International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

BACKGROUND: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. METHODS: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. RESULTS: After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. CONCLUSIONS: Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.

Pediatric Robotic Laryngeal Cleft Repair.

OBJECTIVE: Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. METHODS: Pediatric patients who underwent robotic or traditional (open or endoscopic) LC repair between 2010 and 2021 were identified. Patient characteristics, operative times, adverse events, hospital length of stay (LOS), and modified barium swallow study (MBSS) results were compared. RESULTS: Eighteen robotic and thirty traditional LC repairs were identified. Mean surgical (149 vs 111 min, P < .05) and OR times (207 vs 139 min, P < .002) were increased for robotic type I LC repairs, but were similar for type II and III LC. Mean hospital LOS was increased for robotic type I LC repairs (2.6 vs 1.2 days, P < .006), but was decreased for type II (4 vs 12.2 days) and type III (4.3 vs 94.5 days) LC. Postoperative MBSS results were improved for robotic type I LC repairs at 12 months (82% vs 43%, P = .05), and trended toward improvement at 6 months for type II (75% vs 22%), and type III (67% vs 50%) LC repairs, although significance was limited for type II and III LC due to the number of subjects. A robotic approach was used successfully to revise all recurrent LC that failed traditional repairs. CONCLUSION: Robotic type 1 LC repairs demonstrated increased operative times and hospital LOS but improved postoperative swallow outcomes compared to traditional approaches may be particularly useful in cases of recurrent clefts.

Post-surgical readmission risk factors in otolaryngology/head and neck surgery.

BACKGROUND: Otolaryngology patients are a high-readmission-risk group due to the complexity of surgeries, significant alterations to speech and swallowing functions, and high postoperative complications risk. METHODS: A retrospective review was performed on patients who underwent otolaryngologic surgery at a single-academic-institution between March 2019 and February 2020. RESULTS: Among 365 discharges, 21 patients had unplanned readmissions within 30 days. On univariable analysis, acute myocardial infarction, number of total comorbidities, prior chemotherapy/radiation, active smoking, airway surgery, and enteral feeding, and on multivariable analysis, prior chemotherapy/radiation and active smoking were identified as significant readmission risk factors. Readmission risk increased from 2.43% to 7.48% and 41.67% with the addition of each risk factor. CONCLUSION: Nearly 75% of the readmissions were due to potentially preventable reasons. By identifying and proactively intervening on "at risk" patients during the perioperative timeframe, complications and readmission can be reduced, thereby improving the overall quality of care delivered.

The Toxicological Effects of e-Cigarette Use in the Upper Airway: A Scoping Review.

OBJECTIVE: While evidence continues to emerge on the negative health effects of electronic cigarettes (e-cigarettes) on the lungs, little is known regarding their deleterious effects on the upper airway. The purpose of this review is to summarize the toxicological effects of e-cigarettes, and their components, on the upper airway. DATA SOURCES: PubMed, SCOPUS, EMBASE databases. REVIEW METHODS: Systematic searches were performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from 2003 to 2023. Studies were included if they investigated the toxicological effects of e-cigarette exposure on human or animal upper airway tissue. Two authors independently screened, reviewed, and appraised all included articles. RESULTS: A total of 822 unique articles were identified, of which 53 met inclusion criteria and spanned subsites including the oral cavity (22/53 studies), nasal cavity/nasopharynx (13/53), multiple sites (10/53), larynx (5/53), trachea (2/53), and oropharynx (1/53). The most commonly observed consequences of e-cigarette use on the upper airway included: proinflammatory (15/53 studies), histological (13/53), cytotoxicity (11/53), genotoxicity (11/53), and procarcinogenic (6/53). E-cigarette humectants independently induced toxicity at multiple upper airway subsites, however, effects were generally amplified when flavoring(s) and/or nicotine were added. Across almost all studies, exposure to cigarette smoke exhibited increased toxicity in the upper airway compared with exposure to e-cigarette vapor. CONCLUSION: Current data suggest that while e-cigarettes are generally less harmful than traditional cigarettes, they possess a distinct toxicological profile that is enhanced upon the addition of flavoring(s) and/or nicotine. Future investigations into underexamined subsites, such as the oropharynx and hypopharynx, are needed to comprehensively understand the effects of e-cigarettes on the upper airway.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.

Implementation and Outcomes of ERAS Protocol for Major Oncologic Head and Neck Surgery.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols have been developed and successfully implemented for many surgical specialties, demonstrating reductions in length of stay, post-operative complications, and resource utilization. Currently, there are few documented applications of ERAS protocols in head and neck surgery. Additional description of head and neck surgery protocol design, implementation, and outcomes will help advance postoperative care. METHODS: An ERAS protocol was designed for patients undergoing glossectomy and primary or salvage laryngectomy with or without free flap reconstruction. Following successful protocol implementation, patient outcomes and perioperative metrics were retrospectively reviewed and compared between patients prior to and following the ERAS protocol. RESULTS: Global comparison of ERAS and control group did not show statistically significant differences in measured perioperative outcomes. There were no statistically significant differences between the ERAS and control groups in age, sex, BMI, surgery type, or cancer stage. The ERAS protocol was associated with reduced variability in hospital length of stay (LOS), demonstrated through tighter interquartile ranges. For patients undergoing salvage laryngectomy, the ERAS protocol was associated with a significant reduction in 30-day readmission rates. Although not statistically significant, the median length of stay in the step-down unit (ISCU) and hospital was lower for specific patient groups. CONCLUSION: The implementation and evaluation of the ERAS protocol demonstrated improvement in select patient outcomes as well as areas for process improvement. This study demonstrates the insights that arise from review of this protocol even for an institution with perceived standardized procedures for major oncologic head and neck surgeries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:732-740, 2024.

Effect of distance of treatment center on survival for HPV-negative head and neck cancer patients.

BACKGROUND: In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. METHODS: Patients with HPV-negative HNSCC were retrospectively identified from a statewide, population-based study. Euclidian distance from the home address to the treatment center was calculated for radiation therapy, surgery, and chemotherapy. Multivariable Cox proportional hazards models were used to examine the risk of 5-year mortality with increasing travel quartiles. RESULTS: There were 936 patients with HPV-negative HNSCC with a mean age of 60. Patients traveled a median distance of 10.2, 11.1, and 10.9 miles to receive radiation therapy, surgery, and chemotherapy, respectively. Patients in the fourth distance quartile were more likely to live in a rural location (p < 0.001) and receive treatment at an academic hospital (p < 0.001). Adjusted overall survival (OS) improved proportionally to distance traveled, with improved OS remaining significant for patients who traveled the furthest for care (third and fourth quartile by distance). Relative to patients in the first quartile, patients in the fourth had a reduced risk of mortality with radiation (HR 0.59, 95% CI 0.42-0.83; p = 0.002), surgery (HR 0.47, 95% CI 0.30-0.75; p = 0.001), and chemotherapy (HR 0.56, 95% CI 0.35-0.91; p = 0.020). CONCLUSION: For patients in this population-based cohort, those traveling greater distances for treatment of HPV-negative HNSCC had improved OS. This analysis suggests that the benefits of coordinated, multidisciplinary care may outweigh the barriers of travel burden for these patients.

Time to treatment patterns of head and neck cancer patients before and during the Covid-19 pandemic.

OBJECTIVES: The delivery of healthcare has changed significantly over the past decades. This study analyzes the clinicodemographic factors and treatment patterns of head and neck squamous cell carcinoma (HNSCC) patients between 2004 and 2020. MATERIALS AND METHODS: Retrospective cohort analysis of HNSCC patients from the National Cancer Data Base from 2004 to 2020. RESULTS: A total of 164,290 patients were included. Increased times from diagnosis to definitive surgery (TTS) were seen across all facility types (academic centers, AC; non-academic centers, NAC) between 2004 and 2019, with NAC affected more. TTS < 15 days (RR = 1.05, 95%CI:1.05-1.09) and > 75 days (1.07, 95%CI:1.05-1.09) were associated with increased mortality risk. This association was more prominent among HPV + HNSCC (RR = 1.45; 95%CI:1.18-1.78). Treatment in AC was associated with a decreased mortality risk (RR = 0.94, 95%CI:0.93-0.95). Despite the universal increase in wait times from 2004 to 2019, short-term mortality was significantly decreased from 2016 to 2019, relative to 2004-2007 (3-month mortality: RR = 0.77, 95%CI:0.70-0.85; 12-month mortality: RR = 0.80, 95%CI:0.77-0.84). Wait times decreased in 2020. CONCLUSIONS: TTS increased between 2004 and 2019, with NAC affected more. However, despite longer wait times, short-term survival increased significantly. Very short (<15 days) and very long (>75 days) TTS were associated with increased mortality risk. Patients with HPV + HNSCC have the highest increase among those treated > 75 days from diagnosis. Treatment at AC was associated with improved survival, which could be explained by the presence of multidisciplinary teams and subspecialists that may be less available at NAC. The 2021 NCDB data are required for a comprehensive analysis of wait times in 2020.

A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established. METHODS: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC. The primary end point was a hypothesized pathologic complete response rate of 50%. After chemo-immunotherapy and surgical resection, patients received study-defined, pathologic risk adapted adjuvant therapy consisting of either durvalumab alone (low risk), involved field radiation plus weekly cisplatin and durvalumab (intermediate risk), or standard chemoradiation plus durvalumab (high risk). RESULTS: Between December 2017 and November 2021, 39 subjects were enrolled at three centers. Oral cavity was the most common primary site (69%). A total of 35 of 39 subjects underwent planned surgical resection; one subject had a delay in surgery due to treatment-related toxicity. The most common treatment-related adverse events were cytopenias, fatigue, and nausea. Post treatment imaging demonstrated an objective response rate of 57%. Pathologic complete response and major pathologic response were achieved in 29% and 49% of subjects who underwent planned surgery, respectively. The 1-year progression-free survival was 83.8% (95% confidence interval, 67.4%-92.4%). CONCLUSIONS: Neoadjuvant carboplatin, nab-paclitaxel, and durvalumab before surgical resection of HNSCC were safe and feasible. Although the primary end point was not met, encouraging rates of pathologic complete response and clinical to pathologic downstaging were observed.

Diagnostic accuracy of FNA to determine HPV status in HPV-associated oropharyngeal squamous cell carcinoma.

PURPOSE/OBJECTIVE(S): Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. METHODS: Pathology samples from consecutive patients with pathologically confirmed HPV-associated OPSCC who underwent FNA of a cervical lymph node during initial diagnostic work-up were retrospectively analyzed between November 2015 and August 2021. RESULTS: Initial FNA was diagnostic for malignancy in 109/148 (73.6%) patients and non-diagnostic in 39/148 (26.4%). P16 staining of FNAs positive for malignancy showed: 54/109 (49.5%) p16 positive, 6/109 (5.5%) p16 negative, 49/109 (45.0%) p16 indeterminate. In patients with an initial non-diagnostic sampling or p16 indeterminate, repeat FNA was performed in 30/88 (34.1%) patients. Of the 30 repeat FNAs: 23/30 (76.7%) were diagnostic of malignancy and 7/30 (23.3%) remained non-diagnostic for malignancy. Of the 23 repeat FNAs diagnostic of malignancy: 16/23 (69.6%) were p16 positive and 7/23 (30.4%) were p16 indeterminate. In summary, 88/148 (59.5%) initial FNAs and 14/30 (46.7%) of repeat FNAs were non-diagnostic of malignancy or p16 indeterminate. Final yield of FNA biopsies (initial and first repeat FNA) to diagnose malignancy and p16 status was 70/148 (47.3%). CONCLUSIONS: Fine needle aspirations of lymph nodes in patients with HPV-associated OPSCC are frequently non-diagnostic for malignancy or indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.

Development of a Novel Molecular Test for Determining HPV Integration Status in HPV-Positive Oropharynx Cancers.

This diagnostic study describes the development of an assay for human papillomavirus­driven cancers of the oropharynx and the role viral integration could play in the process.

Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx.

Human papillomavirus-positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV subtype 16 (HPV16). Favorable treatment outcomes have led to increasing interest in treatment deescalation to reduce treatment-related morbidity. Prognostic biomarkers are needed to identify appropriately low-risk patients for reduced treatment intensity. Targeted DNA sequencing including all HPV16 open reading frames was performed on tumors from 104 patients with HPV16+ OPSCC treated at a single center. Genotypes closely related to the HPV16-A1 reference were associated with increased numbers of somatic copy-number variants in the human genome and poor recurrence-free survival (RFS). Genotypes divergent from HPV16-A1 were associated with favorable RFS. These findings were independent of tobacco smoke exposure. Total RNA sequencing was performed on a second independent cohort of 89 HPV16+ OPSCC cases. HPV16 genotypes divergent from HPV16-A1 were again validated in this independent cohort, to be prognostic of improved RFS in patients with moderate (less than 30 pack-years) or low (no more than 10 pack-years) of tobacco smoke exposure. In summary, we show in two independent cohorts that viral sequence divergence from the HPV16-A1 reference is correlated with improved RFS in patients with moderate or low tobacco smoke exposure. IMPLICATIONS: HPV16 genotype is a potential biomarker that could be easily adopted to guide therapeutic decision-making related to deescalation therapy.

Socioeconomic status, access to care, risk factor patterns, and stage at diagnosis for head and neck cancer among black and white patients.

BACKGROUND: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. METHODS: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance), and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. RESULTS: We identified three latent classes. Advanced T-stage was higher for black (RFD = +20.2%; 95% CI: -4.6 to 44.9) than white patients (RFD = +10.7%; 95% CI: 2.1-19.3) in the low-SES/high-access/high-behavioral risk class and higher for both black (RFD = +29.6%; 95% CI: 4.7-54.5) and white patients (RFD = +23.9%; 95% CI: 15.2-32.6) in the low-SES/low-access/high-behavioral risk class. CONCLUSION: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation.

Evaluation of a 3D-Printed Transoral Robotic Surgery Simulator Utilizing Artificial Tissue.

OBJECTIVES/HYPOTHESIS: Transoral robotic surgery (TORS) poses challenges for operators in training, with limited robot access on a platform requiring distinct surgical skills. Few simulators exist, and current virtual reality training modules exclude head and neck simulations. This study evaluates the construct validity for a novel low-cost TORS simulator. STUDY DESIGN: Single institution prospective observational study. METHODS: Using 3D-printed oral cavity structures and replaceable artificial tissue components, a modular TORS simulator was constructed for short-duration hands-on simulations with the da Vinci SI robot. Sixteen surgeons of differing robotic skill levels, no experience (novice), prior experience, and formal robot training, participated in simulated tonsil and tongue base tumor resections. Video recordings of each participant were graded by a blinded robotically trained surgeon using a 35-point Global Evaluative Assessment of Robotic Surgery (GEARS) criterion adapted for the TORS simulator. RESULTS: Operators reporting formal robotic training or prior robot experience achieved significantly higher mean total GEARS scores compared to novice operators (32 vs. 20.5; P < .001). Overall, mean total GEARS scores correlated with reported experience level; novice operators scored 54% of total points at 19 (4.5), operators with prior experience scored 82.3% of total points at 28.8 (2.6), and robotically trained operators scored 97.1% of total points at 34 (1.7). CONCLUSION: With a GEARS criterion, our simulator successfully differentiated novice from experienced and robotically trained operators of the da Vinci SI robot during simulated tonsillectomy and base of tongue resections. These findings support the construct validity of this prototype simulator and offer a foundation for further testing of predictive validity. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:1588-1593, 2022.

Quantifying smoking exposure, genomic correlates, and related risk of treatment failure in p16+ squamous cell carcinoma of the oropharynx.

OBJECTIVES: HPV-associated (p16+) squamous cell carcinoma of the oropharynx (OPSCC) has improved survival as compared to HPV-negative, smoking-associated disease. Intermediate outcomes have been noted in patients with p16+ tumors and smoking exposure. However, the extent of smoking exposure required for outcomes to decrease has not been delineated due to low failure rates and poor availability of quantitative tobacco smoke exposure data. Our primary objective is to characterize the dose-dependent relationship between recurrence-free survival (RFS) and tobacco smoke exposure in p16+ OPSCC and secondarily correlate tobacco smoke exposure with genomic alterations. METHODS: Single institution chart review was performed of patients diagnosed with p16+ OPSCC from 2003 to 2015. Patients were excluded if staging, treatment details, recurrence status, or smoking exposure in pack-years were not available. Two hundred and forty-four patients were included. RESULTS: Patients with 25 pack-years or greater smoking history exhibited a dose-dependent decrease in RFS compared to never smokers. This was robust to multivariate analysis for including staging and demographic factors. Forty-three patients with available targeted tumor sequencing data were identified. A strong trend was observed for increased C to A transversion mutations above 25 pack-years, which are known to be associated with exposure to tobacco smoke. Similarly, the proportion of COSMIC Signature 4 mutations were also found to be more common in patients with more than 25 pack-years of smoking exposure. CONCLUSION: Evidence-based smoking exposure thresholds are needed to define inclusion criteria for trials of de-escalation therapy for p16+ OPSCC. Patients with smoking exposure greater than 20 pack-years have increased risk of recurrence and a distinct pattern of genomic alterations. Further studies are needed to delineate the potential consequences of mild smoking exposure. Smoking-related mutational signatures may hold potential for biomarker development in p16+ OPSCC. LEVEL OF EVIDENCE: 2B.

Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma.

OBJECTIVE: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) MATERIALS AND METHODS: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). RESULTS: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5 years compared to patients with high SES (HR 3.11, 95% CI 2.07-4.67; p < 0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35-3.86; p < 0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92-4.56; p < 0.001). CONCLUSION: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC.

Open Approaches to Stensen Duct Scar.

Duct scar in the form of stenoses or stricture is the second leading cause of obstructive sialadenitis after stone. Over the past decade, there has been a growing experience demonstrating the effectiveness of endoscopic techniques in the minimally invasive management of salivary duct stenosis. Less information, however, is available with regard to open approaches for recurrent or complex ductal stenoses. This article reports on a case of gland preservation using an open ductal technique that originally was applied in cases of traumatic Stensen's duct injury.