Faculty Bibliography

PURPOSE/OBJECTIVE:Laser surgical management of human papillomavirus (HPV)-related disease, such as recurrent respiratory papillomatosis (RRP), in the upper aerodigestive tract generates surgical smoke, which may represent a source of occupational viral exposure for laryngeal surgeons, phoniatricians, anesthesia providers and scrub nurses. Despite growing awareness, protective measures remain inconsistently implemented. This study aimed to develop an evidence-informed clinical consensus statement (CCS) to guide occupational HPV risk management in laryngology. METHODS:A modified Delphi consensus process was conducted under the auspices of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP). A panel of 26 international experts undertook three rounds of voting on 18 statements across five domains: definitions and risk perception, personal protective measures, smoke evacuation and ventilation, preventive vaccination, and areas for further research. RESULTS:All panellists completed all three rounds. Of the 18 statements, one reached strong consensus, seven reached consensus, one reached near consensus and six did not reach consensus. Three statements were merged across rounds. Key areas of consensus included the recognition of surgical smoke as a potential occupational HPV exposure risk, the inadequacy of standard surgical masks, the importance of offering HPV vaccination to healthcare workers with potential occupational exposure, alongside areas for further research. CONCLUSION/CONCLUSIONS:This joint ELS and UEP CCS represents the first internationally coordinated effort to address occupational HPV exposure in laryngology. While consensus was reached in several key areas, the findings underscore the need for targeted research and greater consistency in protective measures, educational provision and regulatory frameworks.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Concurrent chemoradiotherapy (CCRT) is an effective treatment for various head and neck cancers; however, CCRT can result in significant swallowing impairment, presumably due largely to dysfunction of the muscles of swallowing, which are within the field of radiation. This translational study examines the mechanisms underlying CCRT-induced muscle dysfunction using (1) a rat model of CCRT and (2) analysis of archival human specimens. METHODS:131 Sprague Dawley rats were divided into experimental and control groups. Experimental rats received cisplatin and 5-fluorouracil intravenously, followed by 7 Gray radiation daily for 5 days. Rats were further split into three time points: acute (2 weeks), intermediate (5 months), and long-term (10 months), at which time tissue was harvested for analysis. Human samples included preexisting CCRT-treated and age- and sex-matched control muscle samples from head and neck cancer patients. Quantitative analyses of Paired Box Homeotic Gene 7-positive cells (Pax7 in rats; PAX7 in humans), fibrosis, muscle fiber size, and neuromuscular junctions were conducted and compared between groups in both rats and humans. RESULTS:Analysis demonstrated a significant decline in the percent of Pax7/PAX7-positive cells (a marker of muscle stem cells) after CCRT in both rats and humans, increased collagen percent, and decreased muscle percent in rats at 10 months. CCRT was associated with significantly reduced muscle fiber size in human specimens. Neuromuscular junction presence and morphology in rats were not affected. CONCLUSION/CONCLUSIONS:This translational study demonstrates significant alterations in head and neck muscles in both a rat model and human specimens from subjects exposed to CCRT. LEVEL OF EVIDENCE/METHODS:NA.

OBJECTIVE:To develop an expert consensus statement (ECS) on the diagnosis and treatment of refractory chronic cough (RCC) in adults. RCC was defined as cough lasting longer than 8 weeks and refractory to standard management of pulmonary, gastrointestinal, sinonasal, and medication-induced etiologies. METHODS:An expert panel of otolaryngologists used published consensus statement methodology to develop statements guiding the diagnosis and management of RCC from an otolaryngologic perspective. A modified Delphi method was used to iteratively select, eliminate, and refine statements based upon accepted methodology until consensus was achieved. RESULTS:Three iterative Delphi surveys were performed with discussion rounds between each of the voting sessions. Twenty-seven statements met consensus while six statements did not. The clinical statements were grouped into 9 categories: operational definition, pathophysiology, assessment of prior work-up, phenomenology and symptomatology, four treatment categories (neuromodulators, superior laryngeal nerve blocks, behavioral cough suppression, and emerging treatments), and overall treatment approaches. CONCLUSION/CONCLUSIONS:The panel reached consensus for 27 statements related to the diagnosis and treatment of adults with RCC from an otolaryngologic perspective. These statements may be used to standardize evaluation and improve quality of care, while also identifying areas for future investigation in the management of RCC.

OBJECTIVE:With regulatory approval of HPV-specific immunotherapy for recurrent respiratory papillomatosis (RRP) and growing experience with systemic bevacizumab, a management algorithm incorporating these medical treatments is warranted. DATA SOURCES AND METHODS/METHODS:RRP Foundation (RRPF) Key Opinion Leaders offer a proposed management algorithm for adults with RRP considering published literature and commercial drug availability. RESULTS:Preventative HPV vaccination should be considered for all patients. Determination of HPV type and pulmonary imaging are important for contemporary RRP patient care and assist in decision making. Risks and benefits of papilloma debulking as needed versus medical management of RRP must be deliberated on a patient case-by-case basis. HPV-specific immunotherapy that induces an HPV-specific T cell response to target the underlying HPV infection that is the cause of RRP is safe, offers the possibility of durable disease control following a short treatment course and is the recommended first-line medical treatment for patients who wish to avoid the risks of repeat procedural management. Papilloma disease control with systemic bevacizumab, which carries defined risks and must be continued for clinical benefit is the recommended second-line medical treatment for patients who do not achieve a complete response with immunotherapy and wish to continue medical management. For patients who elect to be treated with debulking procedures as needed, use of locally-administered adjuvant should be considered. CONCLUSION/CONCLUSIONS:This proposed management algorithm from the RRPF serves as a contemporary resource and information guide for adult patients with RRP and their physicians considering treatment options.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:This study assessed the vocal health of performers returning to full-time performance after the COVID-19 pandemic shutdown and investigated how differences in voice usage, exposure to voice care professionals, and vocal pathology before and during the pandemic contributed to variability in self-perceived and instrumental vocal outcome measures. STUDY DESIGN/METHODS:This was a prospective, case-control observational study conducted at a single outpatient site. METHODS:Twenty-two patients, 11 cases and 11 controls, were enrolled for the study. All participants were full-time singing professionals prior to the COVID-19 pandemic. Cases were recruited from patients presenting to a tertiary care voice center for vocal or pharyngeal complaints. Controls were healthy volunteers recruited from the general population of professional singers in the surrounding metropolitan area. All participants provided responses to the Voice Handicap Index-10, Evaluation of Ability to Sing Easily, and Laryngopharyngeal Measure of Perceived Sensation validated questionnaires as well as a study survey with questions regarding vocal use and history prior to and during the pandemic. All participants underwent instrumental acoustic and videostroboscopic voice evaluations. RESULTS:Cases had poorer outcome measures overall and were more likely to report their voices were worse at study enrollment when compared to their prepandemic perception (P = 0.027). Cases tended to be older and less likely to have pursued alternative employment during the pandemic that involved increased speaking voice use (27% vs 55%), but these differences were not statistically significant. CONCLUSIONS:There was a variable response among performers to the prolonged hiatus from performing during the COVID-19 pandemic. Those with poorer outcomes tended to be older and may have used their voice less during the pandemic. These findings are consistent with detraining periods in the exercise physiology literature and support the construct of treating vocal performers as vocal athletes.

BACKGROUND/UNASSIGNED:) and intensity modulation), patient perception of their voice remains unexamined despite its clinical importance. This study aimed to characterize the relationship between patient-reported vocal tremor severity and acoustic voice outcomes at baseline and after botulinum toxin injections. METHOD/UNASSIGNED: RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:Participants reporting more severe vocal tremor demonstrated more aberrant acoustic voice outcomes. After botulinum toxin injection, substantial heterogeneity was observed in acoustic voice measures which varied based on patient perception of change. These preliminary, exploratory findings provide a foundation for future investigations to define meaningful change in this population.

OBJECTIVE:To evaluate the long-term safety and clinical effect of INO-3107 immunotherapy in adults with recurrent respiratory papillomatosis (RRP). METHODS:RRP-002 was a retrospective, observational extension study that followed patients enrolled in the 52-week RRP-001 study. Patients with moderate to severe juvenile or adult-onset RRP who had undergone ≥ 2 surgical interventions in the year preceding dosing were eligible for enrollment in RRP-001. Participants underwent surgical debulking within 14 days prior to initial dosing and then received INO-3107 on Day 0, Weeks 3, 6, and 9. Efficacy assessments during RRP-002 follow-up were the frequency of surgical interventions and alternative medication use. The safety evaluation included reported severe adverse events (SAEs). RESULTS:Twenty-eight (28) of 32 participants from the 52-week RRP-001 study were enrolled in RRP-002. The median follow-up time for RRP-002 was 1.8 years (range: 1.2-2.4 years) for a total median assessment time of 2.8 years (range: 1.0-3.5 years). There were no SAEs or long-term safety concerns identified. The mean number of surgeries was reduced from 4.1 in the pre-treatment period to 1.7 in the first year post-INO-3107 treatment (Year 1) to 0.9 in the second year (Year 2). The complete response rate (0 surgeries per year) increased from 28% (9/32) in Year 1 to 50% (14/28) in Year 2. CONCLUSION/CONCLUSIONS:INO-3107 is well tolerated and provides a continued clinical effect against HPV-6 and 11 RRP that results in further reduction of the surgical burden observed in Year 1. These data support the role of INO-3107 immunotherapy for adult patients with RRP. LEVEL OF EVIDENCE/METHODS:III.

OBJECTIVES/OBJECTIVE:) and PRO scores; (3) explore how changes across individual PROs align with changes in DIGEST pre- to six weeks post- surgery. METHODS:) pharyngeal total score and the DIGEST. PROs included the Bazaz Dysphagia Scale, the Eating Assessment Tool (EAT-10), the Swallowing Quality of Life Questionnaire (SWAL-QoL), and the Hospital for Special Surgery Dysphagia Index (HSS-DDI). RESULTS:Statistical models for all outcome measures revealed a significant effect of operative timepoint, indicating worse outcomes postoperatively. There were greater postoperative increases in point prevalence and incidence rates using PROs compared with DIGEST. Rates of clinically meaningful change were similar across PROs and DIGEST, but not consistently across the same individual cases. CONCLUSION/CONCLUSIONS:This study highlights the difference between physical function and patient experience, suggesting the presence or absence of dysphagia symptoms may not correspond with observed physical impairments after ACDF. LEVEL OF EVIDENCE/METHODS:Level III.

OBJECTIVE:Surgical treatment of recurrent respiratory papillomatosis (RRP) has been shown to aerosolize human papillomavirus (HPV), putting healthcare workers at risk for exposure, infection, and disease. Knowledge of HPV infection risk among otolaryngologists who treat HPV-related diseases is limited. We sought to characterize the prevalence of oral HPV infection in otolaryngologists treating RRP. METHODS:This observational cohort study enrolled otolaryngologists at a national meeting. Participants completed a survey concerning HPV vaccination, disease history, and practice techniques for patients with RRP. An oral rinse was collected from participants; DNA was extracted and analyzed using commercially available kits. RESULTS:laser (N = 78), microdebrider (N = 80), and cold steel (N = 21). Oral rinses from three participants (2.2%) tested positive for HPV, including Subtypes 6 (N = 2) and 16 (N = 1). All three were male with no history of HPV vaccination. CONCLUSION/CONCLUSIONS:Otolaryngologists treating HPV-related diseases do not seem to be at a higher risk of HPV infection compared to the general adult population. Vaccination, the use of N95 masks, and minimizing aerosol-generating techniques are likely protective for healthcare workers dealing with HPV-related conditions.