p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?

Laryngeal squamous cell carcinoma (LSCC) is a common malignancy that, despite scientific advancements, has not seen an improvement in its prognosis in the last decades. Few promising predictive markers have been found and none are relevant in clinical practice. p16ink4a, an oncosuppressor protein involved in cell cycle arrest, with a prognostic impact on other cancers, has been widely used in the head and neck region as a surrogate marker of HPV infection. Published papers and recent meta-analyses seem to minimize the biological role of HPV in the context of LSCC's cancerogenesis, and to disprove the reliability of p16ink4a as a surrogate prognostic marker in this context, while still highlighting its potential role as an independent predictor of survival. Unfortunately, the available literature, in particular during the last two decades, is often not focused on its potential role as an independent biomarker and few relevant data are found in papers mainly focused on HPV. The available data suggest that future research should focus specifically on p16ink4a, taking into account both its potential inactivation and overexpression, different patterns of staining, and immunohistochemistry cutoffs, and should focus not on its potential role as a surrogate marker but on its independent role as a predictor of survival.

Validity and reliability of the Questionnaire of Olfactory Disorders for Italian-speaking patients with olfactory dysfunction.

Objective: To translate and validate an Italian version of the Questionnaire of Olfactory Disorders (IT-QOD). Materials and methods: This is a prospective, multicentre study that involved patients with olfactory dysfunction (OD). Both cases and controls underwent administration of the IT-QOD, Sino-Nasal Outcome Test-22 (SNOT-22) and psychophysical evaluation of orthonasal and retronasal olfactory function. Results: The IT-QOD was administered to 96 patients and 38 controls. The Cronbach's alpha exceeded 0.90, indicating satisfactory internal consistency. The test-retest reliability was found to be high for both parosmia (rs = 0.944) and life quality (rs = 0.969). Patients with OD had significantly higher IT-QOD scores compared to healthy individuals (p < 0.001), indicating strong internal validity. The external validity was also satisfactory, as shown by the significant correlation with SNOT-22 (rs = -0.54) and the threshold, discrimination, and identification score (rs = -0.63). Conclusions: The IT-QOD was demonstrated to be reliable and valid to assess the impact of OD on the quality of life of Italian-speaking patients.

Vocal Fold Paralysis After Spinal and Epidural Anesthesia: A Case Report and Scoping Review.

OBJECTIVES: Cranial nerve paralysis is a rare complication of spinal and epidural anesthesia, and some cases of vocal fold paralysis (VFP) have been reported. The aim of this article is to report a case, identify evidence supporting the possibility of VFP being a complication of spinal and epidural anesthesia and to investigate the frequency, the characteristics, and the possible mechanisms of such a complication. DATA SOURCES: CINAHL Complete, Google Scholar, Cochrane Library, Pubmed, and EMBASE. METHODS: Case report according to CARE guidelines; scoping review according to PRISMA-ScR criteria. All types of studies that reported on patients of any age and sex, all types of spinal/epidural anesthesia regardless of the location and of drugs used were included. A data extraction sheet was completed for each study selected for inclusion based on the full-text screenings. Extracted data included: study characteristics, participant characteristics, intervention characteristics, outcome measures, clinical investigations. The study did not receive external funding. RESULTS: Eight studies met inclusion criteria and a total of 13 events (in 12 patients, including ours) were reported to date. Although there are some hypotheses in regard to the mechanism underlying the phenomena, including mechanical and inflammatory ones, the exact cause is still unclear. CONCLUSIONS: Only few cases of VFP after spinal or epidural anesthesia have been reported to date; however, it seems possible that VFP might be a potential underreported complication of such procedures. We believe that more research on the topic is warranted, especially considering the wide population potentially at risk. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Adenotonsillectomy in Children with Obstructive Sleep Apnea Syndrome: Clinical and Functional Outcomes.

Adenotonsillectomy (AT) is the first-line treatment for pediatric obstructive sleep apnea syndrome (OSAS). Relatively few studies have evaluated the clinical and functional outcomes of AT in children with OSAS, but these studies show that surgery improves behavior and quality of life (QOL). However, residual OSAS after AT is reported in severe cases. This study aimed to retrospectively evaluate the clinical and functional outcomes of AT in a cohort of children with OSAS. We consecutively enrolled children with OSAS who underwent AT and were admitted to our clinic from 1 July 2020 to 31 December 2022. For each participant, medical history and physical examinations were performed. Before and after surgery, all patients underwent a standard polygraphic evaluation, and caregivers completed the OSA-18 questionnaire. A total of 65 children with OSAS, aged 2-9 years, were included. After AT, 64 (98.4%) children showed a reduction in AHI, with median (IQR) values decreasing from 13.4/h (8.3-18.5/h) to 2.4/h (1.8-3.1/h) (p-value < 0.0001). Conversely, median (IQR) SpO2 nadir increased after surgery from 89% (84-92%) to 94% (93-95%) (p-value < 0.0001). Moreover, 27 children (18%) showed residual OSAS. The OSA-18 score decreased after AT from median (IQR) values of 84 (76-91) to values of 33 (26-44) (p-value < 0.0001). A positive significant correlation was found between OSA-18 post-operative scores and AHI post-operative scores (rho 0.31; p-value = 0.01). Our findings indicate that, in children with OSAS, AT is associated with significant improvements in behavior, QOL, and polygraphic parameters. However, long-term post-surgical follow-up to monitor for residual OSAS is highly recommended, especially in more severe cases.

Preoperative Diagnosis of Warthin Tumors Combining Cytological, Clinical and Ultrasonographic Information within a Multidisciplinary Approach in a Lump Clinic.

(1) Background: Warthin tumors account for about 20% of all benign salivary tumors, approaching 50% if we consider only the parotid gland. Wait and see is considered a reasonable option, but the diagnosis should be certain. Diagnosis can be based on morphological and cytological data, but the sensitivity of the fine needle aspiration cytology (FNAC) is not absolute, with a high rate of non-diagnostic findings in the event of a Warthin tumor, hindering the counseling and therapeutic decisions. The aim of the study is to evaluate the reliability of FNAC and its combination with anamnestic, clinical, and ultrasonographic data in diagnosing Warthin tumors. (2) Methods: A total of 413 patients affected by masses within the major salivary gland and managed between 2017 and 2022 at our institution have been included in the present retrospective study. Each patient underwent fine needle aspiration biopsy (FNAB) with a subsequent cytological diagnosis; successively, for each patient, the clinician (otolaryngologist) and the histopathologist discussed the combination of cytological (even non-diagnostic), clinical, and ultrasonographic data in order to make a "multiparametric" diagnosis. A total of 214 cases were subsequently submitted to surgical resection and had a final histopathology report, to which the cytological and the multiparametric diagnoses can be compared. We extracted all the patients with a cytological, multiparametric, and/or histological diagnosis of Warthin tumors in order to assess the sensitivity and specificity of FNAC and of multiparametric analysis in diagnosing Warthin tumors in case of a major salivary gland mass. (3) Results: One hundred thirty-two cases had a cytological, multiparametric, and/or histological diagnosis of Warthin tumors. FNAC displays a sensitivity of 68.4% and a specificity of 98.7% in diagnosing Warthin tumors. The multiparametric evaluation allowed a considerable improvement in sensitivity (92.9% vs. 68.4%), minimizing the number of non-diagnostic results and preserving at the same time a similar value of specificity (95.5% vs. 98.7%). Notably, none of the patients with a cytological or multiparametric diagnosis of Warthin were affected by a malignant lesion in the final histopathological report. (4) Conclusions: In the case of Warthin tumors, a multiparametric evaluation encompassing anamnestic, clinical, and cytological data is effective in reducing the number of non-diagnostic reports and can safely guide the management of a tumor (e.g., antibiotic treatment of infectious complications, assign a low priority to surgery, even consider observation avoiding surgery) which is absolutely benign and can be associated with no clinically relevant issues.

Evaluation of Staging Systems for Cancer of the Nasal Vestibule.

Squamous cell carcinoma of the nasal vestibule is reported to account for less than one percent of all head and neck malignancies. It lacks a designated WHO ICD-O topography code, and multiple systems are available for the staging of this disease, which results in unwanted variability and the subsequent poor reliability of data. The aim of this study was to evaluate the currently available staging systems for cancer of the nasal vestibule, including the recently introduced classification by Bussu et al., which built on Wang's original concept but with clearer anatomical cutoffs. Different staging systems for cancer of the nasal vestibule (UICC nasal cavity, UICC skin cancer of the head and neck, Wang and Bussu et al.) were evaluated via a retrospective analysis of 148 patients. The staging system, per Bussu et al., had the most balanced allocation of patients among the stages. When using the Wang classification as a reference, stage migration occurred less frequently with the Bussu classification. The widespread adoption of a single staging system, as well as the introduction of a designated topography code for cancer of the nasal vestibule, could lead to more uniformity in data reporting and improve an understanding of the incidence and disease outcome. The newly proposed carcinoma of the nasal vestibule classification by Bussu et al. has the potential to improve the staging and allocation among stages. Further analysis of survival data is needed to assess which classification system is best suited for nasal vestibule carcinoma.

New standards for the management of nose vestibule malignancies.

BACKGROUND: Nasal vestibule squamous cell carcinoma (NVSCC) is an ill-defined underestimated condition. AIM/OBJECTIVE: To define the current standard of care. MATERIAL AND METHODS: We review recent acquisitions concerning clinical features and therapeutic approaches. RESULTS: The current AJCC staging system, which attributes to nasal vestibule the same topographic code as nasal cavity proper and the same T-classification criteria as ethmoid, appears inadequate.As for treatment of primary lesions without bone invasion, current evidence suggests that brachytherapy is at least equivalent to surgery and superior to external beams in terms of oncological outcomes, and superior to both modalities in terms of cosmesis and function. CONCLUSIONS: As for classification and staging, the nasal vestibule should be defined as a subsite of the nose and paranasal sinuses, distinct from the 'nasal cavity proper and ethmoid', with specific topographic code and T-classification criteria. This will improve the assessment of prognosis and prevalence, underestimated also because of misdiagnosis with skin cancers.Secondly, brachytherapy should become the new standard for the treatment of primary lesions without bone invasion. To optimize the advantages of brachytherapy, we propose novel anatomic criteria for the implantation. SIGNIFICANCE: Increasing evidence supports a paradigm shift in staging and treatment of NVSCC.

Do We Have Enough Evidence to Specifically Recommend Transoral Robotic Surgery in HPV-Driven Oropharyngeal Cancer? A Systematic Review.

Introduction: International guidelines include transoral robotic surgery (TORS) as an option for selected oropharyngeal squamous cell carcinomas (OPSCCs). In the perspective of treatment de-intensification, many surgeons have started recommending and performing TORS preferentially in p16- positive OPSCC in order to reduce the long-term morbidity related to chemoradiotherapy. The aim of the present review is to analyze the current evidence supporting the above-cited strategy. Materials and Methods: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Twenty-two studies were included in this review, with a total of 3992 patients treated with primary TORS. The majority of patients were classified as HPV+ (n = 3655, 91.6%), and 8.2% (n = 327) as HPV-. The HPV status was unknown in only 10 (0.3%) patients. In particular, only five of the included studies compared survival outcomes of HPV-positive patients with HPV-negative ones treated with primary TORS, and only two of these found a significant improvement in survival in the HPV-driven cohort. Discussion: The current literature does not clarify whether HPV+ OPSCCs treated with TORS, alone or with adjuvant treatments, are associated with a better oncologic and/or functional outcome compared to those treated with radio- or chemoradiotherapy. However, TORS alone obtained good oncological outcomes in a high percentage of cases in the reviewed series. Recent data, on the other hand, suggest that TORS could represent a promising strategy for intensifying treatments in HPV- OPSCC.

Accuracy of p16 IHC in Classifying HPV-Driven OPSCC in Different Populations.

High-risk human papillomavirus (HPV) infection is a defined etiopathogenetic factor in oropharyngeal carcinogenesis with a clear prognostic value. The P16 IHC (immunohistochemistry) is a widely accepted marker for HPV-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC); in the present paper, we discuss its reliability as a standalone marker in different populations. The literature suggests that rates of p16 IHC false positive results are inversely correlated with the prevalence of HPV-driven carcinogenesis in a population. We propose a formula that can calculate such a false positive rate while knowing the real prevalence of HPV-driven OPSCCs in a given population. As it has been demonstrated that p16 positive/HPV negative cases (i.e., false positives at p16 IHC) have the same prognosis as p16 negative OPSCC, we conclude that despite the valuable prognostic value of p16 IHC, relying only on a p16 IHC positive result to recommend treatment de-intensification could be risky. For this aim, confirmation with an HPV nucleic acid detection system, especially in areas with a low prevalence of HPV-related OPSCCs, should be pursued.

Electrocautery, Harmonic, and Thunderbeat Instruments in Parotid Surgery: A Retrospective Comparative Study.

The aim of this retrospective study has been to compare the surgical outcomes of patients undergoing superficial parotidectomy with three different instruments: bipolar electrocautery, ultrasound, and mixed energy instruments. The clinical records of 102 patients who had undergone superficial parotidectomy for benign tumors between January 2016 and April 2022 were considered. Based on the tool used during the surgery, the patients were divided into three study groups: classic electrocautery hemostasis group (CH group), ultrasonic instrument group (HA group), and combined energy instrument group (TB group). The duration of surgery, the total post-operative drainage volume, and the intra-operative blood loss were significantly higher in the CH group compared to the HA and the TB group, while the differences were not significant between the latter two groups. Facial nerve weakness was detected in 45.9% of the CH group, 12.5% of the HA group, and 21.2% of the TB group. The rate of facial nerve dysfunction in the CH group was significantly higher than in the HA group (0.011). In the patients who experienced post-operative facial nerve dysfunction, the recovery time was significantly shorter in the HA group compared to the CH and the TB group. The HA and TB groups have demonstrated comparable and significantly better surgical outcomes than bipolar electrocautery. Ultrasound instruments have been shown to cause, in comparison with the other techniques, a lower rate of temporary facial nerve dysfunction and, if this is present, lead to a faster spontaneous recovery time.

The Absence of Permanent Sensorineural Hearing Loss in a Cohort of Children with SARS-CoV-2 Infection and the Importance of Performing the Audiological "Work-Up".

BACKGROUND: Currently, the novel coronavirus (SARS-CoV-2) causes an acute respiratory illness named COVID-19 and is a controversial risk factor for hearing loss (HL). Herein, we aim to describe the associated symptoms and to evaluate hearing function in the COVID-19 pediatric population. METHODS: A retrospective cross-sectional observational study was carried out on 37 children who contracted COVID-19 infection with no previous audio-vestibular disorders. Clinical data on the infections were collected, and an audiological assessment of all affected children was performed by using different diagnostic protocols according to their age. RESULTS: Fever, upper respiratory and gastrointestinal manifestations were common presentations of infection. Audiological function was normal in 30 (81.08%) children, while 7 children showed an increased hearing threshold: 6 (16.21%) had transient conductive hearing loss (CHL) due to middle ear effusion and normalized at the follow-up and 1 had sensorineural hearing loss (SNHL). A single child was affected by bilateral SNHL (2.7%); however, he underwent a complete audiological work-up leading to a diagnosis of genetic HL due to a MYO6 gene mutation which is causative of progressive or late onset SNHL. CONCLUSIONS: HL needs to be considered among the manifestations of COVID-19 in children, nevertheless, we found cases of transient CHL. The onset of HL during or following COVID-19 infection does not eliminate the indication for maintaining audiological surveillance and audiological work-ups, including genetic diagnosis, to avoid the risk of mistaking other causes of HL.

Reliability of a Multidisciplinary Multiparametric Approach in the Surgical Planning of Laryngeal Squamous Cell Carcinomas: A Retrospective Observational Study.

(1) Background: Endoscopy and morphological imaging are the mainstay of the diagnostic work up of laryngeal squamous cell carcinomas (LSCCs), which can be integrated in a multidisciplinary discussion to obtain a shared pretreatment staging. (2) Methods: A retrospective evaluation of patients, managed at a tertiary university hospital in Italy and submitted to major laryngeal surgery, has been performed. Four different stagings have been defined and compared: epTN (based on endoscopy and physical ENT examination); radTN (based on CT scan); cTN (based on multidisciplinary integration of the two above); pTN based on pathology on surgical samples. Oncological outcomes have been assessed. (3) Results: Three-year relapse free and disease specific survival were 88% and 92.5%, respectively, without significant differences between partial surgeries (n = 13) and total laryngectomies (n = 32). As for the pretreatment staging, and in particular the T classification, the cTN has been revealed as more reliable than epTN and radTN alone in predicting the final pT (Cohen kappa coefficient: 0.7 for cT, 0.44 for radT, 0.32 for epT). In the partial surgery group, we did not record any positive margin nor local recurrence, with a 100% overall and disease-specific survival. (4) Conclusions: The multidisciplinary approach is fundamental in the definition of the primary lesion in LSCC, in particular in order to safely perform surgical preservation of laryngeal function, which is associated with a higher laryngectomy-free survival than irradiation but to a lower salvageability in case of recurrence.

Low Prevalence of HPV Related Oropharyngeal Carcinogenesis in Northern Sardinia.

HPV infection is a clear etiopathogenetic factor in oropharyngeal carcinogenesis and is associated with a markedly better prognosis than in smoking- and alcohol-associated cases, as specified by AJCC classification. The aim of the present work is to evaluate the prevalence of HPV-induced OPSCC in an insular area in the Mediterranean and to assess the reliability of p16 IHC (immunohistochemistry) alone, as accepted by AJCC, in the diagnosis of HPV-driven carcinogenesis in such a setting. All patients with OPSCC consecutively managed by the referral center in North Sardinia of head and neck tumor board of AOU Sassari, were recruited. Diagnosis of HPV-related OPCSS was carried out combining p16 IHC and DNA testing on FFPE samples and compared with the results of p16 IHC alone. Roughly 14% (9/62) of cases were positive for HPV-DNA and p16 IHC. Three more cases showed overexpression of p16, which has a 100% sensitivity, but only 75% specificity as standalone method for diagnosing HPV-driven carcinogenesis. The Cohen's kappa coefficient of p16 IHC alone is 0.83 (excellent). However, if HPV-driven carcinogenesis diagnosed by p16 IHC alone was considered the criterion for treatment deintensification, 25% of p16 positive cases would have been wrongly submitted to deintensified treatment for tumors as aggressive as a p16 negative OPSCC. The currently accepted standard by AJCC (p16 IHC alone) harbors a high rate of false positive results, which appears risky for recommending treatment deintensification, and for this aim, in areas with a low prevalence of HPV-related OPSCC, it should be confirmed with HPV nucleic acid detection.

Audiological Risk Factors, Referral Rates and Dropouts: 9 Years of Universal Newborn Hearing Screening in North Sardinia.

Background: Objectives of the present work were to analyze the prevalence of hearing loss in our population of screened newborns during the first 9 years of the universal newborn hearing screening (UNHS) program at University Hospital Sassari (Italy) (AOU Sassari), to analyze the risk factors involved, and to analyze our effectiveness in terms of referral rates and dropout rates. Methods: Monocentric retrospective study whose target population included all the newborns born or referred to our hospital between 2011 and 2019. Results: From 2011 to 2019, a total of 11,688 babies were enrolled in our screening program. In total, 3.9‱ of wellborn babies and 3.58% of neonatal intensive care unit (NICU) babies had some degree of hearing loss. The most frequently observed risk factors among non-NICU babies were family history of hearing loss (3.34%) and craniofacial anomalies (0.16%), among NICU babies were low birth weight (54.91%) and prematurity (24.33%). In the multivariate analysis, family history of hearing loss (p < 0.001), NICU (p < 0.001), craniofacial anomalies (p < 0.001), low birth weight (<1500 g) (p = 0.04) and HIV (p = 0.03) were confirmed as risk factors. Conclusions: Our data are largely consistent with the literature and most results were expected, one relevant exception being the possible role of NICU as a confounding factor and the limited number of risk factors confirmed in the multivariate analysis.

The Impact of COVID-19 on Universal Newborn Hearing Screening.

OBJECTIVES: To report the direct and indirect impact of coronavirus disease 2019 pandemic on the Universal Newborn Hearing Screening program of our institution (Azienda Ospedaliero Universitaria di Sassari). DESIGN: Monocentric retrospective study whose target population included all the newborns born in or referred to our hospital in 2019 and 2020. RESULTS: There is no statistically significant difference in time to retest or loss to follow-up rate between the 2 years considered (2019 to 2020). Referral rate is not higher for newborns born to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction positive mothers. CONCLUSIONS: In relation to the analyzed variables, coronavirus disease 2019 seems to have a limited impact on our screening program. Severe acute respiratory syndrome coronavirus 2 did not behave as an audiological risk factor in our series.

Prevalence of HPV Infection and p16INK4a Overexpression in Surgically Treated Laryngeal Squamous Cell Carcinoma.

Background: The mucosal high-risk (HR) human papillomavirus (HPV) is associated with oropharyngeal carcinogenesis. Aims of this study were to evaluate the prevalence of HR-HPV infection in laryngeal squamous cell carcinoma (LSCC) from different subsites, and the clinico-biological meaning of p16 overexpression. Methods: Ninety-seven LSCCs submitted to primary surgery (n = 75) or to post-irradiation salvage laryngectomy (n = 22) were evaluated for HR-HPV DNA and RNA using Luminex-based assays. p16 immunohistochemistry was performed. Results: HR-HPV DNA from HPV16 was detected in seven cases (8.75%), without significant differences between supraglottic and glottic lesions. HPV RNA was never detected. p16 overexpression correlated with HR-HPV DNA, but the kappa agreement score was poor. HPV DNA showed no impact on prognosis. p16 overexpression was associated with a better survival (OS, RFS) in primarily operated cases, while an inverse association with OS was observed in the salvage surgery group. Conclusions: HR-HPV infection appears to have a marginal role in LSCC independent of the anatomical subsite. p16 expression is deregulated in LSCC independent of HPV but displays a prognostic role in patients submitted to primary surgery. The negative predictive role of p16 overexpression in patients undergoing salvage surgery deserves more investigations for validation and elucidation of its clinical relevance.

"Swab Team" in the SARS-CoV-2 outbreak containment among healthcare workers.

INTRODUCTION: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing. METHODOLOGY: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated. RESULTS: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001). CONCLUSIONS: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection).

A prospective pilot study on the effects of endoscopic sinus surgery on upper and lower airway performance.

OBJECTIVE: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease. METHODS: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated. RESULTS: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1st second (FEV1) significantly improved after surgery from 3.23 to 3.45 L/s. CONCLUSIONS: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.