RARE DISEASE
Recurrent respiratory papillomatosis
Recurrent respiratory papillomatosis
Recurrent respiratory papillomatosis
Drug discovery
11
drugs
With orphan designations
Overview
Recurrent respiratory papillomatosis (RRP) is a rare, HPV-driven disorder (predominantly types 6/11) characterized by recurrent benign papillomas in the upper aerodigestive tract. These lesions cause progressive airway obstruction, dysphonia, and respiratory compromise. The disease follows a chronic, unpredictable course requiring repeated surgical interventions. While histologically benign, 10–55% of cases show dysplasia, with rare malignant transformation risk [1][4][7].
Burden
Morbidity: Patients endure 4–6 annual surgeries (20% require >10), with lifetime tracheostomy risk and vocal dysfunction [1][4][16].
Economic: Initial 2-year costs reach $76,000/patient; total U.S. annual burden exceeds $123M [2][9][16].
Psychosocial: Chronic interventions disrupt education/employment and increase anxiety, particularly with pulmonary spread (9% of cases) [4][12][16].
Therapies
Surgical: Laser/microdebrider resection for airway preservation; office-based KTP/PDL laser use reduces general anesthesia needs [3][5][8].
Adjuvant therapies: Intralesional/systemic bevacizumab, cidofovir, or interferon-alfa for refractory cases [2][3][8][12].
Emerging options: HPV vaccination (Gardasil-9) shows therapeutic benefit in reducing recurrence; INO-3107 vaccine received FDA Breakthrough Therapy designation [1][2][8].
Categories: rare otorhinolaryngological diseases, rare respiratory diseases
Research Papers
748 drug discovery papers about Recurrent respiratory papillomatosis, with 4 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
748 drug discovery papers about Recurrent respiratory papillomatosis, with 4 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Updated Practice Patterns for Adjuvant Treatment of Recurrent Laryngeal Papillomatosis.
Adjuvant medical treatments are used to reduce recurrence rates of recurrent respiratory papillomatosis (RRP). Prior consensus statements on initiation of adjuvants may not reflect current practices, particularly given safety data published in the interval. The objective of this study is to distribute information on current practices in management of RRP, including the use of adjuvant medications, use of surgical modalities and other treatments, monitoring, as well as attitudes and philosophies. Survey study. Email-distributed survey. A survey was distributed to a large group of laryngologists and pediatric otolaryngologists and responses were collected and analyzed. Responses were collected from 86 surgeons, including 71 specific to adult patients and 16 specific to pediatric patients. Laryngologists reported a threshold of 2 surgeries per year to initiate intralesional adjuvant treatments, while pediatric otolaryngologists reported thresholds of 4 surgeries per year for intralesional bevacizumab and 5 surgeries per year for cidofovir. Variable responses between groups were reported for other factors leading to initiation of adjuvants, surgical tools used, practices around HPV vaccination and testing, monitoring, and attitudes and philosophies regarding treatment of RRP. Current practice patterns and attitudes reflect increased comfort with the initiation of adjuvant treatments earlier in the disease course. New medical treatments that promise a shift away from primarily surgical treatment are highly anticipated.
2026-07-28 | Combined Analysis of scRNA-seq and Bulk RNA-seq Sequencing Revealing the Heterogeneity of Recurrent Respiratory Papillomatosis and Key Molecular Mechanisms of Its Occurrence and Development.
Recurrent respiratory papillomatosis (RRP) is a benign tumor that is highly prone to recurrence and has the potential to become malignant, caused by human papillomavirus (HPV) infection. The underlying mechanism is unclear, and new targets need to be explored urgently. This study integrated single-cell and bulk RNA-seq data, screened key genes through cell communication, machine learning, and animal models, constructed a predictive model, and completed drug prediction and independent validation. This single-cell sequencing study revealed an active fibroblast-epithelial dialogue within the RRP, and defined three subtypes of fibroblasts and their developmental trajectories. It identified key genes such as GJB2 and the ceRNA regulatory network, revealed imbalances in the immune microenvironment, and predicted potential therapeutic drugs. The key genes identified in this study, GJB2, IL36G, and S100A7, can serve as potential molecular markers and therapeutic targets for the early diagnosis, prognosis assessment, and precise treatment of RRP.
2026-07-20 | Long-term predictors of recurrence in pediatric recurrent respiratory papillomatosis.
To identify predictors of recurrence in pediatric recurrent respiratory papillomatosis (RRP) using a 10-year prospective cohort, evaluating traditional factors (HPV type, lesion characteristics) and novel patient- and disease-specific variables, and their association with Speech-Quality-of-Life (SQOL). We conducted a multicenter, prospective cohort study of 740 patients (629 pediatric, 111 adult) with histologically confirmed RRP from 2014 to 2023 at five high-volume ENT centers in Pakistan. The primary cohort comprised pediatric patients (onset < 18 years); while adult-onset cases were analyzed as a secondary comparative cohort to evaluate pediatric onset as an independent predictor of recurrence. Data included demographics, HPV type (6, 11, 16, 18), lesion number/location, surgery type, adjuvant therapy, tracheostomy history, age at onset, prior surgery intervals, lesion growth rate, socioeconomic status (SES), comorbidities, and immunodeficiency. The primary outcome was time to first recurrence requiring surgical intervention. Patients without recurrence were censored at their last follow-up visit. Time-to-event outcomes were analyzed using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression adjusting for all covariates. Standardized lesion assessment demonstrated high inter-rater reliability (kappa = 0.78). Recurrence occurred in 65.0% of pediatric patients versus 45.9% of adult-onset patients (p < 0.001)Independent predictors included pediatric onset, HPV types 11, 16, 18, multiple lesions, tracheal involvement, younger age at onset, faster lesion growth, low SES, immunodeficiency, and shorter prior surgery intervals. Adjuvant therapies were associated with reduced recurrence (Cidofovir HR 0.62; Interferon HR 0.66; Bevacizumab HR 0.53). Surgery type did not independently predict recurrence. Median follow-up was 6.8 years. Lower SQOL scores correlated with higher recurrence frequency (Pearson r = - 0.52, p < 0.001). Recurrence in pediatric RRP is multifactorial. Novel predictors-lesion growth rate, SES, and immunodeficiency-enhance risk stratification. Adjuvant therapies show associative benefit, and SQOL correlates with recurrence, highlighting the clinical importance of functional outcomes.
2026-07-14 | A Comprehensive Overview of Physical and Adjuvant Therapies for Recurrent Respiratory Papillomatosis: Current Evidence and Future Directions.
This article aims to provide a comprehensive overview of the management strategies for recurrent respiratory papillomatosis (RRP), focusing on the evolution from traditional surgical approaches to contemporary precision medicine, and evaluating the efficacy and safety of current physical therapeutic modalities and adjuvant treatments, thereby offering a framework for clinical decision-making. A comprehensive overview. PubMed, Scopus and Web of Science. We conducted a systematic literature search across three databases from 1995 to 2026. Used the following key words: recurrent respiratory papillomatosis(RRP), physical therapeutic modalities, human papillomavirus (HPV), and adjuvant therapies. Data pertaining to study design, participant characteristics, treatment modalities, and outcomes-such as recurrence rate, surgical interval, vocal function, and adverse events-were systematically extracted. Given the clinical and methodological diversity among the studies, a narrative synthesis was adopted to summarize the evidence. Additionally, the quality of evidence was evaluated using the GRADE approach. Of 128 screened abstracts, 95 full-text articles were reviewed. Current evidence demonstrates that various physical therapeutic modalities-such as the precision of carbon dioxide(CO2) laser, the epithelial-sparing potassium titanyl phosphate (KTP) laser, the rapid debulking coblation, and the cryotherapy-effectively manage RRP. Adjuvant drug therapies, including cidofovir, bevacizumab, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, and DNA immunotherapy prolong surgical intervals, while therapeutic HPV vaccination is associated with reduced surgical frequency. The management of recurrent respiratory papillomatosis (RRP) has evolved into a patient-centered, multimodal strategy that prioritizes airway patency, voice preservation, and quality of life. Treatment is personalized based on lesion characteristics, integrating physical therapeutic modalities with targeted adjuvant medical therapies. Future research focuses on therapeutic vaccines and biomarker discovery to advance toward a cure.
2026-07-09 | Zopapogene imadenovec-drba, a novel adenovector-based immunotherapy, induces complete and durable responses in recurrent respiratory papillomatosis
Robustefficacy was observedfollowing zopa treatment with 51% (34 to 69; 95% CI) of patients achieving a complete response (CR), defined as no requirement for interventions in the 12m following treatment.Here we present data up to 51m of followup. ResultsAs of December 15, 2025, with a median duration of follow-up of 36m (range: 30-51m), 83% (15/18) of patients who achieved a CR at 12m remainin CR with no recurrence of papilloma requiring surgicalor medical intervention.Out of the 15 patientsremaining in CR, 3 patients have reached 4 years of follow-up.No new safety events were observed during long-term follow-up. ConclusionsZopa treatment demonstrated significant clinicalbenefit with the vast majorityof CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety.Updatedfollow-up results for all patientsachieving CR will be available at the time of presentation.
2026-08-17 | Updated Practice Patterns for Adjuvant Treatment of Recurrent Laryngeal Papillomatosis.
Adjuvant medical treatments are used to reduce recurrence rates of recurrent respiratory papillomatosis (RRP). Prior consensus statements on initiation of adjuvants may not reflect current practices, particularly given safety data published in the interval. The objective of this study is to distribute information on current practices in management of RRP, including the use of adjuvant medications, use of surgical modalities and other treatments, monitoring, as well as attitudes and philosophies. Survey study. Email-distributed survey. A survey was distributed to a large group of laryngologists and pediatric otolaryngologists and responses were collected and analyzed. Responses were collected from 86 surgeons, including 71 specific to adult patients and 16 specific to pediatric patients. Laryngologists reported a threshold of 2 surgeries per year to initiate intralesional adjuvant treatments, while pediatric otolaryngologists reported thresholds of 4 surgeries per year for intralesional bevacizumab and 5 surgeries per year for cidofovir. Variable responses between groups were reported for other factors leading to initiation of adjuvants, surgical tools used, practices around HPV vaccination and testing, monitoring, and attitudes and philosophies regarding treatment of RRP. Current practice patterns and attitudes reflect increased comfort with the initiation of adjuvant treatments earlier in the disease course. New medical treatments that promise a shift away from primarily surgical treatment are highly anticipated.
2026-07-28 | Combined Analysis of scRNA-seq and Bulk RNA-seq Sequencing Revealing the Heterogeneity of Recurrent Respiratory Papillomatosis and Key Molecular Mechanisms of Its Occurrence and Development.
Recurrent respiratory papillomatosis (RRP) is a benign tumor that is highly prone to recurrence and has the potential to become malignant, caused by human papillomavirus (HPV) infection. The underlying mechanism is unclear, and new targets need to be explored urgently. This study integrated single-cell and bulk RNA-seq data, screened key genes through cell communication, machine learning, and animal models, constructed a predictive model, and completed drug prediction and independent validation. This single-cell sequencing study revealed an active fibroblast-epithelial dialogue within the RRP, and defined three subtypes of fibroblasts and their developmental trajectories. It identified key genes such as GJB2 and the ceRNA regulatory network, revealed imbalances in the immune microenvironment, and predicted potential therapeutic drugs. The key genes identified in this study, GJB2, IL36G, and S100A7, can serve as potential molecular markers and therapeutic targets for the early diagnosis, prognosis assessment, and precise treatment of RRP.
2026-07-20 | Long-term predictors of recurrence in pediatric recurrent respiratory papillomatosis.
To identify predictors of recurrence in pediatric recurrent respiratory papillomatosis (RRP) using a 10-year prospective cohort, evaluating traditional factors (HPV type, lesion characteristics) and novel patient- and disease-specific variables, and their association with Speech-Quality-of-Life (SQOL). We conducted a multicenter, prospective cohort study of 740 patients (629 pediatric, 111 adult) with histologically confirmed RRP from 2014 to 2023 at five high-volume ENT centers in Pakistan. The primary cohort comprised pediatric patients (onset < 18 years); while adult-onset cases were analyzed as a secondary comparative cohort to evaluate pediatric onset as an independent predictor of recurrence. Data included demographics, HPV type (6, 11, 16, 18), lesion number/location, surgery type, adjuvant therapy, tracheostomy history, age at onset, prior surgery intervals, lesion growth rate, socioeconomic status (SES), comorbidities, and immunodeficiency. The primary outcome was time to first recurrence requiring surgical intervention. Patients without recurrence were censored at their last follow-up visit. Time-to-event outcomes were analyzed using Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression adjusting for all covariates. Standardized lesion assessment demonstrated high inter-rater reliability (kappa = 0.78). Recurrence occurred in 65.0% of pediatric patients versus 45.9% of adult-onset patients (p < 0.001)Independent predictors included pediatric onset, HPV types 11, 16, 18, multiple lesions, tracheal involvement, younger age at onset, faster lesion growth, low SES, immunodeficiency, and shorter prior surgery intervals. Adjuvant therapies were associated with reduced recurrence (Cidofovir HR 0.62; Interferon HR 0.66; Bevacizumab HR 0.53). Surgery type did not independently predict recurrence. Median follow-up was 6.8 years. Lower SQOL scores correlated with higher recurrence frequency (Pearson r = - 0.52, p < 0.001). Recurrence in pediatric RRP is multifactorial. Novel predictors-lesion growth rate, SES, and immunodeficiency-enhance risk stratification. Adjuvant therapies show associative benefit, and SQOL correlates with recurrence, highlighting the clinical importance of functional outcomes.
2026-07-14 | A Comprehensive Overview of Physical and Adjuvant Therapies for Recurrent Respiratory Papillomatosis: Current Evidence and Future Directions.
This article aims to provide a comprehensive overview of the management strategies for recurrent respiratory papillomatosis (RRP), focusing on the evolution from traditional surgical approaches to contemporary precision medicine, and evaluating the efficacy and safety of current physical therapeutic modalities and adjuvant treatments, thereby offering a framework for clinical decision-making. A comprehensive overview. PubMed, Scopus and Web of Science. We conducted a systematic literature search across three databases from 1995 to 2026. Used the following key words: recurrent respiratory papillomatosis(RRP), physical therapeutic modalities, human papillomavirus (HPV), and adjuvant therapies. Data pertaining to study design, participant characteristics, treatment modalities, and outcomes-such as recurrence rate, surgical interval, vocal function, and adverse events-were systematically extracted. Given the clinical and methodological diversity among the studies, a narrative synthesis was adopted to summarize the evidence. Additionally, the quality of evidence was evaluated using the GRADE approach. Of 128 screened abstracts, 95 full-text articles were reviewed. Current evidence demonstrates that various physical therapeutic modalities-such as the precision of carbon dioxide(CO2) laser, the epithelial-sparing potassium titanyl phosphate (KTP) laser, the rapid debulking coblation, and the cryotherapy-effectively manage RRP. Adjuvant drug therapies, including cidofovir, bevacizumab, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, and DNA immunotherapy prolong surgical intervals, while therapeutic HPV vaccination is associated with reduced surgical frequency. The management of recurrent respiratory papillomatosis (RRP) has evolved into a patient-centered, multimodal strategy that prioritizes airway patency, voice preservation, and quality of life. Treatment is personalized based on lesion characteristics, integrating physical therapeutic modalities with targeted adjuvant medical therapies. Future research focuses on therapeutic vaccines and biomarker discovery to advance toward a cure.
2026-07-09 | Zopapogene imadenovec-drba, a novel adenovector-based immunotherapy, induces complete and durable responses in recurrent respiratory papillomatosis
Robustefficacy was observedfollowing zopa treatment with 51% (34 to 69; 95% CI) of patients achieving a complete response (CR), defined as no requirement for interventions in the 12m following treatment.Here we present data up to 51m of followup. ResultsAs of December 15, 2025, with a median duration of follow-up of 36m (range: 30-51m), 83% (15/18) of patients who achieved a CR at 12m remainin CR with no recurrence of papilloma requiring surgicalor medical intervention.Out of the 15 patientsremaining in CR, 3 patients have reached 4 years of follow-up.No new safety events were observed during long-term follow-up. ConclusionsZopa treatment demonstrated significant clinicalbenefit with the vast majorityof CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety.Updatedfollow-up results for all patientsachieving CR will be available at the time of presentation.
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Drug Discovery Landscape
11 orphan drug designations for Recurrent respiratory papillomatosis, including 1 approved therapy.
11 orphan drug designations for Recurrent respiratory papillomatosis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
a single recombinant plasmid-derived DNA-based therapeutic vaccine specifically targeting the E6 and E7 antigens of both HPV 6 and HPV 11 | vaccines | FDA | 2026-01-15 | — | Advaccine Biopharmaceuticals Suzhou Co., Ltd. |
pembrolizumab | antibodies | FDA | 2025-01-03 | — | Massachusetts General Hospital |
bevacizumab | antibodies | FDA | 2024-07-02 | — | DELBERT SAS |
Gorilla adenovirus vector expressing HPV6 and HPV11 antigens | gene therapies | EMA | 2024-01-12 | — | FGK Representative Service GmbH |
Doruxapapogene ralaplasmid | gene therapies | EMA | 2023-05-22 | — | PHARA |
zopapogene imadenovec-drba [Papzimeos] | gene therapies | FDA | 2021-03-17 | 2025-08-14 | Precigen, Inc. |
A recombinant plasmid-derived DNA-based vaccine targeting the E6 and E7 antigens of both HPV6 and HPV11 | oligonucleotides | FDA | 2020-07-28 | — | Inovio Pharmaceuticals, Inc. |
modified vitamin D binding protein | proteins | FDA | 2017-04-17 | — | Efranat, Ltd. |
Recombinant fusion protein of Mycobacterium bovis BCG Hsp65 and HPV16 E7 | proteins | FDA | 2001-03-19 | — | StressGen Biotechnologies, Inc. is now Nventa |
Interferon alfa-2b (recombinant) | proteins | FDA | 1988-08-17 | — | Schering Corporation |
Interferon alfa-nl | proteins | FDA | 1987-10-16 | — | Glaxo Wellcome Inc. |
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