(724) Risk Factors Associated with Dysplastic/Malignant Transformation in HPV-Related Recurrent Respiratory Papillomatosis: A Systematic Review

Introduction: Recurrent respiratory papillomatosis (RRP) is a benign HPV-related condition that typically involves the larynx. Although most cases remain benign, some patients develop dysplasia or, more rarely, malignant transformation. This study reviews the available literature to better understand which clinical and viral factors may increase this risk.

Methods: This systematic review and meta analysis was conducted in accordance with PRISMA guidelines. A comprehensive literature search of PubMed, Embase, and Web of Science identified 2,966 records published between 1945 and November 2025 evaluating HPV related recurrent respiratory papillomatosis with outcomes of dysplasia or malignant transformation. Included studies involved adult and pediatric human subjects. No interventions were assigned, as the study synthesized observational data from the published literature. Outcomes included histopathologically confirmed dysplasia and malignancy, and evaluated variables included demographic factors, clinical characteristics, disease severity, HPV subtype, tobacco exposure, disease duration, and treatment related factors when available.

Results: Older age was the most consistent factor associated with dysplastic or malignant change. When pooled, adult cohorts showed a mean age difference of 6.78 years (95% CI: 0.68–12.88; p = 0.03) between patients with benign disease and those with dysplasia or carcinoma. In the qualitative synthesis, multiple studies reported a higher rate of transformation in patients with HPV-11. Smoking showed a non-significant trend toward increased risk (OR: 1.74; 95% CI: 0.88–3.47; p = 0.11). No clear associations were found for cidofovir, immunosuppression, or diabetes.

Conclusions: Increasing age appears to be the most reliable predictor of dysplasia or malignant transformation in RRP, with possible added risk from HPV-11. Future randomized studies using standardized criteria may help clarify the relative contributions of patient factors, disease characteristics, and treatment-related variables to pathologic progression and inform surveillance strategies.