OBJECTIVE:To compare facial nerve function and perioperative outcomes among antegrade, retrograde, and extracapsular parotidectomy approaches in benign and malignant tumors. STUDY DESIGN:Retrospective review. SETTING:Tertiary academic center. METHODS:Adults undergoing parotidectomy with facial nerve preservation between 2018 and 2023 were included. Demographic, surgical, and outcome variables were analyzed using bivariate and multivariable regression. RESULTS:A total of 740 tumors were analyzed (353 benign, 387 malignant). Antegrade dissection was performed in 288 cases (194 malignant), retrograde in 334 (167 malignant), and extracapsular in 118 (26 malignant). Transient and permanent facial weakness occurred in 20% and 5% of cases. After adjustment, extracapsular dissection (odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.1-0.7, P = .0058) significantly reduced transient weakness compared with antegrade dissection. Retrograde dissection (OR = 0.5, 95% CI 0.3-1.1, P = .11) demonstrated a trend toward lower rates of transient weakness relative to antegrade dissection. In malignant tumors, outcomes were similar across approaches. Extracapsular dissection was rarely used in malignant disease and reserved for selected cases. Antegrade dissection had longer operative times in benign and malignant tumors (P < .001). Perioperative complication rates, unplanned visits, recurrence, re-operations, ED visits, and readmissions were low and not significantly different across techniques. CONCLUSION:In benign parotidectomy, extracapsular dissection significantly reduced transient facial weakness, while retrograde dissection demonstrated a trend toward reduced transient weakness compared with antegrade. In malignant disease, outcomes were similar across approaches. Selective application of extracapsular and retrograde techniques may optimize facial nerve outcomes and operative efficiency.

Objective:Salivary adenoid cystic carcinoma (ACC) is a rare head and neck malignancy with limited surveillance guidelines. ACC disease patterns are quite variable and unpredictable. Herein, we present an institutional retrospective review of salivary adenoid cystic carcinoma and discuss patterns and predictors of recurrence. Study Design:Retrospective cohort study. Setting:Single Quaternary Care Referral Center. Methods:We analyzed 102 adult patients with salivary gland adenoid cystic carcinoma between 1988 and 2019. Patient and tumor-related characteristics are summarized, and recurrence, survival, and metastatic site data are described. Results:Multivariable analysis showed that greater than 30% solid pathology was independently predictive of recurrence (HR 5.32, CI 2.23-12.66). Advanced stage disease (stages III and IV) was also predictive of recurrence (HR 3.77, CI 1.57-9.03). Nearly one-third of all patients experienced distant recurrence. Among patients experiencing distant recurrence, 29% were diagnosed with distant recurrence more than 5 years post-treatment. Conclusion:These data support long-term surveillance and clinical follow-up for patients with ACC.

PURPOSE OF REVIEW:Graduated autonomy is a foundational principle of surgical education, yet no standardized framework exists for how autonomy should be structured, assessed, or achieved within head and neck oncologic and microvascular reconstructive fellowship training. This review examines contemporary models of graduated autonomy and integrates recent educational literature with institutional experience to explore competency development and training consistency. RECENT FINDINGS:Recent surgical education literature supports competency-based assessment and structured entrustment as central to operative autonomy progression. Supervisory trust decisions are increasingly recognized as multifactorial, incorporating technical skill, judgment, and procedural complexity rather than time-based advancement alone. In parallel, team-based operative models in head and neck oncologic and microvascular reconstructive surgery improve efficiency while maintaining oncologic and reconstructive outcomes, creating an environment conducive to progressive autonomy with consistent faculty oversight. SUMMARY:Graduated autonomy paired with structured assessment, individualized entrustment, and team-based operative workflows supports reliable development of technical proficiency and intraoperative judgment in fellowship training. Emerging literature and institutional experience suggest competency-based autonomy models can be implemented while preserving patient outcomes. Continued refinement and standardization of these frameworks are essential for advancement of fellowship education in head and neck oncologic and microvascular reconstructive surgery.

Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING-dependent CD8+ T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for cancer immunotherapy.

Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant challenge, with survival rates remaining poor despite advances in surgical technique and chemoradiation. While induction chemotherapy has historically failed to demonstrate a clear survival benefit, the emergence of neoadjuvant immunotherapy and chemoimmunotherapy has opened new avenues for investigation. There is now a rapidly growing focus on the potential for neoadjuvant chemoimmunotherapy to improve survival for locally advanced OCSCC. Moreover, neoadjuvant chemoimmunotherapy holds the potential to reduce preoperative tumor burden, potentially allowing for a response-adapted surgery that optimizes postoperative quality of life while maintaining oncologic safety. Despite these promising early findings, data are heterogeneous and randomized controlled trials are lacking. This narrative review provides an overview and interpretation of current data as it relates to the role of neoadjuvant chemotherapy and immunotherapy to improve survival and postoperative function for locally advanced OCSCC, highlighting the need for standardized protocols and additional trials.

OBJECTIVE:To compare the diagnostic accuracy and safety of ultrasound-guided fine needle aspiration (FNA) versus core needle biopsy (CNB) for parotid masses. STUDY DESIGN:Retrospective cohort study. SETTING:Tertiary academic medical center, 2018 to 2023. METHODS:We reviewed 485 patients undergoing ultrasound-guided parotid biopsy (426 FNAs and 59 CNBs). Permanent histopathology served as the reference standard. Primary outcomes included diagnostic performance metrics for neoplasm, malignancy, and tissue-specific diagnosis. Secondary outcomes included nondiagnostic rates, complications, time to surgery, and technical factors (needle gauge, biopsy setting, and number of passes). RESULTS:CNB demonstrated superior sensitivity (80.0% vs 54.9%, P = .032), accuracy (86.4% vs 68.5%, P = .007), and positive predictive value (87.0% vs 56.4%, P = .01) for detecting malignancy compared to FNA. CNB had superior tissue-specific accuracy (67.8% vs 49.5%, P = .009), particularly for squamous cell carcinoma and mucoepidermoid carcinoma. FNA had a higher nondiagnostic rate (20.0% vs 5.1%, P = .004). Greater CNB accuracy correlated with ≥3 needle passes and use of 17 to 18 gauge needles. Complication rates were low and similar (3.4% CNB vs 2.1% FNA), with no facial nerve injuries or tumor seeding reported. Time to surgery was comparable (CNB 51 days vs FNA 42 days, P = .10) in cases of malignancy. CONCLUSION:CNB showed improved diagnostic accuracy and fewer nondiagnostic results than FNA for parotid masses, particularly for suspected malignancies and complex histologies, without added risk or delay. CNB should be considered in cases suspicious for malignancy or where tissue-specific diagnosis would inform operative planning.

6056 Background: Lymphadenectomy remains a central component of definitive treatment for head and neck squamous cell carcinoma (HNSCC). However, lymphadenectomy disrupts the draining regional lymph node basin where anti-tumor immune cell priming can occur. We hypothesized that history of regional lymph node depletion may be associated with decreased efficacy of immune checkpoint blockade (ICB) in patients who suffer recurrent or metastatic (R/M) HNSCC. Methods: This was a single-institution retrospective cohort study including all patients treated with ICB (anti-PD-1 mAb) for R/M HNSCC from 2015 - 2025. Patients with distant metastatic disease at presentation were excluded. Demographic, clinicopathologic, and treatment history prior to ICB were collated and summarized for each patient. We defined regional lymph node depletion (LN depletion) as history (at any time prior to ICB initiation) of bilateral lymphadenectomy, > 4 levels dissected, or ≥18 lymph nodes excised. We then examined history of LN depletion as a predictor of ICB disease control rate (DCR: SD, PR, or CR) and progression-free survival (PFS) after ICB with Kaplan-Meier method and Cox models alone and controlling for tumor HPV status. Results: Our cohort was comprised of 100 patients (median age 72 years, 71% male). Primary tumor sites included oral cavity (n=38) p16+ oropharynx (n=23), larynx (n=21), p16- oropharynx (n=13) and sinonasal (n = 5). Forty-six were treated with first-line ICB, while 54 were treated after platinum chemotherapy failure. Sixty had a history of lymphadenectomy prior to ICB. Of these 60 patients, 51 (85%) had a history of radiation prior to ICB. History of regional LN depletion was significantly associated with lower DCR with ICB when considering bilateral lymphadenectomy (25.9% vs 54.8%, p = 0.03), > 4 levels dissected (25.0% vs. 54.8%, p = 0.02), or ≥18 lymph nodes excised (25.0% vs. 84.6%, p < 0.0001) analyzed alone and on bivariate analysis controlling for HPV status. In patients meeting all three criteria for LN depletion (n = 24), DCR was the lowest at 16% compared to 75% for patients meeting none of the criteria. On bivariate analyses controlling for HPV status, history of bilateral lymphadenectomy (HR: 2.04 [95% CI 1.1 – 3.8] p = 0.02), > 4 levels dissected (HR: 1.82 [95% CI: 1.0 – 3.3] p = 0.05, and ≥18 lymph nodes excised (HR: 3.35 [95% CI: 1.4 – 8.1] p < 0.01) were independently associated with poorer PFS after ICB. Conclusions: In patients with R/M HNSCC, prior regional LN depletion was associated with lower DCR and PFS after ICB. This suggests that greater surgical disruption of draining regional lymph node basins prior to ICB may affect immune response.

OBJECTIVE:Tracheoesophageal puncture (TEP) is the preferred method for voice rehabilitation following total laryngectomy (TL). In 2016, we described a novel method for in-office, secondary TEP with immediate prosthesis placement using a transnasal esophagoscope (TNE) and Seldinger technique. The present study provides an updated report on its utility and outcomes. METHODS:We performed a retrospective review of patients who underwent in-office secondary tracheoesophageal puncture with immediate prosthesis placement following total laryngectomy at our institution between 2012 and 2024. Procedural success, complications, and voice outcomes were assessed to evaluate the utility and safety of this technique. RESULTS:From 2012 to 2024, we used our technique for secondary TEP in 378 patients following TL with a 99.2% success rate. Patients had a median age of 63 (19-93) years and 82.3% were male (n = 311). The median time between TL and first TEP was 37 (7-6334) days. The majority of patients (93.4%) were able to voice immediately after voice prosthesis placement. Two patients (0.5%) developed pneumothorax post-procedure requiring admission and 2 procedures (0.5%) were aborted due to intolerance. No false passages, esophageal perforations, or bleeding complications encountered. CONCLUSION:Our technique for in-office secondary TEP via TNE and the Seldinger technique is feasible, effective, and well tolerated by patients.

BACKGROUND:Despite carrying significant complication risk, titanium plates remain the standard-of-care in the reconstruction of segmental mandibulectomy defects. Radiation therapy (RT) is known to impair wound healing and cause dose perturbation at the metal-tissue interface. In this study, we sought to investigate the relationship between RT dosimetry and hardware-related complications. METHODS:A retrospective review of 99 patients who underwent segmental mandibulectomy with osseous free flap and titanium plate reconstruction between 2013 and 2022 was performed. Multivariable logistic and linear regression were performed to evaluate hardware-related complications, including plate exposure, fracture, screw loosening, and fistula/infection, adjusting for age, tumor stage, diabetes, and tobacco history. RESULTS:Overall, 60 patients (60.6 %) experienced at least one plate-related complication at a median of 11.2 months (range 0.33-93.1 months) and mean of 22.1 ± 15.8 months from surgery. Plate removal was required in 28.3 % of the cohort. Each 1 Gy of radiation conferred a 6.8 % increase in the odds of any plate complication (OR 1.07, 95 % CI 1.00-1.14, P = 0.037), with > 60 Gy predicting any plate complication (OR 3.07, 95 % CI 1.12-8.41, P = 0.03), plate removal (OR 3.13, 95 % CI 1.15-8.53, P = 0.026) and fistula or soft tissue infection (OR 2.99, 95 % CI 1.13-7.87, P = 0.027) after controlling for age, tumor stage, diabetes, and tobacco use. CONCLUSIONS:Titanium reconstruction plates carry a high complication rate, with a threshold of > 60 Gy associated with a three-fold increase in complication risk. These findings suggest a need for alternative plating strategies or materials to reduce patient morbidity.

This cohort study examines the role of prior tonsillectomy in higher positive margins or worse survival among patients with human papillomavirus-associated tonsillar squamous cell carcinoma.

Head and neck lymphedema (HNL) is a common complication of head and neck cancer (HNC) treatment. Surgery and radiation, the backbones of HNC treatment, disrupt lymphatic networks through direct injury and fibrosis, leading to accumulation of lymphatic fluid in interstitial spaces. This causes swelling of external and internal structures, leading to decreased quality of life, cosmetic distress, social withdrawal, and functional deficits such as dysphagia, dysphonia, and reduced cervical mobility. In this narrative review, we provide a broad overview of the pathophysiology, assessment, and prevention of HNL. Key surgical factors include the extent of neck dissection, including specific levels removed. Radiation compounds surgical injury through lymphatic fibrosis in a dose-dependent manner. Emerging radiation de-escalation strategies may reduce HNL, though lymphedema is rarely studied as a trial endpoint. Moreover, assessment of HNL remains challenging due to the absence of a gold standard—patient-reported outcome measures, clinician-reported scales, and instrumental tests each capture distinct components of external and internal HNL. Currently, the cornerstone of HNL treatment is conservative management with complete decongestive therapy, which shows mixed efficacy and does not address internal HNL. Surgical options including lymphovenous anastomosis and vascularized lymph node transfer show early promise but remain limited to case reports and small series. Lymphatic imaging, particularly indocyanine green lymphography, represents a promising emerging modality for guiding personalized treatment planning, though application to the head and neck remains challenging. Ultimately, current management of HNL remains largely reactive, with a noticeable lack of preventative therapies. Future research may benefit from better defining surgical options, including HNL as an endpoint in radiation de-escalation trials, and validate emerging lymphatic imaging techniques in order to improve outcomes for HNC survivors.

e18120 Background: Comprehensive lymph node resection is a quality measure previously associated with survival for head and neck squamous cell carcinoma (HNSCC); however, the prognostic significance of nodal yield after neoadjuvant immunotherapy is an important unanswered question for clinical management and trial development. This study evaluated the association of lymph node yield with overall survival (OS) among patients with HNSCC who underwent neoadjuvant immunotherapy. Methods: The US National Cancer Database (2004-2022) was queried for HNSCC patients who underwent neoadjuvant immunotherapy followed by surgical resection. 1:1 matched non-neoadjuvant controls were created using demographic variables, facility, stage, lymphovascular invasion, and year. Positive lymph node percentage (malignant lymph nodes/total lymph nodes resected) was assessed. Cox proportional hazard models identified prognosticators of five-year OS. Results: The study included 462 patients who received neoadjuvant immunotherapy and 462 matched controls. Median age was 60 years [IQR 53-67] and 74.5% were male. The majority (53.5%) had stage IV disease and received adjuvant radiation (72.7%). Compared to non-neoadjuvant controls, those who received neoadjuvant immunotherapy had more lymph nodes (median [IQR] 43 [31-60] vs 29 [18-45] P<0.001), but a similar percentage of positive nodes (2.5% [0.0%-7.1%] vs 3.1% [0.0%-8.8%], P=0.09). Total number of nodes removed did not predict survival in the neoadjuvant immunotherapy group. Positive lymph node percentage predicted 5-year OS, with every one-percent increase in positive lymph nodes resulting in increased hazard of death by 1.4% (HR: 1.014, 95% CI: 1.006, 1.023) and 1.6% (HR: 1.016, 95% CI: 1.010, 1.030) in unadjusted and adjusted models, respectively. Conclusions: In patients with head and neck cancer treated with neoadjuvant immunotherapy, lymph node yield is not associated with improved survival. Prospective studies are required to determine if typical quality metrics for lymph node yield apply to patients treated with neoadjuvant immunotherapy.

As rates of human papillomavirus-positive (HPV+) oropharynx cancer increase, there is increasing need for accurate biomarkers for diagnosis, treatment, and surveillance. The analytical performance of MyHPVscore, a droplet digital PCR laboratory-developed test, was characterized to detect circulating tumor DNA from multiple high-risk HPV (hrHPV) types (16, 18, 31, 33, 35, and 39) in plasma from patients with HPV+cancer. Using Clinical and Laboratory Standards Institute guidelines, MyHPVscore was developed and validated in a Clinical Laboratory Improvement Amendments-certified laboratory. Analytical controls and plasma samples from patients with HPV+oropharyngeal squamous cell carcinoma and noncancer controls were used to evaluate sensitivity, specificity, linearity, and analyte stability. MyHPVscore demonstrated high analytical performance for detecting multiple hrHPV types. Limits of blank were 2.7 (HPV16) and 2.6 (other hrHPV types) positive droplets/reaction; limits of detection were 15.2 and 20.8 positive droplets/reaction, respectively. The linear range was 15 to 62,500 targets/mL plasma (HPV16) and 12 to 100,000 targets/mL (other hrHPV types) with strong correlation (R2 > 0.99). Analytes were stable for 96 hours at -20°C and yielded consistent qualitative results after >400 days of storage. No cross-reactivity was observed between hrHPV types or low-risk types (HPV6 and HPV11). These results support the use of MyHPVscore as a laboratory-developed test for detecting HPV+oropharynx cancer. This method establishes an approach and standard controls that can benchmark other emerging circulating tumor DNA assays.

Objectives:Primary neuroendocrine carcinoma (NEC) of the head and neck is rare (< 1% of cases) and aggressive, with poorly defined management strategies. This study evaluated clinical characteristics, treatment patterns, and survival outcomes in a single-institution cohort, identifying factors associated with improved survival. Methods:A retrospective review was conducted of patients with head and neck NEC treated at a tertiary center. Variables associated with 3-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed using Cox regression and Kaplan-Meier curve analyses. Results:Sixty-nine patients (59.4% male, 95.7% White) were included. The most common subsites were sinonasal (36.2%) and laryngeal (30.4%). Most tumors were poorly differentiated (73.9%), and 50.7% were T category 3-4. Surgical resection was performed in 68.1% and primary radiotherapy or chemoradiotherapy in 20.3% of patients. Overall 3-year OS and RFS were 55.5% and 56.1%, respectively. On multivariable analysis, surgery remained associated with improved 3-year OS (adjusted hazard ratio [aHR]: 0.21, 95% CI: 0.06-0.66, p = 0.007) and DSS (aHR: 0.33, 95% CI: 0.11-0.99, p = 0.050) when controlling for tumor stage, histologic differentiation, tumor site, and age at diagnosis. Chemotherapy and radiotherapy were not associated with survival. Conclusions:Head and neck NEC carries a poor prognosis. Undergoing surgical resection was strongly associated with improved 3-year OS and DSS in our cohort, highlighting its importance when feasible. Multicenter collaboration and prospective studies are warranted to refine optimal treatment strategies for this rare and challenging malignancy.

Supplementary Figure from Impact of Nodal Metastases in HPV-Negative Oropharyngeal Cancer

OBJECTIVE:We assessed correlations between tumor carbonic anhydrase IX (CAIX) staining, as a marker of tumor hypoxia, and CD8+ T-cell infiltration in a cohort of patients with advanced laryngeal squamous cell carcinoma undergoing a bioselection approach for definitive treatment. STUDY DESIGN:Retrospective cohort study. SETTING:Tertiary care hospital. METHODS:Patients with stage III to IV laryngeal squamous cell carcinoma treated under a bioselection paradigm were included. Immunohistochemistry for CD8+ T-cells and CAIX was performed. Nonparametric tests and Kaplan-Meier survival analyses were used to compare tumor CAIX status by clinicopathologic variables and CD8+ T-cell infiltration and to evaluate the role of CAIX and combination CAIX/tumor infiltrating lymphocytes (TIL) category on survival. RESULTS:Our cohort included 92 patients (n = 68 [73.9%] supraglottic). No difference in CAIX staining was seen by tumor subsite, stage, and response to induction chemotherapy (all P > .05). Thirteen (14.1%) tumors were CAIX-positive and showed significantly lower CD8+ T-cell infiltration than CAIX-negative tumors (18 [0-62] vs 32 [0-399], P = .028). Combination CAIX/TIL category was significantly associated with the likelihood of response (CAIX-/TIL[high] were less likely to respond) and in the group of responders, was predictive of a higher degree of tumor shrinkage (>80%). CONCLUSION:CAIX staining correlates with reduced CD8+ T-cell infiltration in patients with advanced laryngeal squamous cell carcinoma undergoing bioselection. The combination CAIX/TIL category is associated with the likelihood and degree of response to induction. The utility of CAIX status and other combination immune and hypoxia signatures as a biomarker of induction response and survival merits prospective evaluation.

Odds ratios (OR) and p values for multi-variable models for acute and late toxicity outcomes including covariates of p16+ OPSCC vs LAHNSCC, primary tumor volume (GTVp) and RT boost volume treated.