OBJECTIVE:One legacy of the COVID-19 pandemic has been an increase in electronic health record (EHR) patient-generated messages to providers, which has increased the amount of time providers spend on EHR tasks. We sought to evaluate clinical and demographic variables associated with high EHR patient message generation in a head and neck oncologic surgery (HNS) clinic. METHODS:A randomized 20% sample of unique outpatient visits to the HNS service at a tertiary academic medical center from July to December 2023 was retrospectively reviewed. Patient-generated EHR messages to providers for 6 months following the index visit date were categorized by quintiles, with high-utilizers defined as the top quintile. RESULTS:High-utilizers sent a greater number of messages (mean, 27.6 [range: 8-110] vs. 3.2 [1-7], p < 0.001). On multivariable regression analysis, high-utilizers were less likely to be elderly (OR = 0.13 [95% CI 0.04-0.52]), single (OR = 0.44 [0.19-0.98]), and more likely to have malignancy (OR = 2.27 [1.27-4.04]), advanced comorbidity (OR = 5.33 [1.71-16.53]), surgical treatment (OR = 3.16 [1.78-5.58]), and a specific provider (OR = 4.20 [1.21-14.53]). Sex, payor status, location, and new vs. established patient status were not associated with high-utilization. CONCLUSION:Within an academic HNS practice, patients with malignant disease, comorbidity, surgical patients, and those who saw a specific provider were more likely to be high-utilizers, while older patients were less likely to use EHR messaging. These data suggest that some patient populations require more personalized and frequent support to address communication needs and raise concern about the ability of elderly patients to use electronic communications, who may have unmet needs. LEVEL OF EVIDENCE:NA.

AbstractObjectivesHypoglossal nerve stimulation (HGNS) is a promising surgical option for patients with obstructive sleep apnea (OSA) who are intolerant of continuous positive airway pressure therapy (CPAP). Efficacy studies for HGNS stimulation largely focus on the apnea–hypopnea index and/or oxygen desaturation index. This study's objective was to show the physiological effects of HGNS stimulation on upper airway patency, airflow, and treatment effect during polysomnography (PSG) testing.MethodsPSG tracings from patients implanted with an Inspire© HGNS device were reviewed for this study. Nasal pressure was utilized as a surrogate for respiratory flow and chin electromyography was used to detect HGNS stimulation, allowing for breath‐to‐breath analysis. Per our sleep laboratory protocol, the HGNS device was turned on and off at different periods of the night. Respiratory tracings during these periods were visually analyzed.ResultsAnalysis of on–off periods of HGNS therapy during PSG allows for a concise assessment of HGNS efficacy. The presence of inspiratory flow limitation and subsequent apneas or hypopneas upon turning off HGNS stimulation with restoration of stable, unobstructed breathing upon resuming HGNS stimulation indicates a positive treatment effect related to HGNS therapy. Despite the respiratory‐sensing capacity of the Inspire HGNS device, desynchrony of stimulation and inspiration is observed. Desynchrony yields partially captured inspiratory cycles, allowing for assessment of HGNS effect on an individual breath.ConclusionNight‐to‐night and intranight variability in OSA severity makes assessing the effect of HGNS complex. Strategic testing protocols during postoperative PSG can provide critical insight into the effect of this therapy on upper airway obstruction during sleep. On–off periods of stimulation provide a concise assessment of the effect of HGNS on preventing upper airway collapse and help to account for night‐to‐night and intranight variability. Respiratory desynchrony associated with HGNS therapy exists. Observing partially‐stimulated inspiratory cycles allow for assessment of HGNS's effect on a single breath.Level of Evidence4.

Objective Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery. Study Design The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile. Methods Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality. Results Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44]). Conclusions High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals.

The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep.

Rationale The THN3 randomized, controlled trial demonstrated that targeted hypoglossal nerve stimulation (THN) was associated with substantial improvement in sleep-disordered breathing over 11 months of therapy in moderate to severe obstructive sleep apnea (OSA) with a favorable safety profile. Subjects receiving THN fared significantly better than control patients with inactive THN. This investigation shall describe the 3-year safety and efficacy results from THN3.

Einleitung In der randomisiert kontrollierten THN3-Studie führte die gezielte Hypoglossusstimulation (THN) nach 11 Monaten Therapie bei geringer Morbidität zu einer substanziellen Verbesserung der obstruktiven Schlafapnoe (OSA), insbesondere zeigte sich eine signifikante überlegenheit gegenüber einer Kontrollgruppe mit inaktiver Therapie. Hier werden Sicherheit und Wirksamkeit über einen längeren Zeitraum dargestellt.

OBJECTIVE:This study examines the association between patient-reported allergy history and immune checkpoint inhibition (ICI) response in patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). STUDY DESIGN:Retrospective cohort study. SETTING:Academic tertiary care hospital. METHODS:Data were collected from the electronic medical records on baseline age, sex, allergy history, human papillomavirus status, T-stage, N-stage, smoking status, and survival for patients with and without an allergy history. The primary outcome was ICI response defined as complete or partial response by the RECIST criteria. Chi-square and logistic regression analyses were conducted to compare rates and odds of ICI response. Kaplan-Meier analyses were used to compare survival between groups. RESULTS:Our study included 52 patients with an allergy history and 36 patients without an allergy history. The groups were similar in age, sex, HPV status, smoking status, and T- and N-stage. Patients with an allergy history (17/52, 32.1%) had a greater ICI response rate than patients without allergy history (4/36, 11.1%) (P = .02). After adjusting for HPV, patients with allergies had 3.93 (1.19-13.00) times increased odds of ICI response compared to patients without allergies. The median progression-free survival was 6.0 and 4.2 months for patients with and without an allergy history respectively (log-rank, P = .04). The median overall survival was 25.0 and 11.1 months for patients with and without an allergy history respectively (log-rank, P = .002). CONCLUSION:Patient-reported allergy history was associated with ICI response in patients with RMHNSCC, underscoring the potential clinical utility of allergy history in estimating ICI response.

OBJECTIVES:To explore the impact of pre-existing comorbidities on immunotherapy response, overall and progression-free survival, and immune-related adverse events (irAEs) of patients with advanced head and neck cancer (HNC) treated with immunotherapy. PATIENTS AND METHODS:Ninety-three patients treated with immunotherapy were identified and stratified into comorbidity absent or present (CCI < 1 and CCI ≥ 1, respectively) cohorts, and clinical outcomes were compared between these two groups. RESULTS:Patients with no comorbidities had longer overall survival (aHR = 2.74, 95% CI [1.18, 6.40], p = 0.02) and progression-free survival (aHR = 2.07, 95% CI [1.03, 4.16], p = 0.04) and a higher tumor response rate (32% in CCI < 1 vs. 14% in CC ≥ 1, p = 0.05). Risk for irAEs was higher in the comorbidity absent group (p = 0.05). CONCLUSION:Comorbidity should be considered as a significant prognostic factor in clinical decision-making for patients with advanced HNC undergoing immunotherapy.

BACKGROUND:Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category.METHODS:Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category.RESULTS:The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%).CONCLUSIONS:The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Importance:Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors.Objective:To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival.Design, Setting, and Participants:This cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021.Main Outcomes and Measures:Positivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites.Results:The study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male [73.9%]; mean [SD] age, 59.5 [10.8] years) and 254 (33.1%) with CESC (mean [SD] age, 48.7 [14.1] years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio [aHR], 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% [95% CI, 84.8%-99.9%] vs 45.8% [95% CI, 28.3%-74.1%]; HR, 0.10 [95% CI, 0.03-0.30]; P = .009).Conclusions and Relevance:In this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-positive nonoropharyngeal cancer.

ObjectiveTo examine the relationship between surgeon volume and operative morbidity and mortality for laryngectomy.Data SourcesThe Nationwide Inpatient Sample was used to identify 45,156 patients who underwent laryngectomy procedures for laryngeal or hypopharyngeal cancer between 2001 and 2011. Hospital and surgeon laryngectomy volume were modeled as categorical variables.MethodsRelationships between hospital and surgeon volume and mortality, surgical complications, and acute medical complications were examined using multivariable regression.ResultsHigher‐volume surgeons were more likely to operate at large, teaching, nonprofit hospitals and were more likely to treat patients who were white, had private insurance, hypopharyngeal cancer, low comorbidity, admitted electively, and to perform partial laryngectomy, concurrent neck dissection, and flap reconstruction. Surgeons treating more than 5 cases per year were associated with lower odds of medical and surgical complications, with a greater reduction in the odds of complications with increasing surgical volume. Surgeons in the top volume quintile (>9 cases/year) were associated with a decreased odds of in‐hospital mortality (OR = 0.09 [0.01–0.74]), postoperative surgical complications (OR = 0.58 [0.45–0.74]), and acute medical complications (OR = 0.49 [0.37–0.64]). Surgeon volume accounted for 95% of the effect of hospital volume on mortality and 16%–47% of the effect of hospital volume on postoperative morbidity.ConclusionThere is a strong volume‐outcome relationship for laryngectomy, with reduced mortality and morbidity associated with higher surgeon and higher hospital volumes. Observed associations between hospital volume and operative morbidity and mortality are mediated by surgeon volume, suggesting that surgeon volume is an important component of the favorable outcomes of high‐volume hospital care. Laryngoscope, 133:834–840, 2023

BACKGROUNDHuman papillomavirus (HPV) is responsible for a growing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) among men and White individuals. Whether similar trends apply to women, non‐Whites, and non‐oropharyngeal squamous cell carcinomas (non‐OPSCCs) is unknown.METHODSThis is a cross‐sectional analysis combining 2 multi‐institutional case series of incident head and neck squamous cell carcinoma (HNSCC) cases. Incident HNSCCs from 1995 to 2012 were enrolled retrospectively using banked tumor samples and medical record abstraction. Incident HNSCCs from 2013 to 2019 were enrolled prospectively. The prevalence of tumor HPV biomarkers was tested over 3 time periods (1995‐2003, 2004‐2012, and 2013‐2019). Centralized testing was done for p16 immunohistochemistry (p16) and oncogenic HPV in situ hybridization (ISH).RESULTSA total of 1209 incident cases of HNSCC were included. Prevalence of p16‐ and ISH‐positive tumors increased significantly for oropharynx cancers over time. The majority were positive after 2013 for White patients (p16, 92%; P < .001; ISH 94%; P < .001), Black patients (p16, 72%; P = .021; ISH 67%; P = .011), and Hispanic patients (p16, 100%; P = .04; ISH 100%; P = .013). For women with OPSCC, the prevalence of p16‐ and ISH‐positive tumors increased significantly to 82% (P < .001) and 78% (P = .004), respectively. For non‐OPSCCs, there was increased p16 and ISH positivity overall with 24% p16 and 16% ISH positivity in the most recent time period (P < .001 for both).CONCLUSIONSThe majority of OPSCCs in US tertiary care centers are now p16 and ISH positive for all sex and race groups. In some populations in the United States, 91% of OPSCCs are now caused by HPV. Few non‐OPSCCs are p16 and ISH positive.

Pain management is an important consideration for Head and Neck Cancer (HNC) patients as they are at an increased risk of developing chronic opioid use, which can negatively impact both quality of life and survival outcomes. This retrospective cohort study aimed to evaluate pain, opioid use and opioid prescriptions following HNC surgery. Participants included patients undergoing resection of a head and neck tumor from 2019–2020 at a single academic center with a length of admission (LOA) of at least 24 h. Exclusion criteria were a history of chronic pain, substance-use disorder, inability to tolerate multimodal analgesia or a significant post-operative complication. Subjects were compared by primary surgical site: Neck (neck dissection, thyroidectomy or parotidectomy), Mucosal (resection of tumor of upper aerodigestive tract, excluding oropharynx), Oropharyngeal (OP) and Free flap (FF). Average daily pain and total daily opioid consumption (as morphine milligram equivalents, MME) and quantity of opioids prescribed at discharge were compared. A total of 216 patients met criteria. Pain severity and daily opioid consumption were comparable across groups on post-operative day 1, but both metrics were significantly greater in the OP group on the day prior to discharge (DpDC) (5.6 (1.9–8.6), p < 0.05; 49 ± 44 MME/day, p < 0.01). The quantity of opioids prescribed at discharge was associated with opioid consumption on the DpDC only in the Mucosal and FF groups, which had longer LOA (6–7 days) than the Neck and OP groups (1 day, p < 0.001). Overall, 65% of patients required at least one dose of an opioid on the DpDC, yet 76% of patients received a prescription for an opioid medication at discharge. A longer LOA (aOR = 0.82, 95% CI: 0.63–0.98) and higher Charlson Comorbidity Index (aOR = 0.08, 95% CI: 0.01–0.48) were negatively associated with receiving an opioid prescription at the time of discharge despite no opioid use on the DpDC, respectively. HNC patients, particularly those with shorter LOA, may be prescribed opioids in excess of their post-operative needs, highlighting the need the for improved pain management algorithms in this patient population. Future work aims to use prospective surveys to better define post-operative and outpatient pain and opioid requirements following HNC surgery.

IntroductionA yield of ≥18 nodes from neck dissection has been shown to be associated with improved locoregional recurrence rates and survival. We sought to determine factors associated with lymph node yields below this threshold.Materials and MethodsA retrospective review of patients who underwent neck dissection as part of definitive surgical treatment for mucosal head and neck squamous cell carcinoma (SCC) between January 2015 and December 2018 at an academic tertiary referral center was performed. Patients with a history of prior radiation or neck dissection were excluded.ResultsThere were 412 neck dissections performed in 323 patients. Specimens containing <18 nodes decreased from 16.2% in 2015–2016 to 7.4% of neck dissections in 2017–2018. The proportion of neck dissections removing <3 levels decreased from 9.1% of neck dissections in 2015–2016 to 4.0% in 2017–2018. Multivariable regression analysis demonstrated that dissection of ≥3 levels (OR = 0.2 [0.1–0.4]) and neck dissection in 2017–2018 compared to 2015–2016 (OR = 0.4 [0.2–0.8]) were significantly associated with a lower odds of <18 nodes. Stage, site, race, sex, human papillomavirus status, positive nodes, surgeon volume, and pathologist volume were not associated with neck dissection specimens with <18 nodes, after controlling for all other variables.ConclusionsIncreased recognition of the importance of node count as a quality indicator, and the extent of neck dissection is associated with increased nodal yield from neck dissection. These data suggest that node count can be used as a quality measure of neck dissection for mucosal SCC.Level of Evidence4 Laryngoscope, 133:2160–2165, 2023

Given the recent successes of anti-PD-1 immunotherapy, many clinical trials have sought to assess the safety and efficacy of this treatment modality in the neoadjuvant setting. This systematic review provides a comprehensive summary of findings from neoadjuvant head and neck cancer immunotherapy clinical trials with a focus on PD-1/PD-L1 axis blockade. Pubmed, Embase, Cochrane Library, Web of Science, Google Scholar, and were systematically searched for all eligible neoadjuvant head and neck cancer immunotherapy clinical trials. Eight clinical trials met the inclusion criteria comprising a total of 260 patients. Study drugs included nivolumab, pembrolizumab, ipilimumab, durvalumab, and tremelimumab. The overall mean objective response rate (ORR) was 45.9 +/- 5.7% with a 41.5 +/- 5.6% single agent mean ORR. There were no deaths due to immune-related toxicities. Neoadjuvant immunotherapy for mucosal head and neck squamous cell cancer has demonstrated favorable response rates with no unexpected immune-related toxicities in phase I/II clinical trials.