Examining timing of periorbital interventions in patients with upper division facial paralysis.

BACKGROUND: Facial paralysis is a life-altering condition that may arise from various etiologies, ranging from trauma to malignancy. Permanent facial paralysis may occur secondary to facial nerve sacrifice or irreversible damage to the nerve. In these particularly devastating cases, protection and maintaining function of the eye is paramount. There are many effective lagophthalmos corrective surgical procedures available for these patients. While placement of eyelid weights and lid tightening surgeries are the cornerstone of eyelid rehabilitation, limited information exists on whether the timing of eyelid interventions in the setting of permanent facial paralysis impact outcomes, including need for revision surgery. METHODS: A single-center retrospective chart review was performed for patients with irreversible facial paralysis treated with an upper eyelid weight between 2013 to 2022. Electronic health records were acquired to obtain facial paralysis etiology, associated clinical characteristics, the type of intervention, and the timing of intervention. Patients were classified as immediate if the eyelid weight operation occurred within 29 days of the initial facial paralysis and delayed if the surgery occurred 30 days or more after initial presentation. Outcomes were assessed in terms of revision procedures and surgical complications. RESULTS: There were 70 patients in total, with 35 patients in the immediate category and 35 patients in the delayed category. The most common etiology related to parotid gland pathology, and 58.6% of patients had facial paralysis from cancer-related surgeries. There were no significant differences in revision rates (p < 0.208) or in the types of procedures (p = 0.077) between the two groups. The complication rates also did not differ significantly between groups; however, there were only complications in the delayed intervention group. CONCLUSIONS: These findings suggest there is no difference in postoperative complications between groups, including the need for revision surgeries when comparing groups with immediate or delayed intervention. Thus, treatment plans should be customized based on patient and provider preferences.

Role of 18F-FDG PET/CT in the management of head and neck cancer patients with persistent cervical lymphadenopathy following chemoradiation.

BACKGROUND: We aim to describe the management and outcomes of patients with persistent lymphadenopathy (LAD) after primary chemoradiation for head and neck squamous cell carcinoma (HNSCC) based on post-treatment PET/CT results. METHODS: Retrospective chart review was conducted of all patients who underwent primary concurrent chemoradiation for HNSCC at a tertiary care center from 2010 to 2022 and had persistent post-treatment LAD. RESULTS: Nearly 62% of patients were managed conservatively, and 27.0% underwent neck dissection. PET-positive patients were more likely to undergo neck dissection than PET-negative patients (p = 0.042). Positive predictive value (PPV) and negative predictive values (NPV) of PET/CT in detecting residual disease in the neck were 48.0% and 73.7%, respectively. CONCLUSIONS: PPV and NPV of PET/CT for detecting residual neck disease in patients with post-treatment LAD was lower than those of HNSCC patients with and without persistent LAD reported in other studies.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Development of hypothyroidism following hemithyroidectomy: A population-based study.

PURPOSE: Hypothyroidism is a known possibility after hemithyroidectomy, with a highly variable incidence in the literature ranging from 8 to 60 %. Incidence of hypothyroidism after hemithyroidectomy was evaluated with a secondary aim to assess incidence in patients with Hashimoto's disease. MATERIALS & METHODS: A retrospective study using the TriNetX global federated research network was performed. We included patients within the last 15 years that were ≥18 years of age and had Current Procedural Terminology codes for hemithyroidectomy. Patients were excluded if they had a total or completion thyroidectomy at any time, a history of thyroid cancer, were preoperatively either on levothyroxine, diagnosed with hypothyroidism, or had a Thyroid Stimulating Hormone ≥ 4 m[IU]/L. We assessed the 3 month incidence of hypothyroidism postoperatively based on the International Classification of Diseases code, TSH ≥ 4 m[IU]/L, or taking levothyroxine after surgery. RESULTS: 6845 patients met the inclusion criteria. Most of the cohort was female (67 %) and white (63 %). The mean age at surgery for this population was 54 ± 14.8 years. During the 15 years of data, we found the 3-month incidence of hypothyroidism following hemithyroidectomy to be 23.58 %. The median time to develop the disease was 41.8 months. A subgroup analysis of those with Hashimoto's revealed a 3-month incidence of 31.1 % of patients developing hypothyroidism after surgery. CONCLUSIONS: This population-based study gives additional insight into the incidence of hypothyroidism after hemithyroidectomy. This will help improve perioperative patient counseling and management.

Beta-defensin index: A functional biomarker for oral cancer detection.

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.

Assessing the Association Between Head and Neck Cancer and Granulomatosis with Polyangiitis.

Objective: To determine the odds of head and neck cancer (HNC) in patients with a concurrent or prior diagnosis of granulomatosis with polyangiitis (GPA). Methods and Materials: The TriNetX Analytics Network, a federated research platform that aggregates de-identified electronic health record data of over 130 million patients worldwide, was queried for patients with at least one ICD-10 encounter diagnosis of GPA. Patients within this group with an encounter diagnosis of cancer of the sinonasal, oral cavity, oropharynx, nasopharynx, and larynx concurrent or after the initial encounter diagnosis of GPA were recorded and compared to a standardized control population to determine odds ratios with a 95% confidence interval (CI). Relevant confounding variables, including human papillomavirus, Epstein Barr virus, tobacco, and alcohol exposure, were balanced between cohorts by 1:1 propensity matching. Results: Of the patients in the GPA cohort, 126 (0.48%) had an ICD-10 diagnosis of HNC. When stratifying by head and neck subsites, 20 (0.08%), 18 (0.07%), 23 (0.09%), 70 (0.27%), and 22 (0.084%) GPA patients had an ICD-10 encounter diagnosis of cancer involving the sinonasal, nasopharynx, larynx, oral cavity, and oropharynx. When comparing the experimental GPA group with the standardized control population after matching, patients in the GPA group had 1.3 times (95% CI: 1.03-1.175) greater odds of HNC when including cases diagnosed after or concurrently with the diagnosis of the vasculitis. There was no statistical difference in the odds of cancer at each anatomical subsite between the GPA and control cohort after matching. Conclusion: Our study identifies a statistically significant increase in the odds of HNC encounter diagnoses in patients with GPA.

Is sentinel lymph node biopsy needed for lentigo maligna melanoma?

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases. METHODS: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status. RESULTS: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05). CONCLUSION: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines.

Prognostic significance of time trends in treatment of head and neck squamous cell carcinoma.

PURPOSE: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS). STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI. RESULTS: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Cox-regressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival. CONCLUSIONS: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.

Loss to Follow-up in Head and Neck Cancer: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To evaluate the reporting and rates of loss to follow-up (LTFU) in head and neck cancer (HNC) randomized controlled trials based in the United States. DATA SOURCES: Pubmed/MEDLINE, Cochrane, Scopus databases. REVIEW METHODS: A systematic review of titles in Pubmed/MEDLINE, Scopus, and Cochrane Library was performed. Inclusion criteria were US-based randomized controlled trials focused on the diagnosis, treatment, or prevention of HNC. Retrospective analyses and pilot studies were excluded. The mean age, patients randomized, publication details, trial sites, funding, and LTFU data were recorded. Reporting of participants through each stage of the trial was documented. Binary logistic regression was performed to evaluate associations between study characteristics and reporting LTFU. RESULTS: A total of 3255 titles were reviewed. Of these, 128 studies met the inclusion criteria for analysis. A total of 22,016 patients were randomized. The mean age of participants was 58.6 years. Overall, 35 studies (27.3%) reported LTFU, and the mean LTFU rate was 4.37%. With the exception of 2 statistical outliers, study characteristics including publication year, number of trial sites, journal discipline, funding source, and intervention type did not predict the odds of reporting LTFU. Compared to 95% of trials reporting participants at eligibility and 100% reporting randomization, only 47% and 57% reported on withdrawal and details of the analysis, respectively. CONCLUSION: The majority of clinical trials in HNC in the United States do not report LTFU, which inhibits the evaluation of attrition bias that may impact the interpretation of significant findings. Standardized reporting is needed to evaluate the generalizability of trial results to clinical practice.

Incidence and medical complications of COVID-19 in the total laryngectomy population: A population-based study.

OBJECTIVES: Laryngeal and hypopharyngeal cancers treated with total laryngectomy (TL) may provide a unique avenue for COVID-19 to infect cancer patients. The objective of this investigation was to identify incidence of COVID-19 infection and potential complications in TL patients. MATERIALS AND METHODS: Data was extracted from TriNetX COVID-19 research network from from 2019 to 2021 and ICD-10 codes were utilized to query for laryngeal or hypopharyngeal cancer, and outcomes of interest. Cohorts were propensity score-matched based on demographics and co-morbidities. RESULTS: A query of active patients in TriNetX from January 1, 2019 to December 31, 2021 identified 36,414 patients with laryngeal or hypopharyngeal cancer out of the 50,474,648 active patients in the database. The overall COVID-19 incidence in the non-laryngeal or hypopharyngeal cancer population was 10.8% compared to 18.8% (p < 0.001) in the laryngeal and hypopharyngeal cancer group. Those who underwent TL had a statistically significant increased incidence of acquiring COVID-19 (24.0%) when compared to those without TL (17.7%) (p < 0.001). TL patients with COVID-19 had a higher risk of developing pneumonia RR (risk ratio) 1.80 (1.43, 2.26), death 1.74 (1.41, 2.14), ARDS 2.42 (1.16, 5.05), sepsis 1.77 (1.37, 2.29), shock 2.81 (1.88, 4.18), respiratory failure 2.34 (1.90, 2.88), and malnutrition 2.46 (2.01, 3.01) when matched with those COVID-19 positive cancer patients without TL. CONCLUSIONS: Laryngeal and hypopharyngeal cancer patients had a higher rate of acquiring COVID-19 than patients without these cancers. TL patients have a higher rate of COVID-19 compared to those without TL and may be at a higher risk for sequalae of COVID-19.

Job market in head and neck surgery: A survey and analysis of recent fellowship graduates.

OBJECTIVE: Recent years have seen increase in individuals pursuing postgraduate fellowships in head and neck (HN) surgery. This has presented concerns about insufficient jobs where graduates can apply their scope of specialized training. METHODS: Data was collected in two manners- a survey and a manual online search of American Head and Neck Society (AHNS) fellowship graduates. A 25-question survey was sent in 2021 to approximately 400 HN fellows who graduated between 2010 and 2020. The AHNS list of graduates from the same years were searched online to collect information including gender, graduation year, fellowship training, and current job practice. RESULTS: Of the 78 survey responses, 64.1 % were male and 34.6 % female. 96.2 % reported ablative, 84.6 % microvascular, and 82.1 % TORS training. Mean number of interviews was 4 with most interviewing during the 3rd quarter (January to March). Majority reported being in academic and university-based practices (79.6 %). Online search was done on 393 graduates. Since 2010 the number of graduates almost doubled. There was a statistically significant increase in females by year (p = 0.022). There was a significant decrease (p = 0.022) in graduates with additional fellowship training from that of their AHNS fellowship. There was also a statistically significant increase in graduates being in academic practices (p = 0.022). CONCLUSION: Despite growing numbers, there appears to be more graduates entering an academic practice, although the definition of an academic HN practice may be evolving. These results provide guidance on how to approach the job search in a select market. LEVEL OF EVIDENCE: II.

Treatment failure patterns are similar between p16- and p16+ oropharyngeal squamous cell carcinomas.

Background: The incidence of p16+ oropharyngeal squamous cell carcinoma (OPSCC) has been increasing. The notion that p16+ OPSCC has a propensity for atypical and disseminating metastasis has gained traction. We compared treatment failure patterns in p16+ and p16- OPSCC and evaluated survival impact. Methods: Retrospective analysis of patients with recurrent/metastatic OPSCC disease between 1/2009 and 12/2019. Results: Thirty-eight p16+ and 36 p16- patients were identified. Three distinct failure patterns (distant vs. locoregional, atypical vs. typical, and disseminating vs. non-disseminating) were studied. No significant differences were found between p16+ and p16- patients. Multivariate analysis showed p16 status was an independent prognostic biomarker; p16+ patients have a favorable overall survival compared to p16- patients (HR 0.34, 95% CI 0.16-0.77; P = .005). Conclusions: We challenge the view that p16+ OPSCC exhibits a distinctive treatment failure pattern and showed that p16 status impacts patient survival independent of disease progression.

The impact of microscopic versus macroscopic extranodal extension in oral cavity squamous cell carcinoma: National cancer database analysis and review of the literature.

OBJECTIVE: To analyze the prognostic significance of microscopic vs macroscopic extranodal extension and to assess the impact of chemoradiation on overall survival among patients with oral cavity squamous cell carcinoma and varying degrees of extranodal extension. METHODS: Utilizing the National Cancer Database, we performed a retrospective cohort study of 7975 patients with oral cavity squamous cell carcinoma and varying degrees of extranodal extension who underwent primary surgical intervention. Propensity-score matched models following Cox regression analyses allowed us to assess the impact of adjuvant radiation alone vs adjuvant chemoradiation on overall survival in patients with microscopic extranodal extension and macroscopic extranodal extension. RESULTS: 7975 patients with oral cavity squamous cell carcinoma were included in the final analysis. Within this cohort, 25.4% had microscopic extranodal extension and 5.2% had macroscopic extranodal extension. On univariate analysis, we found that microscopic and macroscopic extranodal extension were associated with decreased overall survival when compared to those with positive nodes without extranodal extension (HR = 1.67; 95% CI 1.56, 1.79 and HR = 1.88; 95% CI 1.66, 2.14, respectively). On multivariate analysis after propensity-score matching, we found no significant difference in overall survival in patients who received adjuvant radiation alone vs. adjuvant chemoradiation for both microscopic and macroscopic extranodal extension. CONCLUSION: Our data suggest that microscopic extranodal extension in oral cavity squamous cell carcinoma is associated with worse overall survival than patients without extranodal extension following primary surgical intervention with neck dissection. The results of this study also suggest that the addition of chemotherapy to adjuvant radiation may not provide a significant survival benefit in patients with oral cavity squamous cell carcinoma with microscopic and macroscopic extranodal extension. Comprehensive assessment of the benefits of adjuvant chemoradiation in the setting of microscopic vs macroscopic extranodal extension would need to be studied in a randomized controlled trial.

Impact of AJCC 8th edition staging system and definitive treatment choice on the prognosis of complete responders with p16+ and p16- oropharyngeal squamous cell carcinomas.

OBJECTIVES: To identify predictors of overall survival (OS) in oropharyngeal squamous cell carcinoma (OPSCC) patients who achieved complete response (CR). METHODS: We performed a retrospective study of OPSCC patients who achieved CR from a single academic medical center. Associations between OS, AJCC 8th edition staging system, definitive treatment choice, smoking history, and p16 status were assessed. RESULTS: p16+ status was associated with favorable prognosis for CR (p < 0.001) but not non-CR (p = 0.67) patients. For early stage, p16+ OPSCC patients who achieved CR, surgery + adjuvant radiation (RT) treatment was more durable compared to concurrent chemoradiation (CRT), particularly in smokers. CONCLUSIONS: Curative intent treatment choice and smoking history has an impact on the long-term OS of the CR p16+ OPSCC cohort. Prospective studies to define the optimal multi-modality treatment option to manage p16+ OPSCC patients is needed.

Impact of intraoperative ischemia time on acute complications of head and neck microvascular free tissue transfer: A systematic review and meta-analysis.

BACKGROUND: To evaluate the relationship between intraoperative ischemia time with acute microvascular free tissue transfer (MFTT) complications in head and neck reconstruction. METHODS: A systematic review using PRISMA guidelines was performed. Inclusion encompassed all available studies published and indexed using PubMed, Medline, and Embase. Meta-analyses were performed using the Cochrane Review Manager tool. Methodological Index for Non-Randomized Studies (MINORS), the Revised Cochrane risk-of-bias tool for randomized trials, and the NIH Study Quality Assessment Tool for non-randomized prospective studies. RESULTS: A total of 430 citations were reviewed. 25 were included in our overall qualitative analysis, and 14 for meta-analysis. When comparing ischemia times for flaps with and without complications, no significant difference was observed (p = 0.98). Additionally, in a separate cohort, no significant effect was realized when correlating ischemia time to overall rates and total complications. CONCLUSION: Ischemia time was not significantly different between those with and without acute flap complications.

Occult nodal metastasis in major salivary gland malignancy: An update from the National Cancer Database.

OBJECTIVES: Malignant salivary gland tumors are rare neoplasms that are vastly heterogenous in their histological patterns and clinical behaviors. As a consequence, studies have lacked the robust sample sizes needed to define treatment strategies. In this study, we used the National Cancer Database to identify the incidence of occult nodal metastasis and effect on overall survival for the most common malignant salivary gland subtypes. A retrospective review of patients in the National Cancer Database with primary site malignancies of major salivary glands between 2004 and 2016 was performed. Subjects included in the study underwent surgical treatment with and without adjuvant radiation and had complete information on TNM pathological stage. MATERIALS AND METHODS: 8,689 patients with primary malignant salivary gland cancer were analyzed. The sample was stratified by histologic subtype. Univariate analysis of lymph node metastasis of the whole cohort showed a higher risk of death (p < 0.001), when compared to those without. Also when comparing occult vs evident metastasis, the risk of death was higher for the latter (p < 0.001). RESULTS AND CONCLUSION: Occult cervical lymph node metastasis ranged from 14.9% to 35.8% in malignant salivary gland cancers, depending on histological subtype. Occult nodal metastasis was a poor prognostic factor with significantly worse overall survival.

Incidence of synchronous malignancies found during triple endoscopy in head and neck cancer.

OBJECTIVES: To investigate the incidence of synchronous malignancies identified during triple endoscopy in patients with head and neck squamous cell carcinoma. METHODS: A retrospective chart review of patients from a tertiary academic medical center was performed. Patients with a primary head and neck squamous cell carcinoma who underwent triple endoscopy were included. Operative, radiographic, and pathology reports were reviewed to evaluate for the presence of synchronous malignancies in the aerodigestive tract diagnosed through endoscopy. Demographics, relevant medical history, including tobacco and alcohol use, and tumor characteristics were recorded. Univariate and multivariate regression analyses were conducted to assess for associations with synchronous malignancy on triple endoscopy. RESULTS: 215 patients were reviewed, 164 of which had a biopsy-positive head and neck squamous cell carcinoma and underwent triple endoscopy. Synchronous lesions were found in 8 patients (4.9%). Of the synchronous lesions, only two were identified on esophagoscopy and bronchoscopy; the remaining six were found on direct laryngoscopy. Clinical comorbidities including smoking and alcohol history, tumor p16 status, and tumor stage were not associated with presence of synchronous lesions. A positive synchronous lesion on positron emission tomography was significantly correlated with finding a synchronous lesion on triple endoscopy (p = 0.006). CONCLUSION: This study shows the incidence of synchronous lesions on triple endoscopy to be closer to 5%. While endoscopic examination can be useful in the anatomic characterization of head and neck malignancies, the low incidence of synchronous malignancies suggests that the need for triple endoscopy may be considered on a case-by-case basis.

Impact of p16 Status and Anatomical Site in Anti-PD-1 Immunotherapy-Treated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Patients.

In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23-47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized.