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Recurrent respiratory papillomatosis (RRP) is a rare and chronic disease characterized by papillomatous growths in the airway. Low-risk types of human papillomavirus (HPV), specifically HPV6 and HPV11, are associated with the pathogenesis of RRP. Laryngotracheal papillomas can cause dysphonia and airway obstruction, and pulmonary papillomas can cause post-obstructive pneumonias and death. There is no cure for RRP and no approved pharmacologic therapies. Current standard of care is surgical therapy or laser ablation to remove the lesions and preserve the normal structure of the larynx. Individuals often require dozens to hundreds of procedures during their lifetime. However, these therapies do not address the chronic HPV infection. There are an estimated 27,000 cases in the US and 1,000 new cases annually, but data on incidence is limited.

There are no guidelines for the management and treatment of RRP. However, several organizations have issued consensus statements and position papers. The Department of Otolaryngology – Head and Neck Surgery published a consensus statement (2024) on the administration of systemic bevacizumab (Avastin®, biosimilars [intravenous infusion]) as a nonsurgical treatment option for individuals with RRP. The statement recommends systemic Avastin as a first-line therapy and advises evaluating all individuals for treatment eligibility to minimize or eliminate the need for surgery. Treatment is expected to be indefinite. The document adopts a neutral stance on Avastin biosimilars, neither endorsing nor discouraging their use.

The American Academy of Otolaryngology issued a position statement (2021) on Gardasil®-(Human Papillomavirus 9-valent vaccine intramuscular injection [recombinant]) vaccination. The statement encourages the use of Gardasil-9 HPV vaccination in all individuals 9 to 45 years of age, highlighting a potential benefit for both the prevention and treatment of RRP since the vaccine covers subtypes most commonly implicated in RRP, as well as other conditions. This recommendation has also been endorsed by both the National Institute on Deafness and Other Communication Disorders and Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The American Laryngological, Rhinological, and Otological Society published a consensus statement on pulmonary RRP (2025), in which 33 recommendation statements were made for screening, diagnosis, management, and treatment. Regarding therapy, the statement emphasizes systemic Avastin as a commonly used option and encourages consideration of clinical trials exploring other systemic treatments.

Papzimeos is a non-replicating adenoviral vector-based immunotherapy designed to express a fusion antigen of selected regions of human papillomavirus (HPV) proteins expressed in HPV 6- and HPV 11-infected cells. Papzimeos is designed to generate an immune response directed against HPV 6 and HPV 11 proteins in individuals with recurrent respiratory papillomatosis. 

Papzimeos was evaluated in an open-label, single-arm study in 38 adults with recurrent respiratory papillomatosis (RRP). Individuals received Papzimeos on days 1, 15, 43, and 85. The primary efficacy endpoint was the percentage of individuals with a complete response to Papzimeos treatment, defined as no requirement of surgical intervention in the 12 months after treatment. In the 35 individuals that received a dose of 5 × 10¹¹ particle units (PU) per injection, the median age at RRP diagnosis was 35 years (range 1-68) and median age at the start of treatment was 49 years (range 20-88). 23 (66%) individuals were diagnosed with adult-onset RRP and 12 (34%) with juvenile-onset disease. Most individuals were male [20 (57%) of 35] and required up to hundreds of lifetime clinically indicated interventions to control RRP [median 40 (range 3 to > 400)]. Four (11%) of 35 individuals had pulmonary RRP evaluable by RECIST criteria. The median number of previous medical treatments for RRP was 2 (range 1-8). The median number of clinically indicated interventions in the 12 months before the study treatment was 4 (3-10). The median pretreatment anatomic Derkay score was 8 (3-31). The median pretreatment VHI-10 score was 24 (6-40), indicating severe dysphonia. At the dose of 5 × 10¹¹ PU per injection, 18 of 35 individuals received a complete response at 12 months [complete response rate 51% (95% CI: 34, 69)]. At the dose of 1× 10¹¹ PU per injection, no individual (0 of 3) received a complete response. Warnings and precautions for Papzimeos include injection site reactions and thrombotic events. The most common adverse reactions (≥ 5%) with Papzimeos use were injection site reactions, fatigue, chills, pyrexia, myalgia, and nausea.