk HPV cases (84.2%), and HPV54 prevailed among the low-risk HPV cases (53.3%). IPs with origin within the maxillary sinus were significantly associated with high-risk HPV (p = 0.019). No significant associations emerged between HPV status and demographics or clinical variables. Conclusion: In a series of 55 IP tissue samples, HPV-DNA sequences were identified in 61.8% of cases, which differs from the data of previous investigations. Further case-control studies are advocated to confirm this prevalence in the Italian population addressed, and also to clarify any pathogenic involvement of HPV in the natural history of IPs.

BackgroundThe aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate COVID-19 in the period from January 17, 2022 to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients tested positive for SARS-CoV-2 infection between March and April, 2020 (comparator period).MethodsProspective study based on the sinonasal outcome tool 22 (SNOT-22), item “sense of smell or taste” and additional outcomes.ResultsPatients’ characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%; 95% CI, 27.6-37.8) was significantly lower from that during the comparator period (66.9%; 95% CI, 62.3-71.3) (ppppConclusionsThe prevalence and the severity of COVID-19 associated smell and taste dysfunction has dropped significantly with the advent of the Omicron variant.

COVID-19 related persistent olfactory disorders represent an unprecedented challenge

No abstract available

Objectives : Primary : To determine the rate of occult cervical metastasis in primary temporal bone squamous cell carcinomas (TBSSC). Secondary : to perform a subgroup meta-analysis of the risk of occult metastasis based on the clinical stage of the tumour and its risk based on corresponding levels of the neck Design : A systematic review and meta-analysis of papers searched through Medline, Cochrane, Embase, Scopus and Web of Science up to January 2021 to determine the pooled rate of occult lymph node/parotid metastases. Quality assessment of the included studies was assessed through the Newcastle-Ottawa scale. Setting : Centres around the world that perform surgery for TBSCC Participants : Patients with TBSCC Results : Overall, 9 out of 1034 screened studies met the inclusion criteria, for a total of 907 patients of which 388 had TBSCC. Out of the 191 patients who underwent a neck dissection, 21 had positive lymph nodes giving a pooled rate of occult metastases of 11% (95% CI: 7%-17%). When analysed using the Modified Pittsburg staging system, 21 pT2 cases had a pooled occult metastases rate of 3% (95% CI: 0%-21%), 27 pT3 cases had a pooled occult metastases rate of 12% (95% CI: 1%-60%), and 65 pT4 cases had a pooled occult metastases rate of 14% (95% CI: 7%-25%). Data available showed that most of the positive nodes were in Level II. Conclusion: The rate of occult cervical metastases in TBSCC increases based on the tumour (T) staging of the disease with majority of nodal disease found in level 2 of the neck.

The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID-19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient-reported outcome questionnaire from patients who developed symptomatic SARS-CoV-2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID-19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:419-421, 2022.

Background: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. Methodology: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. Results: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. Conclusion: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

We performed a review of the literature to identify studies that tested patients with flulike symptoms for SARS‐CoV‐2 infection by RT‐PCR and that reported data on the prevalence of loss of smell and/or taste. We identified a total of 6 studies (Fig. 1A).2, 4, 7‐10 Sensitivity and specificity were represented using forest plots, and pooled estimates were calculated using a random intercept logistic regression model. Publication bias was assessed by funnel plot. PPVs and NPVs were calculated as a function of prevalence of COVID‐19, ranging from 0% to 100%, using pooled sensitivity and specificity.

Background: A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)‐induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix. Methods: This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described. Results: The diagnostic gold standard for HPV‐related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples. Because most frequently available samples are formalin‐fixed paraffin‐embedded (FFPE), the pros and cons of the different approaches were analyzed. Conclusions: In the FFPE samples, the immunohistochemistry of p16, which is considered appropriate to assess HPV‐driven carcinogenesis in OPSCC according to the 8th American Joint Committee on Cancer TNM classification, may not be specific enough to become the diagnostic standard in the perspective of treatment deintensification. p16 may play a safer role in combination with another highly sensible assay. Other promising approaches are based on DNA detection through real‐time polymerase chain reaction and RNAscope.

Purpose The aim of our study is to evaluate the prevalence of different HPV genera – alpha, beta and gamma – in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease. Methods This retrospective observational study includes consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporization of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay. Results Twenty patients with JoRRP, aged 0.3–11 years old, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta – HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006). Conclusion Despite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.

ObjectivesThe aim of the present study was to develop and validate the CoronaVirus Disease – 2019 (COVID-19) Questionnaire (COVID-Q), a novel symptom questionnaire specific for COVID-19 patients, to provide a comprehensive evaluation which may be helpful for physicians.. A secondary goal of the present study was to evaluate the performance of the COVID-Q in identifying subjects at higher risk of being tested positive for COVID-19.Material and methodsConsecutive non-hospitalized adults who underwent nasopharyngeal and throat swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection at Treviso Hospital in March 2020, were enrolled. Subjects were divided into positive (cases) and negative (controls) in equal number. All of them gave consent and answered the COVID-Q. Patients not able to answer the COVID-Q due to clinical conditions were excluded.Parallel Analysis and Principal Component Analysis were used to identify clusters of items measuring the same dimension. The Item Response Theory (IRT)-based analyses evaluated the functioning of item categories, the presence of clusters of local dependence among items, item fit within the model and model fit to the data.ResultsAnswers obtained from 230 COVID-19 cases (113 males, and 117 females; mean age 55 years, range 20-99 years) and 230 controls (61 males, and 169 females; mean age 46 years, range 21-89) were analyzed. Parallel analysis led to the extraction of six components, which corresponded to as many clinical presentation patterns: asthenia, influenza-like symptoms, ear and nose symptoms, breathing issues, throat symptoms, and anosmia/ageusia. The final IRT models retained 27 items as significant for symptom assessment. The total score on the questionnaire was significantly associated with positivity to the molecular SARS-CoV-2 test: subjects with multiple symptoms were significantly more likely to be affected by COVID-19 (p < .001). Older age and male gender also represented risk factors. Presence of breathing issues and anosmia/ageusia were significantly related to positivity to SARS-CoV-2 (p < 0.001). None of the examined comorbidities had a significant association with COVID-19 diagnosis.ConclusionAccording to the analyses, COVID-Q could be validated since the aspects it evaluated were overall significantly related to SARS-CoV-2 infection. The application of the novel COVID-Q to everyday clinical practice may help identifying subjects who are likely to be affected by COVID-19 and address them to a nasopharyngeal swab in order to achieve an early diagnosis.What is already known about this topic?COVID-19 symptoms are widely known. Lots of studies have been published regarding self-administered questionnaires in order to characterize and know as much as possible regarding this disease. By the way, no specific questionnaires have been validated, yet, and there is no consensus regarding this topic.What does this article add?This paper shows the COVID-Q, a novel symptom questionnaire specific for COVID-19 patients. The aim is to provide a comprehensive evaluation that may be helpful to clinicians in order to suspect SARS-CoV-2 infection or not.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can cause a wide array of symptoms ranging from mild to severe or fatal forms of coronavirus disease 2019 (COVID-19). Furthermore, it has been observed that in a proportion of patients a variable range of symptoms may persist for a long time. An increasing number of studies have been focused on long COVID, but they have mainly been concentrated on previously hospitalized severe COVID-19 patients reporting symptoms up to 6-months after illness. The main aim of this study was to evaluate the prevalence of COVID-related symptoms 12-months after the onset of mild-to-moderate disease.

The aim of this study was to evaluate the CO

BackgroundIn a proportion of patients recovered from the acute COVID-19 phase, a variable range of symptoms has been observed to persist for at least 6-months.ObjectivesThe main aim of this study was to evaluate the prevalence of COVID-related symptoms 12-months after the onset of mild-to-moderate disease.MethodsProspective study based on structured questionnaires and additional outcomes.Results304/354 patients completing the survey at baseline also completed the follow-up interview (85.9%; median [range] age, 47 [18-76] years; 185 [60.9%] women). Persistence of at least one symptom at 12-months follow-up was reported by 161 patients (53.0%). The most commonly reported symptom of long COVID was felt tired (n=83, 27.3%), followed by smell or taste impairment (n=67, 22.0%), shortness of breath (n=39, 12.8%) and muscle pain (n=28, 9.2%). Being females (OR=1.64; 95% CI: 1.00-2.70), aged between 40-54 (OR=1.92; 95% CI: 1.07-3.44), having a BMI ≥25 (OR=1.67; 95% CI: 1.00-2.78), and experiencing more symptoms during the acute phase of the disease (OR=8.71 for ≥8 symptoms; 95% CI: 2.73-27.76) were associated with long COVID. Persistence of symptoms showed a significant impact on quality of life (pConclusionMore than half of patients with previous mild-to-moderate symptomatic COVID-19 complained the persistence of at least one symptom 12-months after the onset of the illness.