Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Influence of Otolaryngological Subspecialties on Perception of Transoral Robotic Surgery: An International YO-IFOS Survey.

BACKGROUND: To investigate perception, adoption, and awareness on the part of otolaryngology and head and neck surgeons (OTO-HNS) of transoral robotic surgery (TORS). METHODS: Several items assessed: awareness/perception; access to TORS; training; indications and advantages/hurdles to TORS practice. A subanalysis was performed to assess differences according to the identified otolaryngological subspecialties. RESULTS: A total of 359 people completed the survey. Among subspecialties, while for otolaryngologists 30/359 (8.4%) and H&N surgeons 100/359 (27.9%) TORS plays an effective role in hospital stay, laryngologists frequently disagreed (54.3%). There was a lower incidence among rhinologists and otologists (1.9%). Pediatric surgeons (0.8%) reported a positive response regarding the adoption of robotic surgery, and head and neck specialists expressed an even greater response (14.2%). Low adherence was related to perceived cost-prohibitive TORS, by 50% of H&N surgeons. CONCLUSIONS: Perception, adoption, and knowledge about TORS play a key role in the application of the robotic system, significantly varying across subspecialties.

Laryngeal cancer treatment decision making: A conjoint analysis of general public attitudes and priorities.

Objective: Patients with advanced laryngeal cancer are typically presented with divergent treatment options, namely chemoradiation versus total laryngectomy. This study aims to understand general perspectives of the factors involved in this decision-making process. Methods: Surveys were constructed using specialized conjoint analysis software. Seven attributes integral to the decision-making process for advanced laryngeal cancer treatment were included. Results: Three hundred one healthy adult volunteers completed the decision-making program. The relative impact of each treatment attribute on decision making across all participants was scored with an average importance score (standard deviation) as follows: Lifespan 22.2% (±8.5), Voicing 21.4% (±5.9), Swallowing 19.1% (±7.3), Cancer Cure 14.9% (±6.2), Mode of Breathing 11.0% (±3.7), Self-Image 6.7% (±2.9), and Treatment Type 4.8% (±3.0). Conclusions: General public opinion ranked lifespan, voicing, and swallowing aspects as similarly important, and all were ranked more important than probability of cure. These data demonstrate a variety of priorities among participants and the need for tailored discussions when determining treatment choice for advanced laryngeal cancer. Level of Evidence: Level 4.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Transoral Robotic Surgery for a Parapharyngeal Space Tumor.

A 71-year-old woman had a parapharyngeal space mass that was found on magnetic resonance imaging of the face. She experienced left jaw tightness, aural fullness, and facial discomfort. What is your diagnosis?

Morphometric Analysis and Observer Perceptions Following Transvestibular Chondrolaryngoplasty.

OBJECTIVES: To assess novel morphometric measurement strategies and observer perception ratings as potential metrics for evaluating gender-affirming transvestibular chondrolaryngoplasty in reducing contour protrusion of the neck. METHODS: High-resolution preoperative and 3-month postoperative photographs of a pilot series of 10 patients (n = 10) who underwent endoscopic transvestibular chondrolaryngoplasty were collected. Morphometric measurements of "light reflex" and lateral view thyroid protrusion angles of the neck contours were analyzed. Pre- and postoperative photographs were presented in random order in a survey to 17 untrained judges and rated on perceived masculinity/femininity and thyroid notch protrusion on a 7-point scale. A pre- to postoperative change in morphometric angles and subjective ratings was assessed using paired t-tests and Wilcoxon signed-rank tests. RESULTS: Mean light reflex angles were reduced after surgery from 78.6° to 40.5° in the anterior neutral view (P = .0003), from 45.2° to 24.4° in the anterior extended view (P = .003), and from 7.03° to 4.32° in the lateral view (P = .006). Median survey ratings of neck photographs were improved after surgery, from 4 to 3 in gender perception toward more feminine perception (P < .0001) and from 4 to 2 in thyroid protrusion toward less protrusive perception (P < .0001). CONCLUSIONS: Morphometric analysis in anterior and lateral views as well as subjective gender perception and contour protrusion measures following feminization chondrolaryngoplasty by endoscopic transvestibular scarless approach demonstrate encouraging possibilities as outcome evaluation measures for chondrolaryngoplasty.

Adoption of otolaryngologist-head neck surgeons toward transoral robotic surgery: An international survey.

Objective: To investigate perception, adoption and awareness of otolaryngologist-head neck surgeons (OTO-HNS) toward transoral robotic surgery (TORS). Methods: An online survey was sent to 1383 OTO-HNS on the perception, adoption and awareness about TORS to members of many otolaryngological societies. The following aspects were assessed: TORS access; training; awareness/perception; indications and advantages/barriers to TORS practice. The responses were presented for the entire cohort and regarding the TORS experience of OTO-HNS. Results: A total of 359 completed the survey (26%); including 115 TORS surgeons. TORS-surgeons carry out a mean number of 34.4 annual TORS procedures. The primary barriers to TORS were the cost of the robot (74%) and disposable accessories (69%), and the lack of training opportunity (38%). The 3D view of the surgical field (66%), the postoperative quality of life outcomes (63%) and the shorter hospital stay (56%) were the most important benefits of TORS. TORS-surgeons believed more frequently that TORS is indicated for cT1-T2 oropharyngeal and supraglottic cancers than non-TORS surgeons (p < .005). Participants believed that the priorities for the future consisted of the reduction of the robot arm size and the incorporation of flexible instruments (28%); the integration of laser (25%) or GPS tracking based on imaging (18%), all of them to improve accesses to hypopharynx (24%), supraglottic larynx (23%) and vocal folds (22%). Conclusions: The perception, adoption and knowledges toward TORS depend on the access to robot. The findings of this survey may help guide decisions on how improve the dissemination of TORS interest and awareness.

Evaluation and application of CO2 laser fiber delivery for single port transoral robotic surgery.

BACKGROUND: Transoral robotic surgery (TORS) using the Single-Port system (SPS) relies on electrocautery, limiting its applications in the upper aerodigestive tract. We evaluated the feasibility of a CO2 delivery system for the SPS. METHODS: Otolaryngology residents performed a cutting exercise using a handheld CO2 laser and participated in a cadaveric oropharyngeal dissection using the SPS with monopolar cautery (SP + EC) and CO2 laser (SP + CO2 ). Residents completed the System Usability Scale (SUS) questionnaire to evaluate these techniques. RESULTS: The same laser fiber was used for all combined dissections. The handheld CO2 laser, SP + EC, and SP + CO2 demonstrated similar SUS scores. On individual domain scores, SP + CO2 received less favorable ratings compared to the handheld CO2 laser for complexity, integration, and cumbersome experience (p < 0.05). On subgroup stratification, less TORS experience was associated with worse SUS scores. CONCLUSION: SP-guided CO2 laser delivery is a viable alternative to electrocautery in robotic surgery, and should be considered when performing TORS.

Effect of Gender-affirming Facial Feminization Surgery on Psychosocial Outcomes.

OBJECTIVE: This study investigates the effect of gender-affirming facial feminization surgery (FFS) on psychosocial outcomes in patients with gender dysphoria. BACKGROUND: Comprehensive analyses of psychosocial outcomes after gender-affirming FFS are absent in the literature resulting in a paucity of information on the impact of FFS on quality of life as well as ramifications in health insurance coverage of FFS. METHODS: Scores from 11 validated, quantitative instruments from the Patient-Reported Outcomes Measurement Information System (PROMIS) assessing anxiety, anger, depression, global mental health, global physical health, satisfaction with sex life, positive affect, emotional support, social isolation, companionship, and meaning and purpose. Patients within the preoperative group (pre-FFS) were evaluated >30 days before surgery and patients within the postoperative group (post-FFS) were evaluated ≥10 weeks after surgery. RESULTS: A total of 169 patients [mean (SD) age, 33.5 (10.8) years] were included. Compared with the pre-FFS group (n=107), the post-FFS group (n=62) reported improved scores anxiety (56.8±8.8 vs 60.1±7.9, P =0.01), anger (47.4±7.6 vs 51.2±9.6, P =0.01), depression (52.2±9.2 vs 57.0±8.9, P =0.001), positive affect (46.6±8.9 vs 42.9±8.7, P =0.01), meaning and purpose (49.9±10.7 vs 46.2±10.5, P =0.03), global mental health (46.7±7.6 vs 43.1±9.2, P =0.01), and social isolation (52.2±7.5 vs 55.4±7.4, P =0.01). Multivariable analysis to account for the effects of other gender-affirming surgeries, hormone therapy duration, preexisting mental health diagnoses, socioeconomic disparities, and patient-reported quality of social relationships on psychosocial functioning demonstrated that completion of FFS was independently predictive of improved scores. CONCLUSIONS: Gender-affirming FFS improves the quality of life by multiple psychosocial domains in transfeminine patients.

Correlating Perceptual Voice Quality in Adductor Spasmodic Dysphonia With Computer Vision Assessment of Glottal Geometry Dynamics.

PURPOSE: This study examined the relationship between voice quality and glottal geometry dynamics in patients with adductor spasmodic dysphonia (ADSD). METHOD: An objective computer vision and machine learning system was developed to extract glottal geometry dynamics from nasolaryngoscopic video recordings for 78 patients with ADSD. General regression models were used to examine the relationship between overall voice quality and 15 variables that capture glottal geometry dynamics derived from the computer vision system. Two experts in ADSD independently rated voice quality for two separate voice tasks for every patient, yielding four different voice quality rating models. RESULTS: All four of the regression models exhibited positive correlations with clinical assessments of voice quality (R 2s = .30-.34, Spearman rho = .55-.61, all with p < .001). Seven to 10 variables were included in each model. There was high overlap in the variables included between the four models, and the sign of the correlation with voice quality was consistent for each variable across all four regression models. CONCLUSION: We found specific glottal geometry dynamics that correspond to voice quality in ADSD.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Importance: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. Objective: To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). Design, Setting, and Participants: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Main Outcomes and Measures: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Results: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). Conclusions and Relevance: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

Transoral Feminizing Chondrolaryngoplasty: Development and Deployment of a Novel Approach in 77 Patients.

Importance: Transgender patients who desire a gender-congruent neck contour may forego transcutaneous procedures due to the risk of neck scar stigmata related to such procedures. Objective: To describe the development and experience with the first 77 cases of a novel gasless transvestibular technique for gender-affirming surgery of the laryngeal prominence. Design, Setting, Participants: Video and narrative description of a novel surgical technique, and case series describing the consecutive first 77 patients to undergo transoral chondrolaryngoplasty (TCLP) at a quaternary transgender referral center. Results: Between November 2019 and April 2022, 77 patients underwent the novel surgery of TCLP. Median follow-up was 8.74 months (range: 1-30 months). Four patients suffered surgical complications (two laryngotomy, two skin necrosis), and three patients requested revision surgery. Conclusions and Relevance: TCLP is reported in the largest published series to date offering hidden incision for gender-affirming care. With further prospective outcome investigations, TCLP may prove to be a reliable approach of performing chondrolaryngoplasty while avoiding visible neck incisions.

Incidence and Outcomes of Laryngeal Complications Following Adult Cardiac Surgery: A National Analysis.

Laryngeal complications (LCs) following cardiac operations contribute to increased morbidity and resource utilization. Using a nationally representative cohort of cardiac surgical patients, we characterized the incidence of LC as well as its associated clinical and financial outcomes. All adults undergoing coronary artery bypass grafting and/or valvular operations were identified using the 2010-2017 Nationwide Readmissions Database. International Classification of Diseases 9th and 10th Revision diagnosis codes were used to identify LC. Trends were analyzed using a rank-based, non-parametric test (nptrend). Multivariable linear and logistic regressions were used to evaluate risk factors for LC, and its impact on mortality, complications, resource use and 30-day non-elective readmissions. Of an estimated 2,319,628 patients, 1.7% were diagnosed with perioperative LC, with rising incidence from 1.5% in 2010 to 1.8% in 2017 (nptrend < 0.001). After adjustment, female sex [adjusted odds ratio 1.08, 95% confidence interval (CI) 1.04-1.12], advancing age, and multi-valve procedures (1.51, 95% CI 1.36-1.67, reference: isolated CABG) were associated with increased odds of LC. Despite no risk-adjusted effect on mortality, LC was associated with increased odds of pneumonia (2.88, 95% CI 2.72-3.04), tracheostomy (4.84, 95% CI 4.44-5.26), and readmission (1.32, 95% CI 1.26-1.39). In addition, LC was associated with a 7.7-day increment (95% CI 7.4-8.0) in hospitalization duration and $24,200 (95% CI 23,000-25,400) in attributable costs. The present study found LC to be associated with increased perioperative sequelae and resource utilization. The development and application of active screening protocols for post-surgical LC are warranted to increase early detection and reduce associated morbidity.

Flexible Bronchoscopy Simulation as a Tool to Improve Surgical Skills in Otolaryngology Residency.

OBJECTIVE: To evaluate the benefits of simulation to teach flexible bronchoscopy. STUDY DESIGN: A prospective cohort study to assess the bronchoscopic skills of residents in an otolaryngology training program using a commercially available bronchoscopy simulator. SETTING: Tertiary care otolaryngology residency program. METHODS: Thirty-two otolaryngology residents and 4 expert faculty across 2 academic institutions were assessed on 3 flexible bronchoscopy tasks: diagnostic bronchoscopy, foreign body removal, and tracheal lesion biopsy. Performance was evaluated with a modified version of the validated Bronchoscopy Skills and Tasks Assessment Tool. At 1 of the 2 academic institutions, an additional tool was implemented to evaluate the simulator. RESULTS: There was a correlation between postgraduate training year and time taken to complete tasks, including bronchoscopy, foreign body extraction, and passing through the glottis (P < .001, P = .04, and P < .01, respectively). There was a significant difference between residents and faculty laryngologists for a range of skills and tasks, including percentage of time in middle lumen, contact with bronchial walls, inadvertent esophagus entry, and biopsy of healthy tissue (P < .001, P = .003, P < .001, and P < .001). Additionally, increasing postgraduate level was correlated with a higher percentage of time in the center of the lumen and reduced time to task completion (P = .05 and P < .001). Of 32 residents, 20 evaluated the simulator on its realism, with an average score of 4.1 of 5. CONCLUSION: The commercially available flexible bronchoscopy simulator provides a valid assessment of bronchoscopic skill and is a useful tool for practicing bronchoscopy in a safe, controlled environment. LEVEL OF EVIDENCE: Individual cohort study.

Single-port transoral robotic surgery hypopharyngectomy.

Transoral robotic surgery (TORS) is an established treatment for many subsites of Head and Neck cancer. With the improved flexibility and access of the single-port (SP) robotic system, tumors within the distal upper aerodigestive tract can now be reached and successfully treated with all the published advantages of transoral endoscopic surgery. Here in we offer the first published surgical technique for SP TORS for resectable hypopharyngeal carcinoma. The video presented demonstrates many important aspects utilizing the enhanced robotic system, including adjustments of the semi-flexible endoscope and use of the third transoral surgical instrumentation. As previously reported, TORS hypopharyngectomy should be considered for resectable tumors to improve upon the deleterious effects of open surgical resection or chemoradiation therapy.

Adverse Events in Hypoglossal Nerve Stimulator Implantation: 5-Year Analysis of the FDA MAUDE Database.

OBJECTIVE: Use of hypoglossal nerve stimulator implantation has dramatically improved the surgical treatment of multilevel airway collapse during obstructive sleep apnea (OSA). Understanding causes of adverse events and their impact on patients undergoing stimulator implantation will help improve patient preparation and surgical practices to avoid future complications. STUDY DESIGN: This study is a retrospective review of the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, a publicly available voluntary reporting system. SETTING: National patient event database. METHODS: The MAUDE database was searched for reports associated with the terms "hypoglossal nerve stimulator" and "Inspire," being the only currently FDA-approved system for upper airway stimulation for OSA. All records were searched with the events limited in dates between May 2014 and September 2019. RESULTS: A total of 132 patient reports were identified over the 5-year inclusion period, containing 134 adverse events. The reported adverse events resulted in 32 device revision procedures as well as 17 explantations. Device migration and infection were 2 of the most commonly reported adverse events. Complications not witnessed in previous large-scale clinical trials included pneumothorax, pleural effusion, and lead migration into the pleural space. CONCLUSION: Previous data have demonstrated hypoglossal nerve stimulator implantation results in reliable OSA improvement. However, a number of technical difficulties and complications still exist during the perioperative period, which should be communicated to patients during the surgical consent process.