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Background: Complications following head and neck microvascular free tissue transfer (MFTT) are common. Less is known about when they occur., Method: Retrospective study of patients with primary or recurrent head and neck cancer undergoing MFTT reconstruction at a tertiary care institution. MFTT reconstructions with inpatient postoperative complications were included. The Kruskal-Wallis test was used to compare median postoperative day (POD) onset of complication by flap type., Results: Of 1090 patients undergoing MFTT reconstruction, 126 (11.6%) patients experienced inpatient complications including fibula (n = 35), anterolateral thigh (n = 60), or radial forearm (n = 31) MFTTs. POD onset was shortest for surgical site hematoma (median = 1 [IQR 1-5]), and longest for donor site infection (median = 11.5 [IQR 8-15]). There was no significant difference between flap types and POD onset of complications (p > 0.05)., Conclusion: Hematoma formation and flap failure occur earliest during hospitalization, while dehiscence, infection, and fistula occur later. There is no difference in complication timing between flap types., (© 2024 Wiley Periodicals LLC.)

Background: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs., Methods: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing., Results: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies., Conclusion: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: New patient referrals are often processed by practice coordinators with little-to-no medical background. Treatment delays due to incorrect referral processing, however, have detrimental consequences. Identifying variables that are associated with a higher likelihood of surgical oncological resection may improve patient referral processing and expedite the time to treatment. The study objective is to develop a supervised machine learning (ML) platform that identifies relevant variables associated with head and neck surgical resection., Methods: A retrospective cohort study was conducted on 64 222 patient datapoints from the SEER database., Results: The random forest ML model correctly classified patients who were offered head and neck surgery with an 81% accuracy rate. The sensitivity and specificity rates were 86% and 71%. The positive and negative predictive values were 85% and 73%., Conclusions: ML modeling accurately predicts head and neck cancer surgery recommendations based on patient and cancer information from a large population-based dataset. ML adjuncts for referral processing may decrease the time to treatment for patients with cancer., (© 2024 Wiley Periodicals LLC.)

Background: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction., Methods: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed., Results: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013)., Conclusions: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients., (© 2023 Wiley Periodicals LLC.)

Background: Guidelines regarding head and neck surgical care have evolved during the coronavirus-19 (COVID-19) pandemic. Data on operative management have been limited., Methods: We compared two cohorts of patients undergoing head and neck or reconstructive surgery between March 16, 2019 and April 16, 2019 (pre-COVID-19) and March 16, 2020 and April 16, 2020 (COVID-19) at an academic center. Perioperative, intraoperative, and postoperative outcomes were recorded., Results: There were 63 operations during COVID-19 and 84 operations during pre-COVID-19. During COVID-19, a smaller proportion of patients had benign pathology (12% vs 20%, respectively) and underwent thyroid procedures (2% vs 23%) while a greater proportion of patients underwent microvascular reconstruction±ablation (24% vs 12%,). Operative times increased, especially among patients undergoing microvascular reconstruction±ablation (687 ± 112 vs 596 ± 91 minutes, P = .04). Complication rates and length of stay were similar., Conclusions: During COVID-19, perioperative outcomes were similar, operative time increased, and there were no recorded transmissions to staff or patients. Continued surgical management of head and neck cancer patients can be provided safely., (© 2020 Wiley Periodicals LLC.)

Background: Xerostomia is one of the most common long-term adverse effects of radiotherapy for head and neck cancer patients. Contralateral submandibular gland transfer (SMG-T) before radiotherapy was shown to reduce xerostomia compared to pilocarpine. We sought to evaluate a modification of this surgery preserving the ipsilateral facial artery and vein to simplify the SMG-T., Methods: Eighteen patients planned for head and neck intensity modulated radiotherapy to both necks were reviewed. Surgical complications were recorded. The grade of xerostomia was assessed after treatment completion., Results: There were no minor or major complications resulting from the modified SMG-T. At 24.5-months follow up, the incidence of post-treatment moderate to severe xerostomia was 16.7%. No locoregional recurrence occurred. Only one patient had distant solitary lung metastasis., Conclusion: The modified SMG-T technique is a practical and effective method to reduce the dose of radiation to the contralateral SMG and limit post-treatment xerostomia., (© 2020 Wiley Periodicals, Inc.)

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer (HPV-OPC) is distinct from HPV-unassociated head and neck cancer. However, whether risk factors for HPV-positive oropharyngeal and nonoropharyngeal squamous cell cancer are the same is unclear., Methods: Incident cases of HPV-positive head and neck cell cancer and matched non-cancer controls were enrolled in a multi-institutional, prospective study examining risk factors, biomarkers, and survival., Results: HPV-nonOPC (n = 20) were more likely to be ever smokers than controls (n = 80, OR 3.49, 95%CI 1.11-10.9) and HPV-OPC (n = 185, OR 3.28, 95%CI 1.10-10.2). Compared with HPV-OPC, HPV-nonOPC were less likely to have had over 3 oral sexual partners (OR 0.29, 95%CI 0.06-0.9), more likely to have multimorbidity (OR 3.30, 95%CI 1.04-10.5), and less likely to have antibodies to HPV16 E6 (90% vs 28%, OR 0.05, 95%CI 0.02-0.2). HPV-nonOPC had worse 4-year OS (77% vs 96%, P = .001) and RFS (69% vs 94%, P < .001) than HPV-OPC., Conclusions: HPV-positive nonoropharyngeal are distinct from HPV-positive oropharyngeal cancers., (© 2020 Wiley Periodicals, Inc.)

Background: This study examines the effect of insurance status (as a measure of socioeconomic status) on patient with benign thyroid disease., Methods: A retrospective review was performed among 60 patients undergoing total thyroidectomy for benign thyroid disease. Univariate and multivariable analyses examined the relationship between insurance status and thyroid volume (sum of the left and right lobe volumes)., Results: Twenty-eight (47%) patients were considered of underinsured/uninsured status, and 32 (53%) patients were considered of private/government/military insurance status. Median pathologic whole thyroid volume was 66 mL (range, 2-855). After multivariable linear regression, underinsured/uninsured status was the only significant predictor of larger volume (correlation coefficient [r] = 118; 95% CI, 42 to 194; P = .003), after adjusting for age, sex, body mass index, and presence of concomitant thyroid disease and compressive symptoms., Conclusion: Patients of underinsured/uninsured status suffered more severe disease presentations at time of thyroidectomy, as measured by larger thyroid volumes., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors., Methods: In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models., Results: The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage., Conclusion: In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system., (© 2018 Wiley Periodicals, Inc.)

Background: Despite its increasingly widespread adoption of transoral robotic surgery (TORS), there is still no uniform training curriculum. The purpose of this study was to describe the results of our novel TORS curriculum training program in which we introduce ex vivo dissection models for radical tonsillectomy and base of tongue (BOT) resections., Methods: Prospective blinded data collection and objective assessment of a novel training curriculum. Trainee performance was evaluated on objective structured assessments of technical skills (OSATS) metrics, measured resection time, and margin analysis. Additionally, 4 expert TORS surgeons completed the ex vivo dissections., Results: Trainees achieved OSATS scores similar to those of experts in both the BOT resection and radical tonsillectomy models. Peripheral and deep surgical margin measurements in the BOT model were significantly improved after training and were comparable to experts., Conclusion: This graduated curriculum provides a realistic training experience to develop competency with oropharyngeal resections before transition to the operating room. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1563, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Factors associated with disease-free survival (DFS) after salvage therapy for recurrent oropharyngeal squamous cell carcinoma (SCC) in the context of human papillomavirus (HPV) are poorly understood., Methods: A retrospective cohort analysis was conducted of patients with recurrent oropharyngeal SCC with known HPV tumor status who received salvage therapy., Results: Eighty-six patients were eligible for analysis. Sixty-four patients (74%) were HPV-positive. In multivariable analysis, HPV-positive tumor status (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.13-0.71; p = .007), clinical response to any salvage therapy (HR = 0.29; 95% CI = 0.11-0.77; p = .01), and surgical salvage (HR = 0.38; 95% CI = 0.16-0.88; p = .02) were associated with improved overall survival (OS). Positive surgical margin was associated with worse DFS after salvage (HR = 8.43; 95% CI = 1.99-35.70; p = .004)., Conclusion: For recurrent oropharyngeal SCC, HPV-positive tumor status, surgical salvage, and clinical response to salvage therapy are independently associated with improved OS, but not DFS after salvage. Surgical margin is the only independent predictor of DFS. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1501-E1509, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Adenoid cystic carcinoma (ACC) is an unusual salivary gland malignancy that remains poorly understood. Standard treatment, including surgery with postoperative radiation therapy, has attained reasonable local control rates, but the propensity for distant metastases has limited any improvement in survival over time. Our understanding of the molecular mechanisms driving ACC is quite rudimentary, due to the infrequent nature of its occurrence., Methods: An extensive literature review was performed on salivary gland ACCs and basic science research findings., Results: This review highlights many findings that are emerging about the carcinogenesis of ACC including cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations, mitochondrial alterations, and biomarker studies., Conclusion: Although there have been many discoveries, much still remains unknown about this rare malignancy. © 2011 Wiley Periodicals, Inc. Head Neck, 2011., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: The purpose of this study was to elucidate factors associated with pharyngoesophageal strictures after treatment for head and neck squamous cell carcinoma (SCC)., Methods: We conducted a retrospective review of patients receiving cisplatin and 5-fluorouracil chemotherapy combined with concurrent hyperfractionated radiation therapy for oropharyngeal squamous cell carcinoma., Results: Strictures developed in 13 of 67 patients (19%). Strictures were associated with tumor location (tonsil vs base of tongue; p = .03), neck dissection after completion of therapy (p = .03), and the duration of treatment-induced mucositis (weeks with mucositis grade ≥2; National Cancer Institute (NCI) Common Toxicity Criteria; p < .001). Age, sex, race, tumor stage, nodal stage, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, smoking, radiation dose, maximum severity of mucositis, amifostine use, and pretreatment swallow dysfunction were not significantly associated with stricture. In multivariate analysis, only duration of mucositis, after controlling for age, sex, and tumor location, remained highly significant (p < .01)., Conclusion: The duration of treatment-related mucositis is an independent risk factor for stricture formation in patients with oropharyngeal SCC treated with concurrent chemotherapy and radiation therapy., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: DNA repair genes play a critical role in maintaining genome stability and have been implicated in tumorigenesis. Head and neck squamous cell carcinoma (HNSCC) often shows chromosomal instability. We examined the expression of human RAD17, a DNA damage cell cycle checkpoint gene, in primary head and neck cancer tissue., Methods: Significance analysis of microarrays was applied to expression array results examining more than 12,000 genes in 7 samples of primary HNSCC and 6 samples of normal control oral epithelial tissue. Additional confirmation was performed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in these samples and western blot with an additional 12 primary HNSCC and 7 normal samples, followed by loss of heterozygosity (LOH) analysis and quantitative PCR at the RAD17 locus., Results: Multiple checkpoint and DNA repair genes were downregulated in primary head and neck tumor tissue compared with normal control epithelial tissue, including hRAD17. Its Z-score and fold change were -2.5 and 0.39, respectively. The results of normalized, quantitative RT-PCR showed decreased expression of hRAD17 mRNA in tumor tissue (mean value 0.2166) when compared with normal tissue (mean value 0.3957, p < .05). Western blot demonstrated undetectable expression of hRAD17 protein in primary tumor tissue (0/12), while there was strong expression of hRAD17 protein in normal oral mucosal tissue (6/7). To determine possible mechanisms of inactivation, the hRAD17 locus at 5q13 was analyzed using microsatellite markers, showing 70% LOH in 30 primary HNSCCs. Quantitative PCR showed that RAD17 DNA copy number was decreased in the majority of head and neck tumor tissue samples., Conclusion: Loss of hRAD17 expression occurs frequently in HNSCC, is often due to genomic deletion, and may facilitate genomic instability in HNSCC.

Background: A subset of patients with oral cavity squamous cell carcinoma(SCC), often of young age yet lacking a history of carcinogen exposure, has been identified, with no clear etiology for tumor development., Methods: To identify somatic genetic alterations unique to this patient population, we performed a high throughput single nucleotide polymorphism (SNP) analysis, quantitative PCR of the E6 and E7 regions of human papillomavirus (HPV) 16, sequencing of the IVSF-4+ locus of the FANC-C gene, and microsatellite analysis for 18 nonsmoking patients, age 23 to 57 years (median age, 39 years). We compared these results with oral SCC from 17 patients 47 to 81 (median, 64) years of age with significant tobacco exposure (>40 pack-years) to identify unique genetic alterations for each group., Results: SNP analysis demonstrated variable rates of allelic imbalance (AI) and no significant difference in terms of AI patterns between the two groups. However, we found an elevated rate of AI in chromosomal arms 6q (47% [17 of 36]) by performing microsatellite analysis of both groups. Only one tumor demonstrated the presence of HPV 16, and none of the tumors demonstrated mutations in the IVSF-4+ region of FANC-C., Conclusions: Despite variable marker density, SNP array analysis is an emerging technique for genome-wide assessment and is a useful tool for discovery of novel sites of allelic loss in oral SCC, including a novel region of allelic loss on chromosome 6q., (Copyright 2004 Wiley Periodicals, Inc.)