Immunologic Response and Clinical Course After Off-label Nonavalent HPV Vaccination in Juvenile-onset Recurrent Respiratory Papillomatosis Patients

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BACKGROUND: Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a rare airway disease caused by human papillomavirus (HPV), most commonly HPV6 or HPV11. Affected children often require repeated surgical procedures, and no curative therapy exists. Off-label HPV vaccination has been proposed as an adjunctive treatment, but vaccine-induced immune responses and the relevance of circulating HPV DNA in benign disease remain unclear. METHODS: We longitudinally evaluated 2 children with JoRRP who received off-label nonavalent HPV vaccination between 2020 and 2025. Serum HPV-specific binding and neutralizing antibodies were measured before vaccination and after the second and third doses using multiplex serology and a pseudovirion-based neutralization assay. During bronchoscopic follow-up, bronchoalveolar lavage fluid and available biopsy samples were analyzed for HPV DNA. In 1 patient, plasma was additionally tested for circulating HPV DNA by digital polymerase chain reaction. RESULTS: Both children had low or undetectable HPV-specific antibodies at baseline. Vaccination induced strong binding and neutralizing antibody responses against vaccine-included HPV types. During post-vaccination follow-up of 12-29 months after completion of the vaccination series, HPV DNA became undetectable in bronchoalveolar lavage samples, and no new papilloma growth was observed after the last post-vaccination intervention. Circulating HPV DNA was not detected at any time point in the patient tested. CONCLUSIONS: Nonavalent HPV vaccination induced robust neutralizing antibody responses in children with JoRRP and was temporally associated with clinical stabilization. Larger studies are needed to clarify clinical benefit and biomarker utility.

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