Electrocochleography-Based Tonotopic Map: I. Place Coding of the Human Cochlea With Hearing Loss.

OBJECTIVES: Due to the challenges of direct in vivo measurements in humans, previous studies of cochlear tonotopy primarily utilized human cadavers and animal models. This study uses cochlear implant electrodes as a tool for intracochlear recordings of acoustically evoked responses to achieve two primary goals: (1) to map the in vivo tonotopy of the human cochlea, and (2) to assess the impact of sound intensity and the creation of an artificial "third window" on this tonotopic map. DESIGN: Fifty patients with hearing loss received cochlear implant electrode arrays. Postimplantation, pure-tone acoustic stimuli (0.25 to 4 kHz) were delivered, and electrophysiological responses were recorded from all 22 electrode contacts. The analysis included fast Fourier transformation to determine the amplitude of the first harmonic, indicative of predominantly outer hair cell activity, and tuning curves to identify the best frequency (BF) electrode. These measures, coupled with postoperative imaging for precise electrode localization, facilitated the construction of an in vivo frequency-position function. The study included a specific examination of 2 patients with auditory neuropathy spectrum disorder (ANSD), with preserved cochlear function as assessed by present distortion-product otoacoustic emissions, to determine the impact of sound intensity on the frequency-position map. In addition, the electrophysiological map was recorded in a patient undergoing a translabyrinthine craniotomy for vestibular schwannoma removal, before and after creating an artificial third window, to explore whether an experimental artifact conducted in cadaveric experiments, as was performed in von Békésy landmark experiments, would produce a shift in the frequency-position map. RESULTS: A significant deviation from the Greenwood model was observed in the electrophysiological frequency-position function, particularly at high-intensity stimulations. In subjects with hearing loss, frequency tuning, and BF location remained consistent across sound intensities. In contrast, ANSD patients exhibited Greenwood-like place coding at low intensities (~40 dB SPL) and a basal shift in BF location at higher intensities (~70 dB SPL or greater). Notably, creating an artificial "third-window" did not alter the frequency-position map. CONCLUSIONS: This study successfully maps in vivo tonotopy of human cochleae with hearing loss, demonstrating a near-octave shift from traditional frequency-position maps. In patients with ANSD, representing more typical cochlear function, intermediate intensity levels (~70 to 80 dB SPL) produced results similar to high-intensity stimulation. These findings highlight the influence of stimulus intensity on the cochlear operational point in subjects with hearing loss. This knowledge could enhance cochlear implant programming and improve auditory rehabilitation by more accurately aligning electrode stimulation with natural cochlear responses.

Multidimensional profiling of human T cells reveals high CD38 expression, marking recent thymic emigrants and age-related naive T cell remodeling.

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38hi expression universally identified CD8+ and CD4+ RTEs. We further determined the dynamics of RTEs and mature cells in a cohort of 158 individuals, including age-associated transcriptional reprogramming and shifts in cytokine production. Spectral cytometry profiling revealed two axes of aging common to naive CD8+ and CD4+ T cells: (1) a decrease in CD38++ cells (RTEs) and (2) an increase in CXCR3hi cells. Identification of RTEs enables direct assessment of thymic health. Furthermore, resolving the dynamics of naive T cell remodeling yields insight into vaccination and infection responsiveness throughout aging.

Chimeric Versus Multiple Simultaneous Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: To describe our experience with chimeric flaps and to assess the surgical outcomes and postoperative complications associated with chimeric flaps compared to multiple flaps. STUDY DESIGN/METHODS: Patients undergoing chimeric and multiple simultaneous free tissue transfer between June 2016 and October 2023 were retrospectively reviewed. The primary outcome of interest was the complication rate. Major complications required takeback to the operating room, hospital readmission, or transfer to the intensive care unit. Minor complications were managed conservatively. Secondary outcomes included operative time, length of hospitalization, and flap survival. SETTING: Academic tertiary care center. RESULTS: Our analysis included 113 patients (chimeric n = 38, multiple n = 75). We found no significant difference in operative times or minor complications. Chimeric flaps were associated with a shorter length of hospitalization. The major complication rate was higher for chimeric flaps (42.1% vs 22.7%, P = .03), but each cohort only had 1 instance of total flap loss. CONCLUSION: The complexity of large head and neck defects poses a reconstructive challenge for microvascular surgeons. Our findings suggest that chimeric and multiple flaps both produce acceptable complication rates when used appropriately. Differences in complication rates may reflect differences in utilization. The chimeric flap remains a valuable option for those with prior radiation or radical resection, but it remains unclear the degree to which they lessen the inherent risk of postoperative complications within this population. Each technique must be weighed in context of the patient's reconstructive profile and the institution's surgical capabilities to optimize long-term outcomes.

Clinical applications of vascularized fascia lata in head and neck reconstruction: A systematic review.

BACKGROUND: Given limitations in the current literature, the precise indications, techniques, and outcomes relevant to vascularized fascia lata free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature to evaluate indications, methods, and complications for vascularized fascia lata free flap reconstruction. METHODS: A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the head and neck region using vascularized fascia lata. Articles were reviewed based on relevance, with the primary outcome being surgical complications and surgical indications. RESULTS: A comprehensive search revealed 783 articles and 5 articles were ultimately found to be appropriate to this review- 55 patients undergoing free flap reconstruction were identified. Overall complication rates were 10.9 % for major complications and 18.1 % for minor complications. Follow-up spanned 1 to 95 months with a median of 48 months. CONCLUSIONS: Microvascular reconstruction of the head and neck with vascularized fascia lata is achievable with high adaptability and reliability reported in the literature.

Factors Associated with Head and Neck Cancer Postoperative Radiotherapy Delays: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is included in the National Comprehensive Cancer Network Clincal Practice Guidelines and is a Commission on Cancer quality metric. Factors associated with delays in starting PORT have not been systematically described nor synthesized. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: We included studies describing demographic characteristics, clinical factors, or social determinants of health associated with PORT delay (>6 weeks) in patients with HNSCC treated in the United States after 2003. Meta-analysis of odds ratios (ORs) was performed on nonoverlapping datasets. RESULTS: Of 716 unique abstracts reviewed, 21 studies were included in the systematic review and 15 in the meta-analysis. Study sample size ranged from 19 to 60,776 patients. In the meta-analysis, factors associated with PORT delay included black race (OR, 1.46, 95% confidence interval [CI]: 1.28-1.67), Hispanic ethnicity (OR, 1.37, 95% CI, 1.17-1.60), Medicaid or no health insurance (OR, 2.01, 95% CI, 1.90-2.13), lower income (OR, 1.38, 95% CI, 1.20-1.59), postoperative admission >7 days (OR, 2.92, 95% CI, 2.31-3.67), and 30-day hospital readmission (OR, 1.37, 95% CI, 1.29-1.47). CONCLUSION: Patients at greatest risk for a delay in initiating guideline-adherent PORT include those who are from minoritized communities, of lower socioeconomic status, and experience postoperative challenges. These findings provide the foundational evidence needed to deliver targeted interventions to enhance equity and quality in HNSCC care delivery.

A hybrid epithelial/mesenchymal state in head and neck cancer: A biomarker for survival with differential prognosis by self-reported race.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts. METHODS: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans. FINDINGS: The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported race and ethnicity, with a stronger association in non-Hispanic Black patients. Black patients with a high hybrid E/M score had a higher risk of death or recurrence (hazard ratio [HR]: 4.18 [95% confidence interval (CI): 2.06, 8.49]) than White patients with a high hybrid E/M score (HR: 1.58 [95% CI: 1.11, 2.26]). CONCLUSION: Our results suggest a complex interplay of social structure, racism, and genetic diversity. We implore researchers to consider the social and biological context contributing to disparities. FUNDING: A.L.M. received support from the National Institute of Minority Health and Health Disparities (K01MD013897 [principal investigator (PI), A.L.M.]). S.V.P. received support from the National Institute of Dental and Craniofacial Research (R01DE032865 [PI, S.V.P.] and R01DE032371 [PI, S.V.P.]).

Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer.

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. Design, Setting, and Participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. Main Outcome Measures and Measures: The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Results: Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Conclusions and Relevance: Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.

Blocking senescence and tolerogenic function of dendritic cells induced by γδ Treg cells enhances tumor-specific immunity for cancer immunotherapy.

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy. METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence and dysfunction induced by Treg cells. Impaired tumor antigen HER2-specific recognition and immune response of senescent DCs induced by γδ Treg cells were explored in vitro and in vivo in humanized mouse models. In addition, the DC-based HER2 tumor vaccine immunotherapy in breast cancer models was performed to explore the enhanced antitumor immunity via prevention of DC senescence through blockages of STAT3 and programmed death-ligand 1 (PD-L1) signaling. RESULTS: We showed that tumor-derived γδ Treg cells promote the development of senescence in DCs with tolerogenic functions in breast cancer. Senescent DCs induced by γδ Treg cells suppress Th1 and Th17 cell differentiation but promote the development of Treg cells. In addition, we demonstrated that PD-L1 and STAT3 signaling pathways are critical and involved in senescence induction in DCs mediated by tumor-derived γδ Treg cells. Importantly, our complementary in vivo studies further demonstrated that blockages of PD-L1 and/or STAT3 signaling can prevent γδ Treg-induced senescence and reverse tolerogenic functions in DCs, resulting in enhanced HER2 tumor-specific immune responses and immunotherapy efficacy in human breast cancer models. CONCLUSIONS: These studies not only dissect the suppressive mechanism mediated by tumor-derived γδ Treg cells on DCs in the tumor microenvironment but also provide novel strategies to prevent senescence and dysfunction in DCs and enhance antitumor efficacy mediated by tumor-specific T cells for cancer immunotherapy.

Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection.

OBJECTIVES: To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND). METHODS: A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded. RESULTS: Of 126 patients (46 [37%] staged and 80 [63%] concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 [95% CI 0.9-1.8] hours), length of stay (1.0 [1.0-1.0] day), and time between primary surgery and adjuvant therapy initiation (4.0 [0.0-8.0] days) were lower in the concurrent BND cohort. CONCLUSION: Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

Poor Dental Health as a Risk Factor for Alveolar Ridge Malignancies.

OBJECTIVE: To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. STUDY DESIGN: Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. RESULTS: Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). CONCLUSIONS: This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted.

Delays Starting Postoperative Radiotherapy Among Head and Neck Cancer Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT. DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL. REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures was performed on nonoverlapping datasets to examine the pooled frequency of PORT delays and time-to-PORT. RESULTS: Thirty-six studies were included in the systematic review and 14 in the meta-analysis. Most studies utilized single-institution (n = 17; 47.2%) or cancer registry (n = 16; 44.4%) data. Twenty-five studies (69.4%) defined PORT delay as >6 weeks after surgery (the definition utilized by the CoC and National Comprehensive Cancer Network Guidelines), whereas 4 (11.1%) defined PORT delay as a time interval other than >6 weeks, and 7 (19.4%) characterized time-to-PORT without defining delay. Meta-analysis revealed that 48.6% (95% confidence interval [CI], 41.4-55.9) of patients started PORT > 6 weeks after surgery. Median and mean time-to-PORT were 45.8 (95% CI, 42.4-51.4 days) and 47.4 days (95% CI, 43.4-51.4 days), respectively. CONCLUSION: Delays in initiating guideline-adherent PORT occur in approximately half of patients with HNSCC. These meta-analytic data can be used to set national benchmarks and assess progress in reducing delays.

Patient Navigation for Timely, Guideline-Adherent Adjuvant Therapy for Head and Neck Cancer: A National Landscape Analysis.

BACKGROUND: Aligned with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers, in November 2021 the Commission on Cancer approved initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery for head and neck cancer (HNC) as its first and only HNC quality metric. Unfortunately, >50% of patients do not commence PORT within 6 weeks, and delays disproportionately burden racial and ethnic minority groups. Although patient navigation (PN) is a potential strategy to improve the delivery of timely, equitable, guideline-adherent PORT, the national landscape of PN for this aspect of care is unknown. MATERIALS AND METHODS: From September through November 2022, we conducted a survey of health care organizations that participate in the American Cancer Society National Navigation Roundtable to understand the scope of PN for delivering timely, guideline-adherent PORT for patients with HNC. RESULTS: Of the 94 institutions that completed the survey, 89.4% (n=84) reported that at least part of their practice was dedicated to navigating patients with HNC. Sixty-eight percent of the institutions who reported navigating patients with HNC along the continuum (56/83) reported helping them begin PORT. One-third of HNC navigators (32.5%; 27/83) reported tracking the metric for time-to-PORT at their facility. When estimating the timeframe in which the NCCN and Commission on Cancer guidelines recommend commencing PORT, 44.0% (37/84) of HNC navigators correctly stated ≤6 weeks; 71.4% (60/84) reported that they did not know the frequency of delays starting PORT among patients with HNC nationally, and 63.1% (53/84) did not know the frequency of delays at their institution. CONCLUSIONS: In this national landscape survey, we identified that PN is already widely used in clinical practice to help patients with HNC start timely, guideline-adherent PORT. To enhance and scale PN within this area and improve the quality and equity of HNC care delivery, organizations could focus on providing better education and support for their navigators as well as specialization in HNC.

Epigenetic regulation during cancer transitions across 11 tumour types.

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.

Free Flap Outcomes for Head and Neck Surgery in Patients with COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) affects the vascular system, subjecting patients to a hypercoagulable state. This is of particular concern for the success of microvascular free flap reconstruction. This study aims to report head and neck free flap complications in patients with COVID-19 during the perioperative period. We believe these patients are more likely to experience flap complications given the hypercoagulable state. METHODS: This is a multi-institutional retrospective case series of patients infected with COVID-19 during the perioperative period for head and neck free flap reconstruction from March 2020 to January 2022. RESULTS: Data was collected on 40 patients from 14 institutions. Twenty-one patients (52.5%) had a positive COVID-19 test within 10 days before surgery and 7 days after surgery. The remaining patients had a positive test earlier than 10 days before surgery. A positive test caused a delay in surgery for 16 patients (40.0%) with an average delay of 44.7 days (9-198 days). Two free flap complications (5.0%) occurred with no free flap deaths. Four patients (10.0%) had surgical complications and 10 patients had medical complications (25.0%). Five patients (12.5%) suffered from postoperative COVID-19 pneumonia. Three deaths were COVID-19-related and one from cancer recurrence during the study period. CONCLUSION: Despite the heightened risk of coagulopathy in COVID-19 patients, head and neck free flap reconstructions in patients with COVID-19 are not at higher risk for free flap complications. However, these patients are at increased risk of medical complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

Neighborhood socioeconomic status and race are associated with incidence disparities in oral cavity cancers.

OBJECTIVES: To determine the association between neighborhood socioeconomic status (nSES), race and incidence rate trends of oral cavity cancer (OCC). MATERIALS AND METHODS: We used data from the SEER (Surveillance, Epidemiology, and End Results) 18 Census Tract-level SES and Rurality Database (2006-2018) database of the National Cancer Institute to create cohorts of OCC patients between 2006 and 2018. Annual incidence rates were calculated and trends in rates were estimated using joinpoints regression. RESULTS: The incidence of OCC is the highest among low nSES White Americans (2.86 per 100 000 persons) and the lowest among high nSES Black Americans (1.17 per 100 000 persons). Incidence has significantly increased among Asian Americans (annual percent change [APC]: low nSES-2.4, high nSES-2.6) and White Americans (APC: low nSES-1.4, high nSES-1.6). Significant increases in the incidence of oral tongue cancer in these groups primarily drive this increase. Other increases were noted in alveolar ridge cancer among White Americans and hard palate cancer among Asian Americans. OCC incidence decreased significantly in Hispanic Americans of high nSES (APC: -2.5) and Black Americans of low nSES (APC: -2.7). Floor of mouth cancer incidence decreased among most groups. CONCLUSION: Despite the overall decreasing incidence of OCC, these trends are inconsistent among all OCC subsites. Differences are seen by race, nSES, and subsite, indicating intersectional barriers that extend beyond nSES and race and ethnicity alone. Further research on risk factors and developing interventions targeting vulnerable groups is needed.

Functional considerations between flap and non-flap reconstruction in oral tongue cancer: A systematic review.

This systematic review aims to provide insight into the ideal reconstructive approach of the oral tongue in oral tongue cancer (OTC) by investigating the relationship between functional outcomes and the extent of tongue resection. A structured search was performed in Ovid MEDLINE, EMBASE, and Web of Science. Studies comparing patient-reported and objective measurements of the oral tongue function between flap vs. non-flap reconstruction were included. Functional outcomes of interest were speech production, deglutition efficiency, tongue mobility, overall quality of life, and postoperative complications. A total of nine studies were retrieved and critically appraised. Patients with 20 % or less of oral tongue resected had superior swallowing efficiency and speech intelligibility with a non-flap reconstruction while patients with a tongue defect of 40-50 % self-reported or demonstrated better swallowing function with a flap repair. The data in intermediate tongue defects (20-40 % tongue resected) was inconclusive, with several studies reporting comparable functional outcomes between approaches. A longitudinal multi-institutional prospective study that rigidly controls the extent of tongue resected and subsites involved is needed to determine the percentage of tongue resected at which a flap reconstruction yields a superior functional result in OTC.