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

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.

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.

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.

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.