Skip to main navigation menu Skip to main content Skip to site footer
Brazilian Journal of Clinical Medicine and Review

Original research

Vol. 4 No. 1 (2026): January/December - 2026

Recurrent Respiratory Papillomatosis: Current Insights into Epidemiology, Pathogenesis, and Emerging Therapeutic Strategies

DOI
https://doi.org/10.52600/2965-0968.bjcmr.2026.4.1.bjcmr45
Submitted
October 8, 2025
Published
2025-11-06

Abstract

Recurrent respiratory papillomatosis (RRP) is a benign, HPV 6/11-driven airway disease with frequent recurrences, often requiring multiple surgeries and imposing significant clinical and economic burdens. This narrative review synthesizes evidence from 2010–2025 on epidemiology, pathogenesis, clinical features, and therapies, emphasizing advances like bevacizumab, immune checkpoint inhibitors, and gene therapy (PRGN-2012, announced for FDA approval as Papzimeos™ on August 14, 2025). A structured literature search in PubMed, Scopus, and Web of Science identified 26 studies (clinical trials, cohorts, reviews). Key findings: HPV vaccination reduced juvenile RRP (JoRRP) incidence by >90% in vaccinated populations (e.g., Australia). Bevacizumab prolongs surgery-free intervals (up to 85% response rate systemically), while PRGN-2012 achieved a 51% complete response (no surgery for ≥12 months) with sustained benefits >2 years and mild adverse events, pending confirmation in peer-reviewed publications. INO-3107 reduced mean surgeries from 4.1 to 0.9 over two years, with an 86% overall response rate (ORR) in Year 2. Traditional adjuvants like cidofovir remain relevant in low-resource settings. Multimodal strategies (surgery, anti-angiogenics, immunotherapy) shift toward disease modification. Enhanced vaccination and biomarker research are crucial for global control.

References

  1. Derkay CS, Wiatrak B. Recurrent respiratory papillomatosis: A review. Laryngoscope. 2008;118(7):1236–1247.
  2. Preciado D, Zalzal G. RRP: Current concepts and management. Curr Opin Otolaryngol Head Neck Surg. 2012;20(6):553–558.
  3. Carifi M, Napolitano D, Morandi M, et al. Recurrent respiratory papillomatosis: Current and future perspectives. Ther Clin Risk Manag. 2015;11:731–738.
  4. Rosen CA, Bryson PC. Indications for surgery and adjuvant therapy in RRP. Curr Opin Otolaryngol Head Neck Surg. 2018;26(3):162–167.
  5. Norberg SM, et al. PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: A pivotal phase 1/2 clinical trial. Lancet Respir Med. 2024;13(4):318–326.
  6. Novakovic D, Cheng ATL, et al. Impact of HPV vaccination on RRP incidence: A population-based study. JAMA Otolaryngol Head Neck Surg. 2023;149(2):125–133.
  7. Dedo HH, Yu KC. Adult-onset RRP: Epidemiology and natural history. Ann Otol Rhinol Laryngol. 2001;110(6):502–509.
  8. Armstrong LR, et al. Incidence and prevalence of RRP in the United States. Laryngoscope. 2010;120(9):1759–1766.
  9. Garland SM, et al. Global impact of HPV vaccination. Vaccine. 2016;34(52):6413–6420.
  10. Marsico M, et al. Economic burden of RRP. Laryngoscope. 2014;124(12):2820–2826.
  11. Gerein V, et al. HPV type 11 predicts aggressive RRP. Eur Arch Otorhinolaryngol. 2005;262(6):512–516.
  12. Stanley M. Pathogenesis of HPV infection. J Clin Virol. 2010;49(4):S7–S15.
  13. Albers A, et al. E6/E7 oncogene expression in RRP. J Med Virol. 2006;78(10):1434–1443.
  14. Bonagura VR, et al. Immune dysfunction in RRP. Clin Exp Immunol. 2010;161(3):408–416.
  15. Vambutas A, Bonagura VR. Natural immunity in RRP. Curr Opin Otolaryngol Head Neck Surg. 2021;29(6):435–442.
  16. San Giorgi MRM, et al. Cytokine profiles in RRP. Clin Otolaryngol. 2016;41(5):549–557.
  17. Iftner A, et al. Genetic predisposition to RRP. PLoS One. 2012;7(12):e49236.
  18. Van den Hoogen FJ, et al. Genomic landscape of HPV in RRP. Tumour Virus Res. 2024;17:200291.
  19. Simo R, et al. Cidofovir and interferon therapy outcomes. Head Neck. 2013;35(7):1019–1025.
  20. Yilmaz T, et al. dsRNA-induced interferon therapy in refractory RRP. Acta Otolaryngol. 2019;139(7):640–646.
  21. Best SR, et al. Bevacizumab in RRP: Mechanistic insights. Laryngoscope. 2012;122(10):2146–2152.
  22. Zeitels SM, et al. Systemic bevacizumab for aggressive RRP. Ann Otol Rhinol Laryngol. 2022;131(10):1145–1152.
  23. Maturo S, Hartnick C. Intralesional bevacizumab outcomes in JoRRP. Otolaryngol Head Neck Surg. 2023;169(2):345–353.
  24. Young DL, et al. HPV vaccination as adjuvant therapy in RRP. Laryngoscope. 2022;132(3):567–575.
  25. Ventola CL. Immunotherapeutic advances in HPV disease. Pharm Ther. 2024;49(1):42–55.
  26. Dooling KL, et al. Immunotherapy and checkpoint blockade in RRP. Cancer Immunol Res. 2024;12(5):622–631.
  27. U.S. Food and Drug Administration. FDA Approves First Immunotherapy for Recurrent Respiratory Papillomatosis. 2025.
  28. Precigen, Inc. Precigen Announces Groundbreaking Pivotal Study Data for PRGN-2012. 2024.
  29. Bagley AF, et al. DNA Immunotherapy (INO-3107) Results in Long-Term Surgery Reduction in Recurrent Respiratory Pap-illomatosis. Laryngoscope. 2025; doi:10.1002/lary.32416.
  30. World Health Organization. Human Papillomavirus (HPV) vaccination coverage. 2025.