The Laryngoscope V C 2017 The American Laryngological, Rhinological and Otological Society, Inc. Laryngeal Distribution of Recurrent Respiratory Papillomatosis in a Previously Untreated Cohort Peter A. Benedict, BA; Ryan Ruiz, MD; MiJin Yoo, MD ; Avanti Verma, MD; Omar H. Ahmed, MD; Binhuan Wang, PhD; Gregory R. Dion, MD; Andrew Voigt; Albert Merati, MD; Clark A. Rosen, MD; Milan R. Amin, MD; Ryan C. Branski, PhD Objectives/Hypothesis: To describe the distribution of recurrent respiratory papillomatosis (RRP) lesions across 21 laryngeal anatomic regions in previously untreated patients at initial presentation to provide insight regarding the natural history of RRP. Study Design: Multi-institutional, retrospective case series. Methods: Initial laryngoscopic examination videos of 83 previously untreated patients with adult-onset RRP were reviewed. Papilloma locations were recorded using a 21-region laryngeal schematic. Multivariate analyses by anatomic subsite were conducted for the entire population and for subgroups stratified by sex, age, and proton pump inhibitor (PPI) usage. Heat maps were generated, hierarchically color coding the anatomic distribution of disease. Results: In this cohort, RRP was most likely to occur on the true vocal folds (TVFs) and anterior commissure (P <.0001, odds ratio [OR]: 7.02); within the TVFs, the membranous vocal folds (MVFs) were most likely to be affected (P <.0001, OR: 3.56). The cohort was predominantly male (80.7%); males had a higher average number of affected sites (P 5.005) and were more likely to have lesions in any laryngeal subsite (P <.0001, OR: 2.88,) compared to females. PPI users were more likely than nonusers to have disease in any laryngeal subsite (P 5.0037, OR: 1.62), particularly in the posterior and subglottic regions (P 5.0061, OR: 2.53). Age was not correlated with lesion prevalence or distribution. Conclusions: In untreated patients presenting to three laryngology clinics, the MVFs were most likely to be affected by RRP. Males had more anatomic sites affected by papilloma than females. The influence of PPI use on RRP distribution war- rants further investigation. Key Words: Recurrent respiratory papillomatosis, distribution, prevalence, larynx, heat map, gender, proton pump inhibitor. Level of Evidence: 4. Laryngoscope, 00:000–000, 2017 INTRODUCTION Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV) infection. RRP is characterized by benign, exophytic neo- plasms of the aerodigestive tract. These lesions show a strong predilection for the larynx, so much so that the disorder is frequently referred to as laryngeal or glottal papillomatosis. 1,2 Although RRP is a relatively rare dis- ease, with an incidence of approximately 1.8 per 100,000 adults in the United States, it is the most common benign tumor of the larynx. 3 Clinically, patients with RRP typically present with altered voice, but cough and dyspnea are also common. In addition to the recurrent nature of RRP and its negative impact on voice quality, the disease may progress to life-threatening airway obstruction. 4 RRP follows an unpredictable course, although some patients experience spontaneous remis- sion or recover after a single laryngeal procedure. For many, RRP is a relapsing and morbid disease. To date, the distribution of RRP lesions within the larynx has been reported only for cohorts in which some or all patients received treatment prior to analyses. Because of the poorly understood interplay between treatment and recurrence, these studies likely fail to capture the true natural distribution and progression of disease. For instance, following surgical or ablative treatment, lesions may potentially persist in regions more technically challenging to access, or may recur in regions more conducive to postprocedural HPV survival. Additionally, treatment itself may induce iatrogenic From the NYU Voice Center, Department of Otolaryngology–Head and Neck Surgery (P .A.B., R.R., A.VERMA, O.H.A., G.R.D., A.VOIGT, M.R.A., R.C.B.) and Department of Population Heath, Division of Biostatistics (B.W.), New York University School of Medicine, New York, New York; Depart- ment of Otolaryngology–Head and Neck Surgery (M.J., A.M.), University of Washington School of Medicine, Seattle, Washington; Department of Otolaryngology–Head and Neck Surgery (G.R.D.), Brooke Army Medical Center, Fort Sam Houston, Texas; and the University of Pittsburgh Voice Center, Department of Otolaryngology (C.A.R.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication May 22, 2017. Presented at the 138th Annual Meeting of the American Laryngo- logical Association at the Combined Otolaryngology Spring Meetings, San Diego, California, U.S.A., April 26–30, 2017. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Ryan C. Branski, PhD, NYU Voice Center, 345 East 37th Street, Suite 306, New York, NY 10016. E-mail: ryan. branski@nyumc.org DOI: 10.1002/lary.26742 Laryngoscope 00: Month 2017 Benedict et al.: Laryngeal Distribution of RRP 1