Juvenile-onset Recurrent Respiratory Papillomatosis Research Articles

Characterization of HPV6/11-reactive T-cell subsets in papillomas of patients with juvenile-onset recurrent respiratory papillomatosis and identification of HPV11 E7-specific candidate TCR clonotypes.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is caused by persistent infection of epithelial cells by low-risk human papillomavirus (HPV) types 6 and 11. While multiple infiltrated immune cells have been reported to mediate disease progress, knowledge of HPV-reactive T-cell subsets in papillomas remains elusive. Through single-cell RNA sequencing and RNA microarray, we found that CD8+ tissue-resident memory T (CD8+ TRM) cells with strong interferon-gamma (IFN-γ) production expanded, and were negatively correlated to the disease severity in the frequency of surgery. These IFN-γ+ CD8+ memory T cells were readily activated and expanded in vitro by autologous dendritic cells loaded with HPV11 E7 peptide pool. Moreover, T cell receptor (TCR) clonal expansion was observed in JORRP papilloma tissues, indicating a biased TCR repertoire toward HPV-specific recognition. Finally, we identified and characterized HPV11 E7-specific candidate TCR clonotypes from IFN-γ+ CD8+ memory T cells, suggesting their potential application in TCR-engineered T cells (TCR-T) therapy for HPV11-related diseases. Our findings provided insights into the specific local immune response to HPV6/11 infection and highlighted the importance of IFN-γ+ CD8+ TRM cells in anti-HPV6/11 T-cell immunity.IMPORTANCEThe persistent recurrence of human papillomavirus (HPV) 6/11 infection in papillomas underscores the failure of local immune responses in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). Our previous study demonstrated that T cells constitute the predominant immune cell population in JORRP papilloma tissues. Understanding the T-cell-mediated immune responses within JORRP papilloma tissues is crucial for disease control. In the present study, we characterized CD8+ tissue-resident memory T (CD8+ TRM) cells as the primary T-cell subset responsible for local anti-HPV6/11 immunity. Moreover, we identified two HPV11 E7-specific candidate T cell receptor (TCR) clonotypes out of IFN-γ+ CD8+ memory T cells. Overall, our findings provided insights into the local immune responses to HPV6/11 infection and offered information for developing more effective immunotherapeutic strategies against JORRP.

Recurrent Respiratory Papillomatosis in the Post–Human Papillomavirus Vaccination Era

This cross-sectional study examines the incidence of juvenile-onset recurrent respiratory papillomatosis and HPV vaccination rates from 2007 to 2022 in the US.

Chinese guideline for the diagnosis and treatment of juvenile-onset recurrent respiratory papillomatosis (2024)

Chinese guideline for the diagnosis and treatment of juvenile-onset recurrent respiratory papillomatosis (2024)

Global trends and hotspots on recurrent respiratory papillomatosis: A 20-year bibliometric analysis.

Recurrent respiratory papillomatosis (RRP) is the most common benign laryngeal tumor in children. It can cause serious psychological and mental burden on patients since RRP requires repeated surgical treatment. This study aims to delineate the global trends and identify hotspots related to RRP over the past two decades. We systematically gathered research findings on RRP from 2004 to 2023, utilizing the Web of Science as our data source. Subsequently, we performed a comprehensive bibliometric analysis of the literature using Vosviewer, CiteSpace, and Bibliometrics online analysis platform. A total of 839 publications were finally identified on RRP from 2004 to 2023. The United States has the largest number of publications (392), accounting for 46.7%. The Capital Medical University is the most productive organization (24), followed by the Centers for Disease Control and Prevention (18). The most productive journal was the Laryngoscope, with 86 publicatios. Comparatively, Vaccine is the most cited journal (2297). Craig S. Derkay ranked highest among all authors in publication (16). Burst detection shows onset, adjuvant therapy, management, juvenile-onset RRP, systemic bevacizumab, avastin, human papillomavirus vaccine are recent keywords of great interest to researchers. Research on RRP has progressed significantly over the past two decades, especially in terms of therapeutic strategies. We strongly believe that this article will provide new research directions for other researchers and may contribute to future breakthroughs in the field.

Gardasil® as adjunctive therapy for respiratory papillomatosis at Red Cross Children’s Hospital, Cape Town

Background: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is an incurable condition caused by human papilloma virus (HPV) types 6 and 11, often requiring repeated surgeries and in severe cases, tracheostomy. This imposes a significant socioeconomic burden on patients and families. Gardasil®, a proven prophylactic HPV vaccine, is emerging as a potential adjuvant therapy. We studied its response on JoRRP patients at our center.Methods: We conducted a retrospective review at Red Cross War Memorial Children’s Hospital from January 2015 to June 2022 on histologically confirmed JoRRP cases. Age at diagnosis, baseline and post-dosing Derkay-Coltrera (DC) scores (disease severity measure), inter-surgical intervals and tracheostomy, were collected.Results: Twenty-five of 30 confirmed cases were included. Average age at diagnosis was 60 months (about 5 years old), with HPV Type 6 in 40% and Type 11 in 48% of patients. All patients received at least one Gardasil® dose, 84% received a second dose and 64% a third dose. Total population DC score decreased from an average of 17 (range: 4-34) pre-first dose to 8 (range: 0-16) after three doses, indicating a 50% reduction. Surgical intervals modestly increased. More significant improvements were seen in patients with aggressive forms of the disease.Conclusion: This is the first study in Southern Africa highlighting Gardasil® as adjuvant therapy. Despite our limited sample size, new cases observed a linear reduction in DC scores and tracheostomy rates.Contribution: This suggests that Gardasil® as adjuvant therapy has the potential to reduce disease severity and extend surgical intervals.

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

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, 134:3253-3259, 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.

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.

The incidence of juvenile onset recurrent respiratory papillomatosis at Starship Children's Hospital before and after a national HPV vaccination programme: a retrospective review.

To review and compare the incidence of juvenile onset recurrent respiratory papillomatosis (JRRP) at Starship Children's Hospital (SSH) before and after the introduction of a national HPV vaccination programme. Patients treated for JRRP at SSH were identified retrospectively using ICD-10 code D14.1 over a 14-year period. The incidence of JRRP in the 10-year period prior to the introduction of HPV vaccination (1 September 1998 to 31 August 2008) was compared with the incidence after its introduction. A second comparison was made between the pre-vaccination incidence with the incidence over the most recent 6 years when the vaccination became more widely available. All New Zealand hospital ORL departments that referred children with JRRP to SSH exclusively were included. SSH manages about half of the New Zealand paediatric population with JRRP. The incidence of JRRP before the introduction of the HPV vaccination programme was 0.21 per 100,000 per year in children 14 years of age and younger. This remained stable between 2008 and 2022 (0.23 vs 0.21 per 100,000 per year). The mean incidence in the later post-vaccination period was 0.15 per 100,000 per year based on small numbers. The mean incidence of JRRP before and after the introduction of HPV has remained unchanged in children treated at SSH. More recently, a reduction in incidence has been noted, although this is based on small numbers. The low HPV vaccination rate (≤70%) may explain why a significant reduction in the incidence of JRRP seen overseas has not been observed in New Zealand. Ongoing surveillance and a national study would provide more insight into the true incidence and evolving trends.

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.