A Consensus Statement on the Administration of Systemic Bevacizumab in Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: To provide detailed guidance on the administration of systemic bevacizumab in patients with recurrent respiratory papillomatosis (RRP) based on a detailed review of the scientific literature and a consensus of experts with real-world clinical experience. METHODS: A bevacizumab consensus working group (N = 10) was composed of adult and pediatric otolaryngologists, adult and pediatric oncologists, and a representative from the RRP Foundation (RRPF), all with experience administering systemic bevacizumab in patients with RRP. After extensive review of the medical literature, a modified Delphi method-based survey series was utilized to establish consensus on the following key areas: clinical and patient characteristics ideal for treatment candidacy, patient perspective in treatment decisions, treatment access, initial dosing, monitoring, guidelines for tapering and discontinuation, and reintensifying therapy. RESULTS: Seventy-nine statements were identified across nine critical domains, and 45 reached consensus [clinical benefits of bevacizumab (3), patient and disease characteristics for treatment consideration (7), contraindications for treatment (3), shared decision-making (incorporating the patient perspective) (5), treatment access (3), initial dosing and administration (8), monitoring (7), tapering and discontinuation (6), and reintensification (3)]. CONCLUSION: This consensus statement provides the necessary guidance for clinicians to initiate systemic administration of bevacizumab and represents a potential paradigm shift toward nonsurgical treatment options for patients with RRP. LEVEL OF EVIDENCE: 5 Laryngoscope, 2024.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution's Experience.

OBJECTIVES: Medical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP. METHODS: A retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented. RESULTS: Of the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile-onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new-onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%). CONCLUSION: Systemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial-to-stable response. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3253-3259, 2024.

Profiling of VEGF Receptors and Immune Checkpoints in Recurrent Respiratory Papillomatosis.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is caused by human papilloma virus (HPV) infection of the aerodigestive tract that significantly impacts quality-of-life including the ability to communicate and breathe. Treatment was traditionally limited to serial ablative procedures in the O.R. with possible local adjuvant therapy, but new systemic therapies, such as Vascular endothelial growth factor (VEGF) inhibitors, are showing significant promise. This study aims to determine whether rationale exists for combination therapeutic approaches using VEGF inhibitors and/or immune checkpoint blockade. METHODS: Using fresh specimens from the O.R., we performed flow cytometry on papilloma, normal adjacent tissue, and blood. Papilloma and surrounding tissue were examined for expression of PD-L1, PD-L2, Galectin-9, VEGFR2, and VEGFR3. CD8+ and CD4+ T cells were assayed for expression of PD-1, TIGIT, LAG3, and TIM3. RESULTS: Our data shows that papilloma tissue exhibits significantly higher levels of PD-L1 and PD-L2 compared to adjacent tissue. Elevated levels of the VEGF receptor VEGFR3 were also observed in papilloma tissue. When examining T cells within the papilloma, elevated PD-1 and TIGIT expression was observed on CD8+ T cells, while levels of PD-1, TIGIT, and TIM3 were elevated on CD4+ T cells compared to PBMCs. Heterogenous marker expression was observed between individuals. CONCLUSIONS: Our analysis shows that RRP tissue shows elevated levels of multiple immune check point targets and VEGFR3, with varied patterns unique to each papilloma patient. Some of these immune checkpoint markers already have novel immunotherapies available or in development, providing molecular rationale to offer these systemic treatments to selected patients affected by RRP alongside VEGF inhibitors. Laryngoscope, 134:2819-2825, 2024.

Efficacy of Systemic Bevacizumab for Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

OBJECTIVES: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. METHODS: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. RESULTS: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. CONCLUSION: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:577-581, 2024.

Tracheostomy-related durable medical equipment: Insurance coverage, gaps, and barriers.

PURPOSE: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. MATERIALS AND METHODS: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. RESULTS: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 ± 10 min, with an average of 2 ± 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 ± 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. CONCLUSIONS: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and low-quality information. Further research is necessary to evaluate patient outcomes.

Factors Associated with Iatrogenic Laryngeal Injury in Recurrent Respiratory Papillomatosis.

OBJECTIVE: To describe iatrogenic laryngeal injury and identify its risk factors in recurrent respiratory papillomatosis (RRP) patients receiving surgical care. STUDY DESIGN: Case-control. SETTING: Tertiary care academic hospital in a metropolitan area. METHODS: Charts of patients with RRP seen at our institution from January 2002 to December 2022 were reviewed. Patients were separated into 2 cohorts based upon whether they experienced any form of iatrogenic laryngeal injury-including anterior commissure synechiae, vocal cord scar, reduced vocal fold pliability, vocal fold motion impairment, and glottic and/or subglottic stenosis. Adjusted logistic regressions were performed to identify factors associated with iatrogenic laryngeal injury. RESULTS: Of 199 RRP patients, 133 (66.8%) had identifiable iatrogenic laryngeal injury. The most common injuries were anterior commissure synechiae (n = 67; 50.4%) and reduced vocal fold pliability (n = 54; 40.6%). On a multivariate logistic regression, patients with diabetes mellitus (adjusted odds ratio [aOR] [95% confidence interval [CI]]: 2.99 [1.02, 8.79]; P = .04) and who received at least 10 surgeries lifetime (aOR [95% CI]: 14.47 [1.70, 123.19]; P = .01) were at increased risk for iatrogenic laryngeal injury, whereas receiving less than 5 surgeries (aOR [95% CI]: 0.21 [0.09, 0.51]; P < .001) was found to be protective. When treating the lifetime number of surgeries as a continuous variable, a greater number of surgeries was a significant risk factor for iatrogenic laryngeal injury (aOR [95% CI]: 1.32 [1.14, 1.53]; P < .001). CONCLUSION: These results suggest the importance of strict glucose control for diabetic patients receiving RRP surgical care, and emphasize the clinical need to identify medical therapies to decrease RRP surgical frequency for patients.

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis.

OBJECTIVE: To evaluate the safety, immunogenicity, and efficacy of INO-3107, a DNA immunotherapy designed to elicit targeted T-cell responses against human papillomavirus (HPV) types 6 and 11, in adult patients with recurrent respiratory papillomatosis (RRP; NCT04398433). METHODS: Eligible patients required ≥2 surgical interventions for RRP in the year preceding dosing. INO-3107 was administered by intramuscular (IM) injection followed by electroporation (EP) on weeks 0, 3, 6, and 9. Patients underwent surgical debulking within 14 days prior to first dose, with office laryngoscopy and staging at screening and weeks 6, 11, 26, and 52. Primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included frequency of surgical interventions post-INO-3107 and cellular immune responses. RESULTS: An initial cohort of 21 patients was enrolled between October 2020 and August 2021. Fifteen (71.4%) patients had ≥1 TEAE; 11 (52.4%) were Grade 1, and 3 (14.3%) were Grade 3 (none treatment related). The most frequently reported TEAE was injection site or procedural pain (n = 8; 38.1%). Sixteen (76.2%) patients had fewer surgical interventions in the year following INO-3107 administration, with a median decrease of 3 interventions versus the preceding year. The RRP severity score, modified by Pransky, showed improvement from baseline to week 52. INO-3107 induced durable cellular responses against HPV-6 and HPV-11, with an increase in activated CD4 and CD8 T cells and CD8 cells with lytic potential. CONCLUSION: The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3087-3093, 2023.

Factors Associated With Loss of Follow-Up in Transgender Patients Receiving Vocal Therapy.

OBJECTIVES: Optimal vocal care for transgender patients necessitates regular follow-up. Factors associated with loss of follow-up in voice patients have never been investigated. In this study, we report a case series of transgender patients seeking vocal care at our institution and compare those who were and were not lost to follow-up. METHODS: Charts of transgender patients diagnosed with gender dysphoria who sought vocal care at our institution from January 2018 through May 2022 were reviewed. A chronological timeline of each patient's care at our vocal clinic was recorded. Loss of follow-up was defined as instances in which patients were not yet satisfied with their vocal outcomes and expressed interest in scheduling a subsequent visit but had not yet done so. Logistic regressions were performed to identify factors associated with loss of follow-up. RESULTS: Of 73 patients identified, 59 (80.8%) were assigned male at birth, and 72 (98.6%) were non-Hispanic White. Loss of follow-up occurred in 35 (47.9%) patients. Patients who received vocal surgery were significantly less likely to be lost to follow-up (OR: 0.16 (0.03, 0.79); p = 0.03). The availability of telemedicine options for vocal care was protective against loss of follow-up (OR: 0.09 (0.02, 0.44); p = 0.003). Patients who received other non-voice gender-affirming treatments concomitant to their vocal care were more likely to be lost to follow-up (OR: 4.44 (1.35, 14.59); p = 0.01). CONCLUSION: Loss of follow-up in transgender patients receiving vocal care is common. Providing telemedicine options and encouraging patients to complete vocal care prior to or after receiving other non-voice gender-affirming treatments may help increase rates of follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3061-3067, 2023.

Posterior Glottic Injury Following Prolonged Intubation in COVID-19 Patients.

OBJECTIVE: The objective of this study was to characterize the risk factors for posterior glottic injury (PGI) in patients with coronavirus disease 2019 (COVID-19) who underwent prolonged intubation. STUDY DESIGN: This was a case-control study designed to assess the risk factors associated with development of PGI in COVID-19 patients who underwent prolonged intubation. SETTING: This single-center study was conducted at a tertiary care academic hospital in a metropolitan area. METHODS: We retrospectively reviewed patients who underwent prolonged intubation (≥7 days) for COVID-19 and compared those with PGI to those without. Patient demographics, comorbidities, and intubation characteristics were compared. Factors associated with PGI development among COVID-19 patients were assessed using multivariate regression. RESULTS: We identified 56 patients who presented with PGI following prolonged intubation for COVID-19 and 60 control patients who underwent prolonged intubation for COVID-19 but did not develop PGI. On univariate analyses, the number of reintubations due to failed extubation efforts was significantly associated with development of PGI (odds ratio [OR], 2.9; 95% CI, 1.4-6.2). On multivariate analyses, patients with cardiovascular disease (OR, 3.3; 95% CI, 1.2-9.0); non-COVID-19 respiratory illnesses, which included obstructive sleep apnea and asthma (OR, 5.9; 95% CI, 2.0-17.8); and diabetes mellitus (OR, 11.6; 95% CI, 3.7-36.6) were more likely to develop PGI. CONCLUSION: Our results represent the largest case-control study investigating risk factors for PGI in the setting of prolonged intubation specific to COVID-19. Our study suggests a significant role of comorbidities associated with poor wound healing with development of PGI.

Recurrent Respiratory Papillomatosis: Quality of Life Data from an International Patient Registry.

OBJECTIVES: Quality of life studies in recurrent respiratory papillomatosis (RRP) have traditionally relied upon clinician-designed survey instruments. This study's objective is to report quality of life outcomes from a patient-designed questionnaire. METHODS: Patients who provided health information and completed a quality of life questionnaire were identified from the RRPF-CoRDS patient registry. Demographic, clinical, and quality of life measures were collected. Means and standard deviations were calculated for continuous data, and frequencies and percentages were calculated for categorical data. Outcomes for patients with juvenile-onset RRP (JORRP) and adult-onset RRP (AORRP) were compared using Student's t-tests for continuous data and χ2 analyses for categorical data. RESULTS: Seventy-three patients with RRP were identified (JORRP: 32; AORRP: 41). Common clinical symptoms included raspy voice (78.1%) and dyspnea (61.6%). The majority (97.3%) of patients reported feeling debilitated by their diagnosis, and 94.5% of patients reported avoiding participation in career and/or social activities due to their voice quality. Due to their RRP, 65.7% reported missing at least five work days each month. Social anxiety was reported in 79.5% of patients, though only 28.8% of the cohort reported utilizing mental health services. The median (range) lifetime number of surgeries received was 20 (1 - 300). Most patients (57.5%) reported paying at least 5% of their annual income towards RRP-related medical care. CONCLUSION: RRP presents high mental and fiscal burden. Our results highlight data from a quality of life questionnaire designed by RRP patients, and may help to elucidate potential disconnects between what clinicians and RRP patients consider most impactful. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1919-1926, 2023.

The Geographic Distribution of Videolaryngostroboscopy in the United States.

PURPOSE: To study the geographic utilization of videolaryngostroboscopy (VLS) with the hypothesis that office-based voice care is unevenly distributed across the United States. MATERIALS AND METHODS: This is a cross-sectional database analysis of Medicare beneficiaries. The Centers for Medicare and Medicaid Services Provider Utilization and Payment Data Physician and Other Supplier Public Use File from 2012 to 2017 was analyzed to evaluate VLS utilization. VLS distribution was assessed by calculating the density of VLS in each of the 306 hospital referral regions (HRRs) nationally. Associations between VLS density and population demographics and health system factors were assessed using Pearson correlation and multivariate regression analyses. RESULTS: In total, 957,648 outpatient VLS were billed to Medicare part B between 2012 and 2017. The annual VLS density per HRR ranged from 0 to 38.2 per 1,000 enrollees. Pearson correlation revealed positive correlations between VLS density and number of Medicare enrollees (r = 0.2584, P < 0.001), income (r = 0.1913, P = 0.0008), education (r = 0.2089, P = 0.0002), and density of otolaryngologists (r = 0.1589, P = 0.0053) and medical specialists (r = 0.2326, P < 0.0001). A negative Pearson correlation was observed between VLS density and percent male (r = -0.1338, P = 0.0192) and Medicare mortality rate (r = -0.1628, P = 0.0043). On multivariate regression positive associations between VLS and number of Medicare enrollees (P = 0.002) and otolaryngologists (P = 0.049), and negative association with Medicare mortality rates (P = 0.032) remained significant. CONCLUSIONS: The distribution of office-based voice care varies widely across the country, even when analysis by HRR should have homogenized access to specialty care. Greater availability of VLS is seen in HRRs with more Medicare enrollees, greater density of otolaryngologists, and lower mortality rates.

Readability Analysis and Accessibility of Online Materials About Transgender Voice Care.

OBJECTIVE: To determine readability, understandability, and actionability of online health information related to transgender voice care. STUDY DESIGN: Review of online materials. SETTING: Academic medical center. METHODS: A Google search of "transgender voice care" was performed with the first 50 websites meeting inclusion criteria included. Readability was assessed using the Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), and the Simple Measure of Gobbledygook (SMOG). Understandability and actionability were measured by 2 independent reviewers using the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). Unpaired t tests were used to compare clinician- and patient-oriented sites, surgical and nonsurgical sites, and sites that discuss nonbinary indications for voice care. Analysis of variance was used to compare sites that discuss voice feminization, masculinization, both, or neither. RESULTS: Average scores across the cohort for FRES, FKGL, and SMOG were 43.77 ± 13.52, 12.14 ± 2.66, and 11.30 ± 1.93, respectively, indicating materials were above a 12th-grade reading level. PEMAT-P scores for understandability and actionability were 64.95% ± 15.78% and 40.55% ± 23.86%, respectively. Patient-oriented sites were significantly more understandable and actionable than clinician-oriented sites (P < .02). Websites that discussed only voice feminization were significantly more readable according to objective metrics (FKGL, SMOG) than websites that discussed both feminization and masculinization or those that did not differentiate care types (P < .05). CONCLUSION: Online information written about transgender voice care is written at a level above what is recommended for patient education materials. Providers may improve accessibility of transgender voice care by enhancing readability of online materials.

Prospective, Multi-Center Study of the Anatomic Distribution of Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Prospective, multi-institutional cohort study. METHODS: Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence. RESULTS: The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites. CONCLUSIONS: RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2403-2411, 2022.

Impact of human immunodeficiency virus status on laryngeal cancer survival and locoregional control.

OBJECTIVES: To compare long-term outcomes of laryngeal cancer (LC) in people living with HIV (PLWH) versus uninfected individuals and determine how clinical and viral factors-such as demographics, cancer stage, HIV viral load, and CD4 nadir-contribute to these outcomes. METHODS: This was a retrospective case-control study of 749 patients seen for LC at a single tertiary care center between 2003 and 2017. Of these, 22 had HIV at the time of LC diagnosis, and they were matched in a 1:4 ratio to uninfected controls based on sex, presence of smoking history, and age at cancer diagnosis. Kaplan-Meier survival curves and Cox proportional hazards models were constructed to identify overall and disease-free survival differences based on HIV status, as well as other clinical and viral factors. RESULTS: Compared to all uninfected individuals, PLWH were diagnosed with LC approximately 6 years younger (p = .013). 1-, 2-, and 5-year overall survival for PLWH were 86.4% (63.4%-95.4%), 77.3% (53.7%-89.9%), and 65.8% (40.8%-82.2%), respectively following LC diagnosis, and HIV was not significantly associated with overall (HR = 3.34 [0.59-18.79]) or disease-free survival (HR = 2.12 [0.71-6.36]). The incidence rate of locoregional recurrence among PLWH was 541 compared to 371 per 10,000 person-years in controls, which were not significantly different (p = .420). Furthermore, among PLWH, peak viral load and CD4 nadir were not associated with overall or disease-free survival. CONCLUSION: While previous work has shown that HIV is associated with elevated risk of LC, survival did not differ significantly between PLWH and uninfected individuals in this study. LEVEL OF EVIDENCE: 3.

Laryngeal disorders in people living with HIV.

OBJECTIVES: Several studies have shown that HIV infected individuals are at higher risk compared to the general population of developing non-AIDS defining conditions such as some types of cancer, kidney disease, liver disease and others. In this case-control study, we compared the incidence of laryngeal disorders between a treatment-seeking HIV-positive population and uninfected controls. We aimed to investigate whether there are any laryngeal disorders that are overrepresented in HIV-positive individuals. METHODS: This was a case-control study based on retrospective chart review, comparing the incidence of laryngeal, airway, and swallowing disorders in sixty-nine HIV positive individuals and 4178 HIV negative controls treated between January 1, 2016 and December 31, 2017, at the Johns Hopkins Voice Center. RESULTS: A majority of HIV-infected patients (59.4%) had at least one diagnosis belonging to the Vocal cord pathology category compared to 48.2% of controls (OR 1.57, p = 0.065). Compared to the entire treatment-seeking population, HIV patients were more likely to present with laryngeal cancer (15.9% vs. 3.4% in controls, OR 5.43, p < 0.001) and chronic laryngitis (17.4% vs. 4.2%, OR 4.79, p < 0.001). Fungal and ulcerative laryngitis were also overrepresented in HIV-positive individuals (OR 9.45, p < 0.001 and 6.29, p < 0.001, respectively). None of the diagnoses categorized as functional voice disorders, swallowing, or airway problems showed a significant difference between groups. Laryngeal papillomatosis, which is an HPV-dependent disease, had similar prevalence in both groups. CONCLUSIONS: Treatment-seeking HIV-positive patients presenting to a laryngology clinic suffer significantly more often from laryngeal squamous cell carcinoma as well as chronic, fungal, and ulcerative laryngitis compared to HIV-negative individuals. LEVEL OF EVIDENCE: 4.

Readability of Online Materials Related to Vocal Cord Leukoplakia.

OBJECTIVES: To assess readability and understandability of online materials for vocal cord leukoplakia. STUDY DESIGN: Review of online materials. SETTING: Academic medical center. METHODS: A Google search of "vocal cord leukoplakia" was performed, and the first 50 websites were considered for analysis. Readability was measured by the Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG). Understandability and actionability were assessed by 2 independent reviewers with the PEMAT-P (Patient Education Materials Assessment Tool for Printable Materials). Unpaired t tests compared scores between sites aimed at physicians and those at patients, and a Cohen's kappa was calculated to measure interrater reliability. RESULTS: Twenty-two websites (17 patient oriented, 5 physician oriented) met inclusion criteria. For the entire cohort, FRES, FKGL, and SMOG scores (mean ± SD) were 36.90 ± 20.65, 12.96 ± 3.28, and 15.65 ± 3.57, respectively, indicating that materials were difficult to read at a >12th-grade level. PEMAT-P understandability and actionability scores were 73.65% ± 7.05% and 13.63% ± 22.47%. Statistically, patient-oriented sites were more easily read than physician-oriented sites (P < .02 for each of the FRES, FKGL, and SMOG comparisons); there were no differences in understandability or actionability scores between these categories of sites. CONCLUSION: Online materials for vocal cord leukoplakia are written at a level more advanced than what is recommended for patient education materials. Awareness of the current ways that these online materials are failing our patients may lead to improved education materials in the future.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Laryngeal Pathologies and Their Associations With Mental Health Disorders.

OBJECTIVES: Mental health disorders are very common. Understanding their clinical manifestations in terms of voice and laryngeal disorders (VLD) is important because they constitute a significant proportion of all patients seen by otolaryngology-head and neck surgery. In this study, we examine different mental disorders (MDs) and their presenting symptoms and diagnoses of VLD. METHODS: Case series study, retrospective chart review of patients seen between January 2016 and December 2017 at the Johns Hopkins Voice Center. Diagnoses, demographic data, and comorbidities were collected. VLD were grouped into categories (laryngeal pathology, functional voice disorders, airway, swallowing, other) for statistical analysis. RESULTS: Of a total 4,249 patients, 836 patients (19.7%) suffered from at least one MD. Those patients presented more frequently with swallowing problems (24.9% of all diagnoses in MD compared to 21.2% in control group; adjusted odds ratio [aOR] 1.280, 95% confidence interval [CI] 1.107-1.480, P = .001) and less frequently with vocal cord pathology (30.9% of all diagnoses in MD compared to 33.9% in control group, aOR 0.793, 95% CI 0.694-0.907, P = .001). Patients suffering from depression had significantly increased odds for dysphagia (aOR 1.570, 95% CI 1.216-2.026, P = .001). VLD clinical presentation profile was created for every MD studied. CONCLUSION: Patients suffering from mental health disorders present more frequently with swallowing complaints, in particular for dysphagia. Awareness of this can guide appropriate referrals. Objective laryngeal findings are common in patients with substance abuse disorders. They should be screened with careful diagnostic laryngoscopy. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E231-E239, 2021.