HPV Genotype as a Predictor of Bevacizumab Treatment Response in Recurrent Respiratory Papillomatosis Patients

Objective: : This study aimed to evaluate the clinical efficacy and safety of systemic bevacizumab in recurrent respiratory papillomatosis (RRP) and to explore the potential predictive value of human papillomavirus (HPV) genotype in this condition.Methods: : A total of 34 patients with confirmed HPV6- or HPV11-associated RRP who received at least three doses of systemic bevacizumab were enrolled. Disease burden and clinical response were evaluated based on the number of interventions, Derkay scores, and voice-related quality of life (assessed using the Voice Handicap Index-30 for adults or the pediatric Voice Handicap Index for children) before and after treatment. Adverse events were documented and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Additionally, vascular endothelial growth factor A (VEGFA) expression in RRP tissues was measured by immunohistochemistry.Results: : The overall response rate (ORR) was 70.59%. The frequency of surgical interventions was significantly reduced following treatment (median reduction from 2 to 0; P < 0.0001), and Derkay scores also showed a significant reduction (median reduction from 7.0 to 1.5; P < 0.0001). Adverse events were observed in 38.24% of patients, all of which were grade 1-2 and manageable. In juvenile-onset recurrent respiratory papillomatosis (JORRP), patients infected with HPV11 exhibited an ORR of 76.92%, with 57.58% achieving a ≥ 50% reduction in Derkay scores. In contrast, among patients infected with HPV6, the ORR was 57.14%, and only 45.83% demonstrated a ≥ 50% improvement in Derkay scores. Although these differences did not reach statistical significance, HPV11-positive patients with JORRP appeared to have a more favorable prognosis. Conversely, in adult-onset RRP (AORRP), patients with HPV11 infection had an ORR of 40% and a 16.67% rate of ≥ 50% Derkay score reduction, while those infected with HPV6 demonstrated an ORR of 88.89% and a 77.78% rate of significant Derkay score improvement. Similarly, a statistically significant reduction in surgical frequency before and after treatment was observed only in HPV11-positive JORRP patients and HPV6-positive AORRP patients. All groups of RRP showed VEGFA expression, but there was no significant difference.Conclusion: : Systemic bevacizumab is effective and well-tolerated in both JORRP and AORRP. HPV genotype may influence therapeutic response and clinical outcomes in RRP patients receiving bevacizumab treatment. Specifically, HPV11-positive JORRP patients and HPV6-positive AORRP patients appear to derive greater benefit.