Faculty Bibliography

BACKGROUND:Transoral robotic surgery (TORS) was approved by the Food and Drug Administration in 2009 for the treatment of oropharyngeal cancers (oropharyngeal squamous cell carcinoma [OPSCC]). This study investigated the adoption and safety of TORS. METHODS:All patients who underwent TORS for OPSCC in the National Cancer Data Base from 2010 to 2016 were selected. Trends in the positive margin rate (PMR), 30-day unplanned readmission, and early postoperative mortality were evaluated. Outcomes after TORS, nonrobotic surgery (NRS), and nonsurgical treatment were compared with matched-pair survival analyses. RESULTS:From 2010 to 2016, among 73,661 patients with OPSCC, 50,643 were treated nonsurgically, 18,024 were treated with NRS, and 4994 were treated with TORS. TORS utilization increased every year from 2010 (n = 363; 4.2%) to 2016 (n = 994; 8.3%). The TORS PMR for base of tongue malignancies decreased significantly over the study period (21.6% in 2010-2011 vs 15.8% in 2015-2016; P = .03). The TORS PMR at high-volume centers (≥10 cases per year; 11.2%) was almost half that of low-volume centers (<10 cases per year; 19.3%; P < .001). The rates of 30-day unplanned readmission (4.1%) and 30-day postoperative mortality (1.0%) after TORS were low and did not vary over time. High-volume TORS centers had significantly lower rates of 30-day postoperative mortality than low-volume centers (0.5% vs 1.5%; P = .006). In matched-pair analyses controlling for clinicopathologic cofactors, 30-, 60-, and 90-day posttreatment mortality did not vary among patients with OPSCC treated with TORS, NRS, or nonsurgical treatment. CONCLUSIONS:TORS has become widely adopted and remains safe across the country with a very low risk of severe complications comparable to the risk with NRS. Although safety is excellent nationally, high-volume TORS centers have superior outcomes with lower rates of positive margins and early postoperative mortality.

The neck dissection is an integral component of comprehensive oncologic care for patients with head and neck cancer. Modern robotic surgical platforms are being utilized within otolaryngology for a growing number of indications, including, robot-assisted neck dissections. The proposed benefits of robot-assisted include improved cosmesis and reductions in post-operative lymphedema. Early data suggests that oncologic control following robot-assisted neck dissection is comparable to the gold-standard, open technique. Here we present review of the surgical techniques involved in a robot-assisted neck dissection as well as a review of perioperative care.

OBJECTIVES/HYPOTHESIS:The incidence of human papillomavirus-positive (HPV+) oropharyngeal cancer is rising, but public knowledge about this diagnosis remains low. This study aimed to investigate the quality and readability of online information about HPV+ oropharyngeal cancer. STUDY DESIGN:Cross-sectional website analysis. METHODS:This study conducted a total of 12 web searches across Google, Yahoo, and Bing to identify websites related to HPV+ oropharyngeal cancer. The QUality Evaluation Scoring Tool (QUEST) was used to measure quality based on seven website criteria. The Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL) were used to measure readability, with scores estimating the education level a reader would require to understand a piece of text. Readability improves as FRES increases and FKGL decreases. RESULTS:Twenty-seven unique web pages were evaluated. The mean USA reading grade level as measured by FKGL was 10.42 (standard deviation = 1.54). There was an inverse relationship between quality and readability, with a significant positive correlation between QUEST score and FKGL (r = 0.343, P = .040) and a significant negative correlation between QUEST score and FRES (r = -0.537, P = .002). CONCLUSIONS:With a mean USA reading grade level more than four grades above the American Medical Association's recommendation and results indicating that readability suffers as quality improves, these findings suggest that the currently available online information about HPV+ oropharyngeal cancer is insufficient. Improved patient education practices and resources about this diagnosis are needed. LEVEL OF EVIDENCE:NA Laryngoscope, 131:87-94, 2021.

Despite the success of immune checkpoint blockade therapy, few strategies sufficiently overcome immunosuppression within the tumor microenvironment (TME). Targeting regulatory T cells (T_regs) is challenging, because perturbing intratumoral T_reg function must be specific enough to avoid systemic inflammatory side effects. Thus, no T_reg-targeted agents have proven both safe and efficacious in patients with cancer. Neuropilin-1 (NRP1) is recognized for its role in supporting intratumoral T_reg function while being dispensable for peripheral homeostasis. Nonetheless, little is known about the biology of human NRP1⁺ T_regs and the signals that regulate NRP1 expression. Here, we report that NRP1 is preferentially expressed on intratumoral T_regs across six distinct cancer types compared to healthy donor peripheral blood [peripheral blood lymphocyte (PBL)] and site-matched, noncancer tissue. Furthermore, NRP1⁺ T_reg prevalence is associated with reduced progression-free survival in head and neck cancer. Human NRP1⁺ T_regs have broad activation programs and elevated suppressive function. Unlike mouse T_regs, we demonstrate that NRP1 identifies a transient activation state of human T_regs driven by continuous T cell receptor (TCR) signaling through the mitogen-activated protein kinase pathway and interleukin-2 exposure. The prevalence of NRP1⁺ T_regs in patient PBL correlates with the intratumoral abundance of NRP1⁺ T_regs and may indicate higher disease burden. These findings support further clinical evaluation of NRP1 as a suitable therapeutic target to enhance antitumor immunity by inhibiting T_reg function in the TME.

BACKGROUND:Transcervical arterial ligation has been studied as a useful procedure to prevent bleeding events after transoral robotic surgery (TORS). METHODS:A systematic review of English-language literature on arterial ligation in TORS from 2005 to 2019 was conducted using Cochrane, PubMed, Web of Science (WoS), and ScienceDirect databases. Studies evaluating ligation and rates of postoperative hemorrhage were included. Meta-analysis of included studies was performed to assess impact of ligation on postoperative hemorrhage. RESULTS:Five studies with 2008 patients were included. History of radiation (odds ratio [OR] = 2.26, P = .02) and advanced tumor stage (OR = 1.93, P = .02) were found to predispose patients to postoperative hemorrhage. Arterial ligation was protective against severe hemorrhage in the mixed primary surgical modality cohort (OR = 0.33, P = .03) and in the TORS-only subgroup (OR = 0.21, P = .02), but did not significantly impact overall odds of postoperative hemorrhage. CONCLUSION:Transcervical arterial ligation offers protection against major/severe postoperative hemorrhage in patients undergoing TORS. LEVEL OF EVIDENCE:II.

OBJECTIVES:To determine which surgical factors are associated with quality-of-life (QOL) outcomes in oral cavity cancer survivors after free flap reconstruction of the oral cavity. PATIENTS AND METHODS:A cross-sectional study was conducted from a multidisciplinary head and neck cancer (HNC) survivorship clinic. Oral cavity cancer survivors with at least 6-months of postoperative follow-up from ablation and free flap reconstruction were included. Primary outcome measures were validated patient-reported outcome measures (PROMs) including the Eating Assessment Tool-10 (EAT-10) measure of swallowing-specific QOL, University of Washington Quality of Life (UW-QOL) physical and social-emotional subscale scores and feeding tube dependence. RESULTS:Extent of tongue resection was associated with EAT-10 and the UW-QOL Physical subscale scores. Patients with oral tongue defects reported worse scores than with composite defects in the EAT-10 and UW-QOL physical domain (p = 0.0004, 0.0025, respectively). This association no longer applies when controlling for differences in extent of tongue resection. Patients with anterior composite resections reported worse EAT-10 scores than lateral resections (p = 0.024). This association no longer applies when controlling for extent of tongue resection (p = 0.46). Gastric tube dependence demonstrates similar trends to PROMs. CONCLUSION:Extent of tongue resection was strongly associated with poor QOL outcomes after free tissue reconstruction of the oral cavity and mediates the associations between other defect characteristics and QOL. These findings demonstrate the need for emphasis on expected oral tongue defects when counseling patients and highlight the need to address QOL in a multidisciplinary fashion post-operatively.

Current immunotherapy paradigms aim to reinvigorate CD8⁺ T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV⁺), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV⁺ HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV⁺ HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.

OBJECTIVE:To analyze the role of transoral robotic base-of-tongue mucosectomy in a cohort of patients with human papilloma virus negative unknown primary carcinoma. STUDY DESIGN:Retrospective database analysis. METHODS:A retrospective database review from 2012 to 2018 was performed at two large tertiary centers to study patients with human papilloma virus (HPV)-negative unknown primary carcinoma who underwent transoral robotic base-of-tongue mucosectomy. P16 testing was used as a surrogate for HPV status. Patients were included that had squamous cell carcinoma metastatic to the lateral neck based on fine needle aspiration or open biopsy. Preoperatively, all patients were classified as having an unknown primary based on normal clinical and flexible endoscopic exam, normal operative endoscopy, nonlocalizing imaging, and tonsillectomy. All patients underwent robotic base-of-tongue mucosectomy. The primary outcome measure was the incidence of pathologic identification of a mucosal primary. RESULTS:Twenty-three patients with p16-negative unknown primary carcinoma were identified and studied. All patients underwent transoral robotic base-of-tongue mucosectomy. Median age was 60 years at the time of diagnosis, and 18 of 23 (78.2%) were male. Pathologic analysis of the base-of-tongue specimens showed a primary tumor in only three of 23 (13.0%) of patients. CONCLUSION:Despite prior evidence suggesting a high rate of primary site identification in HPV-related disease, robotic base-of-tongue mucosectomy may not be indicated for HPV-negative unknown primary carcinoma based on a low likelihood of finding the primary. LEVEL OF EVIDENCE:4 Laryngoscope, 131:78-81, 2021.

BACKGROUND:Insufficient exposure may require termination of procedure in transoral robotic surgery (TORS). The aim of study was to develop a "Pharyngoscore" to quantify the risk of difficult oropharyngeal exposure (DOE) before TORS. METHODS:Three-hundred six patients undergoing any surgical procedure at one Academic Hospital were prospectively enrolled. Oropharynx was exposed with Feyh-Kastenbauer retractor. Exposure was evaluated by direct and endoscopic visualization of the four oropharyngeal subsites. Preoperative clinical/anthropometric parameters were studied in good oropharyngeal exposure and DOE groups. Logistic regression was performed to explore association between clinical/anthropometric parameters and DOE. Statistically significant parameters at multivariate analysis were incorporated into a nomogram. RESULTS:Sixty-five (21.2%) subjects were characterized by DOE. Variables associated with DOE at univariate analysis were male (p = 0.031), modified Mallampati Class (MMC) ≥ III (p < 0.001), smaller interincisor gap (p < 0.001), and larger neck circumference (p = 0.006). MMC, interincisor gap, and neck circumference were significant at multivariate analysis and were presented with a nomogram for creating the Pharyngoscore. CONCLUSIONS:The Pharyngoscore is a promising tool for calculating DOE probability before TORS.