Juvenile-onset Recurrent Respiratory Papillomatosis Research Articles

Management Challenges And Outcome Of Juvenile Onset Respiratory Papillomatosis In A Tertiary Hospital In North Central Nigeria: A Preliminary Study

Background/Aim: Juvenile Onset Recurrent Respiratory Papillomatosis (JoRRP) is a benign tumour attributed to human papillomavirus infection with a high propensity to recur despite appropriate treatment. It is relatively rare but the commonest benign tumour of the larynx in children. This study is aimed at evaluating its management challenges.
 Materials and methods: This was a retrospective review of patients with JoRRP at Ear, Nose and Throat (ENT) Department, University of Ilorin Teaching Hospital over a 7-year period. The patients' biodata, mode of presentations, surgical care, histopathological findings and management outcome were reviewed.
 Results: A total number of ten patients were diagnosed with JoRRP during the study period. Male to female ratio was 1:1. All the children were delivered per vaginal and sixty percent were first children of their mothers. Hoarseness, breathy voice and worsening difficulty in breathing were the presentation in 7 (70%) of cases, while 3 (30%) presented with only hoarseness and breathy voice. They all presented first to General Practitioners and Paediatricians before ENT Specialist assessment and six (60%) patients presented to ENT department 6 months or more after the onset of symptoms. They all had direct laryngoscopy and excisional biopsy of laryngeal papillomatous lesions. Thirty percent had tracheostomy done. There is a statistical significant relationship between tracheostomy rate and recurrence rate of JoRRP.
 Conclusion: JoRRP is a rare but potentially life-threatening benign tumor of the respiratory tract. Most of our patients presented late and were misdiagnosed at presentation. The key to good management outcome remains early diagnosis, adequate management and regular follow-up.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution's Experience.

Medical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP. A retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented. Of the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile-onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new-onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%). Systemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial-to-stable response. 4 Laryngoscope, 2024.

Pulmonary Involvement in Recurrent Respiratory Papillomatosis: A Systematic Review.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I2: 85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I2: 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

A user-centered smart inhaler algorithm for targeted drug delivery in juvenile onset recurrent respiratory papillomatosis treatment integrating computational fluid particle dynamics and machine learning

Recurrent respiratory papillomatosis (RRP) is a chronic condition primarily affecting children, known as juvenile onset RRP (JORRP), caused by a viral infection. Antiviral medications have been used to reduce the need for frequent surgeries, slow the growth of papillomata, and prevent disease spread. Effective treatment of JORRP necessitates targeted drug delivery (TDD) to ensure that inhaled aerosolized drugs reach specific sites, such as the larynx and glottis, without harming healthy tissues. Using computational fluid particle dynamics (CFPD) and machine learning (ML), this study (1) investigated how drug properties and individual factors influence TDD efficiency for JORRP treatment and (2) developed personalized inhalation therapy using an ML-empowered smart inhaler control algorithm for precise medication release. This algorithm optimizes the inhaler nozzle position and diameter based on drug and patient-specific data, enhancing drug delivery to the larynx and glottis. CFPD simulations show that particle size significantly affects deposition fractions in the upper airway, emphasizing the importance of particle size selection. Additionally, optimal nozzle diameter and delivery efficiency depend on particle size, inhalation flow rate, and release time. The ML-based TDD strategy, employing a classification and regression tree model, outperforms conventional inhalation therapy by achieving a higher delivery efficiency to the larynx and glottis. This innovative concept of an ML-empowered smart inhaler represents a promising step toward personalized and precise pulmonary healthcare through inhalation therapy. It demonstrates the potential of AI-driven smart inhalers for improving the treatment outcomes of lung diseases that require TDD at designated lung sites.

Systemic bevacizumab for treatment of recurrent respiratory papillomatosis.

To characterize treatment response of recurrent respiratory papillomatosis (RRP) including adult-onset RRP (AORRP) and juvenile-onset RRP (JORRP) to systemic bevacizumab (bev), and share our treatment regimen experience. Patients were enrolled in bev treatment based on a pathologically confirmed diagnosis of squamous papilloma. According to lesion characteristics and medical history, systemic bev was used as preoperative adjuvant therapy, postoperative adjuvant therapy, or primary therapy. The assessment of treatment response relied on the morphological changes of lesions. Vocalization and voice-related quality of life were evaluated using the voice handicap index-30 (VHI-30) for adults and the pediatric VHI (pVHI) for children. Adverse effect was monitored through patient self-reported symptoms and regular follow-ups. This study included 24 patients, comprising nine AORRP and 15 JORRP cases. In AORRP, all patients (100%) exhibited various degrees of response to systemic bev, with 5 (55.56%) achieving complete response (CR). Among JORRP patients, 14 (93.33%) showed a response to systemic bev, with 8 (53.33%) achieving CR and currently being followed up. No instances of aggravation were observed during systemic bev treatment. A total of 21 patients (21/24, 87.50%) reported voice improvement, accompanied by reduced VHI-30 or pVHI scores across all aspects, including total, functional, physical, and emotional dimensions. No grade 3 or higher adverse events occurred. The most common adverse events were grade 1 gum bleeding (n = 4, 16.67%) and grade 1 proteinuria (n = 4, 16.67%). Systemic bev can be used as a powerful therapy for both AORRP and JORRP. The findings provide a reference to the systemic bev treatment for RRP.

An unusual case of Juvenile-onset Recurrent Respiratory Papillomatosis with lower airway involvement in a 15-month-old boy

An unusual case of Juvenile-onset Recurrent Respiratory Papillomatosis with lower airway involvement in a 15-month-old boy

Use of adjuvant intravenous bevacizumab for aggressive recurrent respiratory papillomatosis- A case report

Recurrent Respiratory Papillomatosis (RRP) is a benign condition which needs frequent surgical interventions for debulking of papillomatosis lesions for securing the airway. There is no definitive treatment for the management of RRP so far. Bevacizumab either intralesional or systemic has emerged as a promising solution for RRP patients undergoing repeated surgeries. We are reporting a case of a 6-year-old child with juvenile onset RRP who was treated by surgical excision of lesion with adjuvant systemic bevacizumab therapy.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2022.

For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.

Intralesional Cidofovir: A Systematic Review of Administration Protocols and Long-term Recurrence Rates in Adult and Juvenile Recurrent Respiratory Papillomatosis

This is a systematic review aimed to explore Cidofovir administration protocols, recurrence rates, and long-term effectiveness for severe cases of recurrent respiratory papillomatosis (RRP). The primary goal was to identify current practices, determine the preferred protocol, and assess the adjuvant therapy's ability to prevent long-term papilloma recurrence in juvenile and adult-onset disease. The following databases were searched: Pubmed, Google Scholar (pages 1-10), EMBASE, Scopus, ISI (clarivate), Cochrane Library, and Journal Storage from 1996 to June 2022. Articles that reported the use of intralesional Cidofovir in RRP and reported remission/recurrence rates with follow-up were included in the review. The systematic review was registered through PROSPERO and contains the detailed protocol for the conduction of the review. A total of 389 records were identified, 126 titles and abstracts screened, 45 studies fully read, and 30 studies met the inclusion criteria. Two hundred and fourteen adult-onset RRP (AORRP) and 126 juvenile-onset RRP (JORRP) cases were treated with Cidofovir across the included studies. There was no universal protocol for administering Cidofovir, with variations in concentration, treatment period, number and interval of injections, and follow-up duration. Most lesions showed human papilloma virus types 6 and 11. Recurrence rates varied, and other outcomes reported included remission rates, lesion reduction, surgical intervals, and side effects. Some studies demonstrated significant improvements in disease severity and extended intervals between recurrences after Cidofovir administration. The analysis of 30 studies reveals the need for greater consistency in reporting treatment parameters and outcomes. The use of recurrence-free period as an outcome measure and the potential benefits of a concentration of 7.5mg/mL are identified. Additionally, the importance of viral typing within papilloma lesions is emphasized. To further enhance understanding and establish optimal protocols, future research should focus on uniform reporting, including severity, dosage, interval, treatment duration, functional outcome, and related procedures. PROSPERO CRD42022299549.

Efficacy of Systemic Bevacizumab for Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. 4 Laryngoscope, 134:577-581, 2024.

Role Of CO2 Laser & Microdebrider In The Treatment Of Juvenile Onset Recurrent Respiratory Papillomatosi.

To compare the efficacy of two main treatment modalities of microdebrider and carbon dioxide laser excision for juvenile onset recurrent respiratory papillomatosis. The retrospective study was conducted in May 2021 at the Combined Military Hospital, Kharian, Pakistan, and comprised data from July 1, 2007, to January 31, 2020, of patients of either gender aged 2-12 years who were treated for juvenile onset recurrent respiratory papillomatosis either with microdebrider excision in group A or carbon dioxide laser excision in group B. Extent and severity of disease was documented as per the Derkay-Coltrera grading system. Data was analysed using SPSS 20. Of the 39 patients, 23(59%) were girls and 16(41%) were boys. The overall mean age at the time of procedure was 6.62±2.06 years. Group A had 22(56.4%) subjects; 15(68.2%) girls and 7(31.8%) boys, while group B had 17(43.6%) cases; 8(47%) girls and 9(53%) boys. The mean operative time for group A was 40.91±11.50 minutes and for group B it was 60.59±19.51 minutes. Postoperative breathing and oedema status was better for group A (p<0.05), while there was no significant difference regarding postoperative pain, residual disease and repeat surgeries (p>0.05). Microdebrider was found to be superior to carbon dioxide laser excision in the treatment of juvenile onset recurrent respiratory papillomatosis.

[Human papillomavirus prevalence and type distribution in Chinese juvenile-onset recurrent respiratory papillomatosis patients].

Objective: To evaluate HPV prevalence and type distribution in Chinese juvenile-onset recurrent respiratory papillomatosis (JoRRP) patients. Methods: We searched China National Knowledge Infrastructure, Wanfang data, China Biology Medicine disc, PubMed, Embase, and the Cochrane Library for studies assessing HPV infection of Chinese JoRRP patients up to 1 October, 2022. Two authors independently performed literature selection, data extraction, and quality assessment. HPV prevalence and HPV type-specific prevalence were pooled using a random effects model after Freeman-Tukey double arcsine transformation. All analyses were performed with R 4.1.3 software. Results: Nineteen publications investigating HPV infection of JoRRP patients were included in the final analyses. Of these, 16 studies reported HPV prevalence with a sample size of 1 528 patients, and 11 studies reported HPV6 prevalence and HPV11 prevalence with a sample size of 611 patients. All studies were graded as medium quality. In Chinese JoRRP patients, the synthesized HPV prevalence was 92.0% (95%CI:86.0%-96.6%, I2=87%), HPV6 prevalence was 42.4% (95%CI:34.9%-50.1%, I2=61%), and HPV11 prevalence was 72.3% (95%CI:59.0%-83.9%, I2=87%). All the pooled prevalence persisted in subgroup analyses stratified by publication year, sample size, and specimen type (P>0.05). There was no evidence of publication bias. In Chinese JoRRP patients, HPV16, 18, 31, 33, 52, and 58 prevalence was very low. Conclusions: Our findings suggested high HPV prevalence in Chinese JoRRP patients, and the most common HPV types were HPV6 and HPV11.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange Augments Oxygenation in Children With Juvenile Onset Recurrent Respiratory Papillomatosis During Surgery: A Prospective Randomized Crossover Controlled Trial.

Evidence is lacking regarding the efficacy of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in tubeless anesthesia, especially in pediatric patients. This study aimed to evaluate the use of THRIVE for juvenile onset recurrent respiratory papillomatosis (JORRP) patients. Twenty-eight children aged 2 to 12 years with JORRP, abnormal airways, and ASA physical status II-III that presented for surgical treatment under general anesthesia were included in this study. Each patient received 2 interventions in random order, with a 5-minute washout period between treatments: apnea without oxygen supplementation and apnea with THRIVE intervention. The primary outcome apnea time was defined as the duration from withdrawal of intubation to reintubation and resumption of controlled ventilation. The secondary outcomes were the mean transcutaneous carbon dioxide (tcco2) increase rate, the minimum pulse oxygen saturation (Spo2) during apnea, and the occurrence of unexpected adverse effects. The median apnea time in the THRIVE period was significantly longer than that in the control period (8.9 [8.6-9.4] vs 3.8 [3.4-4.3] minutes; mean difference [95% confidence interval (CI)], 5.0 [4.4-5.6]; P < .001) for all patients. The rate of CO2 change in the control period was higher than that in the THRIVE period both for patients aged 2 to 5 years old (6.29 [5.19-7.4] vs 3.22 [2.92-3.76] mm Hg min-1; mean difference [95% CI], 3.09 [2.27-3.67]; P < .001) and for patients aged 6 to 12 years old (4.76 [3.7-6.2] vs 3.38 [2.64-4.0] mm Hg min-1; mean difference [95% CI], 1.63 [0.75-2.56]; P < .001). The minimum Spo2 was significantly higher in the THRIVE period than in the control period (mean difference [95% CI], 19.7 [14.8-22.6]; P < .001). Our findings demonstrate that THRIVE safely increased the apnea time among children with JORRP undergoing surgery and decreased the rate of carbon dioxide increase. THRIVE is clinically recommended as an airway management technique for tubeless anesthesia in apneic children.

Recurrent laryngeal papillomatosis: multimodal therapeutic strategies. Literature review and multicentre retrospective study.

Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP. A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up. Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis. Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration.

Molecular Mechanisms of Carcinogenesis in Pediatric Airways Tumors.

Primary tumors of the airways in the pediatric population are very rare entities. For this reason, little is known about the pathogenesis of these neoplasms. Understanding the biology has different practical implications: for example, it could help in the differential diagnosis, have a prognostic significance, or may lead to the development of a targeted therapy. The aim of this article is to present the current knowledge about pediatric airways tumors, focusing on the molecular mechanisms that cause the onset and progression of these neoplasms. After a brief introduction of epidemiology and clinical presentation, the tumorigenesis of the most frequent pediatric airways tumors will be described: Juvenile-onset recurrent respiratory papillomatosis (JORRP), Subglottic Hemangiona (SH), Rhabdomyosarcoma (RMS), and Mucoepidermoid carcinoma (MEC).

Laryngeal Suction tube: A Novel Technique for Tracheal Ventilation in an Obstructed Airway in a Child with Respiratory Papillomatosis.

Airway obstruction in a child requires expedite management in addition to comprehensive discussion between the Otolaryngology and Anaesthesiology team to formulate a treatment plan to ensure safe airway. Juvenile-onset recurrent respiratory papillomatosis (JORRP) is an exophytic benign laryngeal lesion which poses a great challenge when presented with respiratory distress. This paper presents a novel, safe and cost-effective approach to temporary tracheal ventilation of the obstructed airway in a child with juvenile-onset recurrent respiratory papillomatosis using the laryngeal suction tube connected to general anaesthetic (GA) machine. Rigid laryngeal suction tube is placed through the side-port of Lindholm laryngoscope and connected to breathing circuit of GA machine. Manual bagging ventilation with 100% FiO2 achieved good oxygenation throughout the debulking of the papilloma without hindering the surgical field. Our technique utilizes the readily available equipment whilst enabling safe anaesthesia and providing good surgical field during excision of obstructive papillomatous airway lesion.

Intralesional Bevacizumab as Adjuvant Therapy for Juvenile Onset Recurrent Respiratory Papillomatosis: A Systematic Review.

Background: Respiratory papillomatosis is one of the common benign lesions of the airway that is often difficult to treat and carries significant morbidity. Bevacizumab is a monoclonal antibody that acts upon vascular endothelial growth factor receptor and is known to have an effect in respiratory papillomatosis. This study aims to systematically review the literature on efficacy of intralesional Bevacizumab in juvenile onset respiratory papillomatosis. Materials and methods. A systematic search of literature in various databases was conducted. The search was restricted to the English language, however, no restrictions were made regarding the date of publication keeping December 31st, 2020 as the last date of publication. We strictly complied with the PRISMA guidelines. Results. Of 145 articles analyzed, only 3 were selected as eligible and a total of twenty-one cases were evaluated. There was improvement in anatomic Derkay score after initiating intralesional Bevacizumb with reduction in the number of surgeries. Where reported, voice related functional outcomes also were also improved. No adverse effect related to the drug was reported. Conclusion: Intralesional Bevacizumab can be a promising efficacious, and safe adjuvant in the management of JORRP. Well-designed studies are further required in the future to prove its efficacy and safety over other adjuvants available.

Systematic review of the use of human papillomavirus vaccine as adjuvant therapy for juvenile-onset recurrent respiratory papillomatosis.

Juvenile-onset RRP (JoRRP) is considered a rare disease with high morbidity and healthcare costs. The management of RRP has received much scientific attention in recent years and several treatment methodologies have been explored, including therapeutic use of HPV vaccine. There has been increasing interest in the off-label use of the vaccine in virus-induced disease processes such as RRP, due to its immunomodulatory effect and activating role on the innate and adaptive immune system. This review explores the efficacy of the HPV vaccination as a therapeutic tool in the pediatric population. The review of the English literature included three electronic databases, PubMed, SCOPUS, and Cochrane, without publication date restrictions. Studies and reports identified by the database search were reviewed and assessed by two independent reviewers. The literature searches identified 768 unique citations, from which 204 duplicates were removed (n=564). A total of 547 articles were excluded as they did not meet our inclusion criteria. A total of 12 studies (3 experimental studies, 3 case series, 6 case reports) that met the inclusion criteria and reported one or more of the outcomes of interest were included for our review. The assessment of the outcome measures evaluated (number of surgeries during the follow-up period, ISI, SPM, Derkay or severity scores, and remission status) revealed that eight out of 12 studies included in the review showed varying degrees of potential benefits from the administration of the vaccine as a treatment modality compared to surgical interventions and/or concurrent adjuvant therapies alone. We conclude that while the therapeutic use of HPV vaccination has shown promise for some JoRRP patients, it overall remains uncertain with the currently available data. There is a need for a prospective multi-centric trial with a larger sample size to fully characterize the potential use of the vaccine in the management of JoRRP.

Recurrent Respiratory Papillomatosis: Quality of Life Data from an International Patient Registry.

Quality of life studies in recurrent respiratory papillomatosis (RRP) have traditionally relied upon clinician-designed survey instruments. This study's objective is to report quality of life outcomes from a patient-designed questionnaire. Patients who provided health information and completed a quality of life questionnaire were identified from the RRPF-CoRDS patient registry. Demographic, clinical, and quality of life measures were collected. Means and standard deviationswere calculated for continuous data, and frequencies and percentages were calculated for categorical data. Outcomes for patients with juvenile-onset RRP (JORRP) and adult-onset RRP (AORRP) were compared using Student's t-tests for continuous data and χ2 analyses for categorical data. Seventy-three patients with RRP were identified (JORRP: 32; AORRP: 41). Common clinical symptoms included raspy voice (78.1%) and dyspnea (61.6%). The majority (97.3%) of patients reported feeling debilitated by their diagnosis, and 94.5% of patients reported avoiding participation in career and/or social activities due to their voice quality. Due to their RRP, 65.7% reported missing at least five work days each month. Social anxiety was reported in 79.5% of patients, though only 28.8% of the cohort reported utilizing mental health services. The median (range) lifetime number of surgeries received was 20 (1 - 3). Most patients (57.5%) reported paying at least 5% of their annual income towards RRP-related medical care. RRP presents high mental and fiscal burden. Our results highlight data from a quality of life questionnaire designed by RRP patients, and may help to elucidate potential disconnects between what clinicians and RRP patients consider most impactful. 4 Laryngoscope, 2022.

Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients.

Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3+ T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFβ in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.