Cases Of Recurrent Respiratory Papillomatosis Research Articles

Human papilloma virus (HPV) vaccination is associated with reduced number of surgical treatments, an observational study on recurrent respiratory papillomatosis in Northern Sweden

Background Recurrent respiratory papillomatosis (RRP) is a wart-like lesion mainly affecting the larynx, caused by human papillomavirus (HPV) genotypes 6 and 11. The disease affects both children and adults, and there is no cure. Surgery is the current symptom-relieving treatment; however, HPV vaccination is used as an adjuvant treatment. Aims and Objectives The aims were to study effects of HPV vaccination in RRP cases and to compare juvenile-onset to adult-onset disease and high treatment frequency (TF) to low TF cases. Material and Methods Medical records of RRP patients were studied from May 2006 to January 2023. Eighty-five RRP cases, tested for HPV genotypes with PapilloCheck®, were included. Vaccination- onset- and treatment analysis were performed. Results Twelve percent of the cases were vaccinated. The number of surgeries decreased from 2.0 to 0.8/year after HPV vaccination. Most cases had an adult-onset and less than one treatment per year. Juvenile-onset cases had a higher vaccination treatment ratio compared to adult-onset. Conclusions HPV vaccination was associated with a lower number of treatments per year, supporting the use of vaccination as an adjuvant treatment. Significance Vaccination as adjuvant treatment to surgery may lead to increased quality of life for RRP patients and saved healthcare resources.

Public health impact and cost-effectiveness of switching from bivalent to nonavalent vaccine for human papillomavirus in Norway: incorporating the full health impact of all HPV-related diseases

AimThe objective of this study was to estimate and compare the cost-effectiveness of switching from a bivalent to a nonavalent human papillomavirus (HPV) vaccination program in Norway, incorporating all nonavalent vaccine-preventable HPV-related diseases and in the context of the latest cervical cancer screening program.MethodsA well-established dynamic transmission model of the natural history of HPV infection and disease was adapted to the Norwegian population. We determined the number of cases of HPV-related diseases and subsequent number of deaths, and the economic burden of HPV-related disease under the current standard of care conditions of bivalent and nonavalent vaccinations of girls and boys aged 12 years.ResultsCompared to bivalent vaccination, nonavalent vaccination averted an additional 4,357 cases of HPV-related cancers, 421,925 cases of genital warts, and 543 cases of recurrent respiratory papillomatosis (RRP) over a 100-year time horizon. Nonavalent vaccination also averted an additional 1,044 deaths over the 100-year time horizon when compared with bivalent vaccination. Total costs were higher for the nonavalent strategy (10.5 billion NOK [€1.03 billion] vs. 9.3–9.4 billion NOK [€915–925 million] for bivalent vaccination). A switch to nonavalent vaccination had a higher vaccination cost (4.4 billion NOK [€433 million] vs. 2.7 billion NOK [€266 million] for bivalent vaccination) but resulted in a savings of 627–694 million NOK [€62–68 million] in treatment costs. A switch to nonavalent vaccination demonstrated an incremental cost-effectiveness ratio of 102,500 NOK (€10,086) per QALY versus bivalent vaccination.ConclusionsUsing a model that incorporated the full range of HPV-related diseases, and the latest cervical cancer screening practices, we found that switching from bivalent to nonavalent vaccination would be considered cost-effective in Norway.

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.

Abstract 4121: Durable stable disease with nivolumab, PD-1 inhibitor, and subsequent bevacizumab, Anti-VEGF monoclonal antibody, in long standing recurrent respiratory papillomatosis with lung squamous cell carcinoma

Abstract Background: Recurrent respiratory papillomatosis (RRP) is a human papilloma virus (HPV) associated benign disease, which, in rare cases, can develop into lung squamous cell carcinoma. Treatment options are limited with no approved systemic adjuvant therapy and the disease requires frequent surgical resection to prevent airway obstruction. Therefore, expanding available treatment options remains a highly important, but unmet need in RRP. Herein, we present a case of RRP with squamous cell carcinoma of lung that demonstrated durable stable disease with nivolumab and subsequent bevacizumab. Case presentation: A 48-year-old woman with long standing RRP since teenager, who underwent multiple microsuspension laryngoscopies, debridements including laryngeal lesions, and ultimately, 5 years ago, video assisted thoracic surgery (VATS) resection of right upper lobe mass, confirming squamous cell carcinoma, has been managed with debulking surgery on tracheal lesions by ENT on regular basis. Nivolumab, a programmed death-1 blockade, 3 mg/kg every 2 weeks was started given squamous cell carcinoma of lung. Stable disease (SD) in lung lesions was achieved on nivolumab for one year but she required more frequent debulking of tracheal lesions. After multidisciplinary discussion with Otorhinolaryngology, she was started on bevacizumab, vascular endothelial growth factor inhibitor, 10 mg/kg every 6 weeks. Follow-up CT scans in 10 weeks showed a decrease in size of a left lower lobe mass to 27 mm from 32 mm in the previous image. After one year, administration of bevacizumab was spaced out to every 12 weeks. She requires less debulking surgery and the last debulking surgery was approximately 3 years ago. She maintains SD for over 4 years since starting bevacizumab. Discussion: Our patient with RRP and squamous cell carcinoma of lung demonstrated SD on nivolumab before she was switched to bevacizumab. In addition, her SD on bevacizumab of more than 4 years with 12 weeks of maintenance interval is encouraging as there is no current standard of care treatment for RRP. Despite difficulty in running clinical trials in RRP due to its rareness, additional studies evaluating the efficacy of PD-1 inhibitor or anti-VEGF monoclonal antibody on RRP are warranted. Citation Format: Horyun Choi, Jinah Kim, Yeun Ho Lee, Leeseul Kim, Young Kwang Chae. Durable stable disease with nivolumab, PD-1 inhibitor, and subsequent bevacizumab, Anti-VEGF monoclonal antibody, in long standing recurrent respiratory papillomatosis with lung squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4121.

Systemic Bevacizumab Treatment for Recurrent Respiratory Papillomatosis: Long-Term Follow-Up.

Systemic bevacizumab is a new adjuvant therapy for recurrent respiratory papillomatosis (RRP) that has shown promising preliminary results in children. The objective of this study was to report the largest series to date that includes long-term follow-up data on bevacizumab treatment. Retrospective chart review. Retrospective review of seven pediatric patients treated within the past 6 years with systemic bevacizumab for RRP refractory to traditional debridement. All seven patients had a significant reduction in disease burden after initiation of systemic bevacizumab. There have been no major complications associated with systemic therapy so far. Median duration of bevacizumab treatment was 2.13 years. Three of the seven patients have been on treatment for over 3 years with the longest duration of treatment in our first patient now at 5.5 years. One patient experienced significant disease recurrence on two occasions when therapy was temporarily discontinued and was recently diagnosed with squamous cell carcinoma of the lung. Systemic bevacizumab is an effective therapy for cases of severe RRP with promising results both in short-term and long-term follow-up. Side effects are minimal. Patients must be followed closely to determine appropriate dosing intervals to control disease and to screen for disease progression. 4 Laryngoscope, 132:2071-2075, 2022.

A classical case of recurrent respiratory papillomatosis in an adult

A 22-year-old female university student presented with hoarseness of voice for a few months. She had difficulty to project her voice and underwent initial voice assessment and stroboscopy, which mild–moderate dysphonia characterised by breathy husky quality with mild roughness on Grade of hoarseness; Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale. She did not complain on any difficulties swallowing or breathing. She has a background of mild Asthma for which she uses inhalers but otherwise is generally well in herself. She is a non-smoker and is fully vaccinated.

P8‐148: A case of recurrent respiratory papillomatosis with malignant transformation in a young Filipino female presenting as multiple pulmonary nodules

P8‐148: A case of recurrent respiratory papillomatosis with malignant transformation in a young Filipino female presenting as multiple pulmonary nodules

Recurrent respiratory papillomatosis: clinical characteristics and viral genotyping in a Brazilian population.

ABSTRACTThis study presents 25 cases of recurrent respiratory papillomatosis (RRP) that occurred in Sao Luis, Maranhao State, Northeast region, Brazil, between January 2007 and December 2018. Sociodemographic and clinical profile of patients as well as human papillomavirus (HPV) infection status were evaluated. Clinical and histopathological data were collected from the patients’ medical records. For the HPV infection analysis, DNA was extracted and subjected to amplification by a nested polymerase chain reaction. Viral genotyping was performed by automated sequencing. The median age of patients was 12.40 ± 12.6. years, and the juvenile form of the disease (68%) was the predominant form of disease. Female participants were predominant (60%), and they were from cities located in the interior of the State (60%). The most common clinical manifestation was dysphonia; recurrence was observed in most cases (56%), and tracheostomy was necessary in seven patients (26.9%). When comparing the RRP forms, patients in the juvenile-RRP group had higher recurrence rates and need of tracheostomy than those in the adult-RRP group. The viral genotyping analysis revealed that 47.8% of patients had low-risk HPVs, whereas 13.1% had high-risk HPVs, and in 39.1% of patients the viral genotype was not obtained. HPV-6 was the most prevalent type and Juvenile-RRP was more prevalent in our population. HPV was present at a high rate, and HPV-6 was the predominant genotype. This study serves as the basis for further studies to be conducted in the Brazilian population. Our findings aid the better understanding of RRP, possibly suggesting some prognostic factors associated with the disease aggressiveness.

Cost of treating recurrent respiratory papillomavirus in commercially insured and medicaid patients

The study objective was to estimate the first 2 years' direct costs of treating new cases of juvenile-onset and adult-onset recurrent respiratory papillomatosis (RRP) and determine the predictors of treatment costs. Cases were patients diagnosed with RRP in commercial insurance claims in 2011-2014 and Texas Medicaid in 2008-2012 for treatment of RRP. Controls were patients without a diagnosis of HPV-related cancer or RRP, matched with cases by age, sex, geographic area, date of diagnosis of RRP, and propensity score. Total health care costs in the first 2 years after diagnosis were obtained from cases and matched controls. A generalized linear model was created to identify predictors of monthly costs. In commercially insured patients, a total of 122 cases of juvenile-onset (<18 years old) and 1824 cases of adult-onset (≥18 years old) RRP were identified. The mean first 2 years' cost difference between cases and controls was $58,733 for juvenile-onset disease and $11,185 for adult-onset disease after model adjustments. In the Texas Medicaid population, 73 cases of juvenile-onset and 96 cases of adult-onset RRP were identified. The mean first 2 years' cost difference between cases and controls was $76,115 for juvenile-onset disease and $4,633 for adult-onset disease after model adjustments. The first 2 years' medical costs difference of juvenile-onset and adult-onset RRP among commercially insured and Medicaid population were approximately $60,000 to $70,000 and $5,000 to $11,000, respectively, and should be considered in HPV vaccination promotion investment decisions. N/A Laryngoscope, 130:1186-1194, 2020.

A Method for Reconstruction of Anterior Commissure Glottal Webs With Endoscopic Fibro-Mucosal Flaps.

Anterior-commissure (AC) cicatrization and web formation is a difficult problem that can result from a variety of clinical scenarios. An advancement-rotation flap utilizing papillomatous epithelium and subepithelial fibrous tissue has been previously described. For patients in whom there was not excessive redundant papillomatosis covering the AC web, including other clinical scenarios, a microlaryngoscopic procedure was designed to lengthen the glottal/subglottal aperture using substantial local fibro-mucosal tissue. Although it has been done for over a decade, this approach is not widely known and to our knowledge not photo-documented. Retrospective. An analysis was done with Institutional Review Board approval that identified 42 patients who underwent 53 procedures to treat AC webs, which were reconstructed with local soft-tissue flaps and without any device/stent to maintain the glottal aperture. The microlaryngoscopic method and technical nuances for this approach with and without diseased epithelium are described and photo-documented. Tactical mucosal incisions were made to facilitate advancement and/or rotation of fibro-mucosal flaps with enough length to resurface the medial aspect of 1 vocal fold. The scarred submucosal soft tissue in the AC region was separated with cold instruments, and the flaps were sutured in position. Variations of this method are demonstrated mobilizing fibro-mucosal soft tissue from different locations, including the web itself, contralateral vocal fold, infrapetiole region, and/or the inner aspect of the thyroid lamina below the anterior-commissure tendon. Of the 53 cases in which anterior commissure glottal webs were reconstructed with endoscopic fibro-mucosal flaps, 31 of 53 had recurrent respiratory papillomatosis (RRP). Redundant RRP comprised the majority of the flap in 14 of 31 RRP cases. Fibro-mucosal tissue without a substantial amount of disease occurred in 17 of 31 RRP cases. Of the remaining 22 AC web cases, the primary diagnoses observed were: glottic cancer = 7 of 22, intraepithelial dysplasia = 10 of 22, glottic trauma = 3 of 22, congenital = 1 of 22, and radiotherapy = 1 of 22. Endolaryngeal utilization of local fibro-mucosal tissue to lengthen the glottal/subglottal aperture for AC webs is an effective strategy. It can be done without using devices or keels for webs that are congenital or from nonsurgical trauma, idiopathic disease, or postsurgical traumatic cicatrization of the anterior commissure subsequent to treatment of epithelial disease (eg, cancer, dysplasia, and RRP). Normalizing the architecture of the anterior commissure was a valuable asset in patients who require future treatment of epithelial diseases, especially in an office-based setting.

The PD-1 and PD-L1 pathway in recurrent respiratory papillomatosis.

Generation of an immunosuppressive microenvironment may enable a persistent human papillomavirus infection in the setting of an otherwise normal immune system. We hypothesized that expression of the T-lymphocyte co-inhibitory receptor programmed death 1 (PD-1) and its ligand PD-L1 would be increased in the recurrent respiratory papillomatosis (RRP) microenvironment compared to normal controls. Case-control study. Formalin-fixed paraffin-embedded respiratory papilloma and normal controls were obtained under institutional review board approval, stained for CD4, CD8, FoxP3, and PD-1, and scored by automated cell count. PD-L1 staining was scored by a blinded pathologist using an adjusted inflammation score that accounted for epithelial and immune infiltrate. Thirty-nine RRP cases and seven controls were studied. All immunologic markers demonstrated significantly increased staining in RRP specimens compared to normal controls (all P < .01). PD-1 correlated with both CD4 (P < .0001) and CD8 (P < .001) cell counts. Epithelial staining for PD-L1 (68%) and PD-L1+ infiltrating immune cells (76%) were observed in the majority of papilloma samples. The strongest staining for PD-L1 was usually observed in the basal papilloma layer adjacent to the immunologic infiltrate in the vascular core. Disease severity inversely correlated with CD8 cell counts (P = .01). A correlation between disease severity and other immunologic markers was not observed. Most RRP specimens demonstrate PD-1 T-lymphocyte infiltration and PD-L1 expression on both papilloma and infiltrating immune cells. This study suggests that this checkpoint pathway may be contributing to local immunosuppression in RRP, and opens the door for clinical trials utilizing PD-blocking monoclonal antibodies. NA Laryngoscope, 128:E27-E32, 2018.

Juvenile recurrent respiratory papillomatosis: 10-year audit and Australian prevalence estimates.

To estimate the prevalence of juvenile onset recurrent respiratory papillomatosis (RRP) in Australia, describe its epidemiological profile, and assess the positive predictive value of International Classification of Disease, 10th revision (ICD-10) code D14.1 (benign neoplasm of larynx) in children for hospitalization due to RRP. Retrospective case series. Retrospective case review undertaken at the three tertiary pediatric hospitals in New South Wales (Australia's largest state), by reviewing medical records of patients aged 0 to 16 years admitted during 2000-2009 containing the ICD-10 Australian modification code D14.1 or other possible disease (D14.2-4, D14.3, D14.4) and RRP-related procedure codes. For RRP diagnoses, we recorded treatment dates, length of stay, extent of disease, and surgical and adjuvant treatments. The positive predictive value (PPV) of code D14.1 and median number of hospitalizations per year were applied to national hospital separations data from 2000/2001 to 2012/2013 to estimate disease prevalence. We identified 30 cases of RRP using code D14.1, which had a PPV of 98.1%, with no further cases identified using other codes. Fifty-seven percent of cases were female, median age of onset was 36 months, and median treatment duration was 36 months (mean = 40 months, range = 1-118). There was one patient death. Between 2000 and 2013, the estimated national prevalence rate was 0.81 per 100,000 aged < 15 years, peaking at age 5 to 9 years (1.1 per 100,000). RRP prevalence can be monitored after human papillomavirus vaccination programs using routine hospital data. 4 Laryngoscope, 126:2827-2832, 2016.

Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis

A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.

Abstract CN03-02: Conditionally reprogrammed cells for personalized medicine.

Abstract CN03-02: Conditionally reprogrammed cells for personalized medicine.

Clinical characteristics and HPV type in recurrent respiratory papillomatosis in Colombia

Describe factors associated with aggressive forms of recurrent respiratory papillomatosis (RRP). One hundred eighty-nine RRP cases diagnosed between 1985 and 2009 were identified in pathological records. HPV was detected by the SPF-10 method with broad spectrum primers, (version 1). 113 patients had only one surgery (less aggressive) and 76, two or more interventions (more aggressive). The likelihood of aggressive lesions decreased with increasing age at diagnosis and HPV-11 was associated with no significant increase in the risk of aggressiveness. The age at diagnosis was the main determinant of RRP aggressiveness.

Juvenile respiratory papillomatosis: Risk factors for severity

Juvenile recurrent respiratory papillomatosis is caused mainly by human papillomavirus genotypes 6 or 11, acquired at birth or during pregnancy from an infected mother. Recurrent respiratory papillomatosis is characterized by recurring warts growing most commonly in the larynx. Multiple surgical procedures and the risk of airway obstruction contribute to the devastating impact of this disease. Some children will go into remission after a few surgeries whereas others will require repeated interventions over several years. Further understanding of the risk factors associated with severity may contribute to tailored treatments. A retrospective study of cases diagnosed between January 1995 and December 2008 was conducted to study determinants of severe forms of juvenile recurrent respiratory papillomatosis. Demographic and clinical variables were abstracted from children's medical charts and mothers' delivery charts. Viral factors (HPV genotyping and viral load) were studied from archived biopsies. Specific HLA class II alleles and killer-cell immunoglobulin-like receptors genes were tested from saliva samples. Logistic regression was performed to identify risk factors for severity. Overall, 31 pediatric cases of recurrent respiratory papillomatosis were identified. The only significant factor associated with severe forms of recurrent respiratory papillomatosis was the maternal history of condylomas during pregnancy (OR: 12.05 [P=0.05]). The analysis failed to identify risk factors that could be used clinically to identify recurrent respiratory papillomatosis cases likely to take a severe course. Although too early to determine, vaccination against the HPV types involved most commonly in recurrent respiratory papillomatosis may provide the best hope to prevent severe forms of this disease.

Estimating the prevalence of and treatment patterns for juvenile onset recurrent respiratory papillomatosis in Australia pre-vaccination: a pilot study

Recurrent respiratory papillomatosis (RRP) causes serious morbidity. RRP in Australia may be eliminated in the near future following the implementation of a national vaccination program using a human papillomavirus (HPV) vaccine that protects against infection with HPV types 6 and 11, those responsible for RRP. Baseline data on RRP prevalence and disease burden in Australia are lacking. Three study methods were used to estimate the burden of juvenile onset RRP in Australia. We conducted a retrospective chart review of RRP cases treated at The Children's Hospital at Westmead over 10 years, examined the coding of these cases, and then calculated and applied the positive predictive value of the codes to national data to estimate the prevalence of RRP in Australia. We also conducted an online survey of otolaryngologists in Australia who manage RRP. Nineteen patients were treated at the hospital over 10 years, involving 359 admissions. We estimate that between 33 and 56 RRP cases aged <20 are being treated nationally per year (0.6-1.1 per 100 000 persons), with children 5-9 years having a higher estimated rate of 1.2-1.8 per 100 000. Among 39 otolaryngologists treating juvenile onset RRP, the majority (73%) treated RRP in a paediatric tertiary hospital, and used the microdebrider for ablation of lesions. Our estimates of RRP disease burden agree with international estimates. As a small number of clinicians treat RRP nationally, we believe that establishment of a national RRP register is both feasible and necessary to monitor the impact of vaccination.

Recurrent Respiratory Papillomatosis Arising in Trachea not Affecting Larynx

Recurrent respiratory papillomatosis (RRP) is an infrequent benign neoplasm commonly involving the upper respiratory tract with laryngeal predilection. The diagnosis and treatment of this disease are challenging due to its nonspecific clinical presentations and recurrent nature. We report here a rare juvenile case of RRP arising in the trachea without laryngeal lesions. Our experiences indicate that a high awareness of RRP and proper consideration in the right clinical context are prerequisites for early diagnosis, and a combination of multiple treatment modalities should be considered as a feasible treatment regimen.

Ex Vivo Analyses of Ano-genital Wart Lymphocytes to Study the Human Papillomavirus Immune Response

Human papillomavirus (HPV) is the causative agent of certain benign and malignant tumours. HPV subtypes 6 and 11 cause approximately 90% of cases of genital warts (the most common sexually transmitted disease) (1, 2) and virtually all cases of recurrent respiratory papillomatosis (3, 4). They are classified as low-risk for carcinogenesis, whilst the high-risk subtypes, such as 16 and 18, cause approximately 70% of cases of cervical cancer worldwide (5, 6). There has been intense public interest recently in the HPV prophylactic vaccines for the prevention of cervical cancer (7, 8). Since HPV infection is primarily a peripheral in-fection (and not a systemic one), the study of the im-mune response at the site of infection is a necessity in understanding and designing better therapies. We have examined the feasibility of studying the lymphocytes infiltrating ano-genital warts as a model for studying HPV infection and associated immune responses in the periphery.MATerIAl AND MeTHoDS