The Efficacy and Safety of Systemic Treatment for Managing Recurrent Respiratory Papillomatosis: A Systematic Review...

Surgical treatment remains the cornerstone of recurrent respiratory papillomatosis (RRP) management; however, aggressive disease often requires frequent procedures with cumulative morbidity. Contemporary systemic options now include systemic bevacizumab and human papillomavirus (HPV)-specific immunotherapies, with immune checkpoint inhibition under investigation. We systematically reviewed the efficacy and safety of systemic therapies for juvenile- and adult-onset RRP, emphasizing current clinician-relevant treatment options.

We comprehensively searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception until January 2026. The included studies evaluated any available systemic treatment for managing adult or juvenile-onset RRP. The main outcomes were complete remission, partial response, and adverse events. All the data analyses were performed using STATA 18 BE.

We included 35 studies comprising 925 patients. In juvenile-onset RRP, pooled complete remission with systemic bevacizumab was 60% (95% CI 34-87%), and pooled partial response was 46% (95% CI 21-71%). In adult-onset RRP, pooled complete remission with systemic bevacizumab was 44% (95% CI 26-62%), and pooled partial response was 61% (95% CI 43-79%). The most frequently reported bevacizumab adverse events were hypertension (40%), proteinuria (26%), and epistaxis (22%). HPV-specific immunotherapies (including FDA-approved zopapogene imadenovec-drba [Papzimeos; PRGN-2012] for adults and investigational INO-3107) and PD-1/PD-L1-directed therapies demonstrated encouraging early-phase activity but were too heterogeneous for quantitative pooling.

Systemic bevacizumab remains the most mature systemic option with consistent real-world evidence and published dosing guidance. HPV-specific immunotherapy has recently transformed adult RRP management with an FDA-approved, short-course treatment option; ongoing studies will clarify optimal sequencing with bevacizumab and the role of checkpoint inhibition.