Transcriptomic Landscape of Gene Expression Profiles and Pathways in Juvenile-Onset Recurrent Respiratory Papillomatosis Tumor Tissues and Human Papillomavirus 6 and 11 E6- and E7-Overexpressing Head and Neck Squamous Cell Carcinoma Cell Lines.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is the most common benign laryngeal neoplasm in children and is considered to be primarily caused by human papillomavirus (HPV) types 6 and 11. In the present study, we performed RNA sequencing (RNA-seq) of 8 tumors and 4 adjacent nontumor tissues to explore the transcriptional profiles of JORRP tumors. A total of 1,151 upregulated genes involved in the interleukin-17 (IL-17) signaling pathway and 1,620 downregulated genes involved in dysregulated inflammatory responses were reported. Immunohistochemistry (IHC) assays confirmed the upregulation of IL-17C in JORRP tumors compared with paired adjacent nontumor tissues. Real-time PCR (RT-PCR) assays showed positive correlations between CXCL1 (CXC chemokine ligands 1) and CXCL8 and the Derkay Clinic Score of JORRP patients. We further overexpressed the HPV6 or HPV11 E6 and E7 oncogenes in SNU-1076 head and neck squamous cell carcinoma (HNSCC) cell lines and carried out RNA-seq. We found that HPV6-E6-E7 gene overexpression resulted in only 16 upregulated genes and 1 downregulated gene; however, HPV11-E6-E7 gene overexpression resulted in 1,776 upregulated genes and 461 downregulated genes compared with the control cell lines. The differentially expressed genes (DEGs) of HPV11-E6-E7 gene overexpression were positively enriched in the DNA replication-related terms by Gene Ontology (GO) analysis and the IL-17 signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Taken together, our present findings revealed IL-17 signaling pathway-related gene profiles that might contribute to disease pathogenesis and that the HPV11 E6 and E7 oncogenes promote disease progression by enhancing tumor growth and activating the IL-17 signaling pathway in JORRP patients. IMPORTANCE Juvenile-onset recurrent respiratory papillomatosis (JORRP) is primarily caused by human papillomavirus 6 (HPV6) and HPV11 infection; however, the gene signatures of tumors are currently less understood. In the present study, we performed RNA sequencing and found upregulated genes associated with the IL-17 signaling pathway and downregulated genes associated with inflammatory-related pathways. Further RNA sequencing was performed in HPV6-E6-E7- or HPV11-E6-E7-overexpressing SNU-1076 HNSCC cells lines to explore the potential pathogenic molecular mechanisms of HPV virus. We found that HPV11-E6-E7 overexpression resulted in gene expression related to DNA replication and the IL-17 signaling pathway. Our results suggested enriched that the IL-17 signaling pathway resulting from HPV11 infection might contribute to JORRP pathogenesis.

High recurrence rate in patients with juvenile-onset respiratory papillomatosis and its risk factors.

PURPOSE: To identify the recurrence rate and risk factors for recurrence in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). METHODS: A retrospective review was performed for all JORRP patients who underwent surgery between 2002 and 2019 at our institution. The demographic characteristics and clinical parameters were recorded. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze the rate of recurrence and its risk factors. RESULTS: Our study included 721 patients. The cumulative recurrence rates at 1, 5, and 10 postoperative years following initial surgery were 74.2%, 90.0%, and 94.3%, respectively. Age at diagnosis younger than 4.5 years (HR = 2.380, 95% CI [1.169-4.846], P = 0.017), high Derkay anatomical score (HR = 1.136, 95% CI [1.043-1.236], P = 0.003) and HPV type 11 infection (HR = 2.947, 95% CI [1.326-6.551], P = 0.008) were independent risk factors for recurrence. Adjuvant therapy with interferon was less likely to recur (HR = 0.237, 95% CI [0.091-0.616], P = 0.003). Additionally, gender, tracheotomy, mode of delivery, parity, expression of Ki-67, HPV vaccination, and surgical treatment method were not independently associated with recurrence (P > 0.05). CONCLUSION: Age at diagnosis younger than 4.5 years, high Derkay anatomical score and HPV type 11 infection were associated with an increased risk for recurrence in patients with JORRP. Adjuvant therapy with interferon may reduce the risk of recurrence.

Nucleotide and phylogenetic analysis of human papillomavirus type 11 isolated from juvenile-onset recurrent respiratory papillomatosis in China.

To assess the association between sequence variants of human papillomavirus (HPV) 11 and recurrent respiratory papillomatosis and the taxonomy and evolutionary history of HPV 11. Complete HPV 11 nucleotide sequences were sequenced by Illumina HiSeq2000 Analyzers and compared with the HPV 11 prototype isolate (GenBank accession number: M14119) using Blast 2.0 server software. Eighteen full-length HPV 11 genomic sequences were amplified and sequenced. A total of 49 nucleotide mutations were identified, 12 of which resulted in amino acid changes. HPV 11 variants were highly conserved; the maximum pairwise difference was approximately 0.49%. The maximum pairwise difference of the 18 variants in our research was 0.39%. HPV 11 is less polymorphic than the majority of studied HPV genotypes.

Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy.

Background: Benign migratory glossitis or geographic tongue is a chronic recurring inflammatory condition of the oral cavity. With its ephemeral characteristics, there has been reported literature showing its association with the administration of certain drugs including angiogenesis inhibitors. The antiangiogenic drugs act by selectively inhibiting the vascular endothelial growth factor (VEGF) signaling. It has been widely used as an adjunct and a maintenance agent for the treatment of various cancers. Aims: This study aims to report probable characteristic oral mucosal changes in a patient with juvenile-onset recurrent respiratory papillomatosis (JORRP) under maintenance therapy with an antiangiogenesis drug. Case description: The patient was presented with a burning sensation on having spicy food. This occurred after the completion of three cycles of bevacizumab infusion. It was associated with the appearance of migratory lesions over the tongue and evolved periods of remission and exacerbation. Clinical examination revealed lesions characteristic of the geographic tongue on the anterior two-thirds of the dorsal surface as well as the lateral surface of the tongue classified as type 2, according to Hume criteria. Oral examination revealed dental caries in relation to 52, 54, 62, 63, 74, and 85 teeth and grossly decayed 64. Topical lignocaine gel was instituted for symptomatic relief of the lesion. Full mouth rehabilitation with preventive and restorative therapeutic interventions was carried out. Clinical significance and conclusion: The documented literature along with this report put forth a probable association of geographic tongue with the use of bevacizumab drugs which requires further detailed studies. These lesions generally require symptomatic treatment with assurance only. The etiology is poorly understood. How to cite this article: Kalra N, Tyagi R, Khatri A, et al. Angiogenesis Inhibitor Drug-induced Benign Migratory Glossitis in a Patient of Juvenile-onset Recurrent Respiratory Papillomatosis under Maintenance Therapy. Int J Clin Pediatr Dent 2024;17(1):92-96.

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

Background: 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. Objective: 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. Result and Conclusion: 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.

The duration of tracheostomy dependence in patients with juvenile-onset recurrent respiratory papillomatosis.

BACKGROUND: Tracheostomy is a vital therapy for juvenile-onset recurrent respiratory papillomatosis (JORRP) to maintain an adequate airway in an emergency, yet the relationship between cannulation duration and prognosis has not been extensively explored. OBJECTIVES: To investigate the predictive influence of the duration of tracheostomy dependence on JORRP remission. MATERIALS AND METHODS: A retrospective review of JORRP patients (n = 77) with tracheostomy treated in Beijing Tongren Hospital was performed. RESULTS: The rate of decannulation was 72.7%. After decannulation for one year, the percentage of distal spread fell from 42.9 to 30.4%. Twenty-six of 77 patients (33.8%) had remission of their disease, 40 (51.9%) continued to have active disease while 11 (14.3%) died during follow-up. The cannulation duration was positively correlated with the overall duration of this disease (r = 0.6). The cut-off point of 34.9 months for cannulation duration indicated the highest predictive value of remission. Duration of cannulation >34.9 months (OR = 0.33) and distal spread (OR = 0.29) decreased odds of remission. CONCLUSION: The study demonstrates that the time span before decannulation indicates the severity of disease and cannulation aggravates the distal spread. Patients with cannulation duration ≤ 34.9 months after tracheostomy are prone to possess a relatively pleasant prognosis.

Tracheotomy as a predictor of remission and demise for juvenile-onset recurrent respiratory papillomatosis.

BACKGROUD: The pros and cons of tracheotomy, as a classic treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP), have gradually been recognized, but the exact impact of tracheotomy on remission and demise is not clear. OBJECTIVES: To investigate the predicting influence of tracheotomy on prognosis for JORRP. MATERIAL AND METHODS: Three hundred forty two patients with JORRP treated in Beijing Tongren Hospital were retrospectively reviewed. The clinical characteristics and prognosis parameters were compared in the group of tracheotomy and non-tracheotomy. RESULTS: The rate of tracheotomy was 24.6% (84/342). Among these patients, 68 (81.0%) developed the tracheal papillomatosis. The onset age of RRP occurred earlier in tracheostomized group, and patients performed tracheotomy needed a greater number of surgeries and developed distal spread more easily (p < .05). The remission rate was significantly lower (35.1 vs. 53.7%) and the mortality higher (13.1 vs. 1.2%) in patients with tracheotomy than non-tracheotomy. Tracheotomy decreased odds of remission (OR = 0.48; 95%CI: 0.28-0.83) and increased odds of demise (OR = 11.98; 95%CI: 3.21-44.65). CONCLUSIONS: The age at diagnosis, the surgical frequency and the medical level of hospital are important factors affecting the occurrence of tracheotomy. Patients who had undergone tracheotomy are prone to possess the low remission rate and high mortality.

Factors Related to Extralaryngeal Spread in Juvenile Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: To identify factors associated to increased risk of extra-laryngeal spread in pediatric patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart review. METHODS: A retrospective study was conducted evaluating the clinical charts of patients younger than 16 years with histopathologically confirmed RRP treated between January 2014 and December 2018. Characteristics of patients with and without extra-laryngeal disease dissemination were compared. Odds ratios were calculated and multivariate logistic regression analysis was performed. RESULTS: Data from 82 patients were analyzed. Mean age at symptom onset was 42 months. Fifteen (18.29%) patients had extra-laryngeal spread (ELS) at time of diagnosis and in four, the disease continued to spread to other sites. Of 67 patients with disease restricted to the larynx, 17 (25.37%) developed ELS during the disease course. Human papilloma virus (HPV) typing was performed in 49 (59.8%) patients; in 28 (57.1%) HPV subtype 6 was identified and in 21 (42.9%) HPV subtype 11. ELS was found in 11 patients with serotype 11 (52.38%) and in seven patients with serotype 6 (25%) (P = .048). Statistically significant differences for ELS were also found for age at diagnosis younger than 5 years (P = .045), presence of tracheostomy (P = .031), and need for adjuvant therapy (P = .010). CONCLUSIONS: Age at diagnosis of RRP younger than 5 years and presence of tracheostomy were factors related to ELS. A statistically significant association between infection with HPV subtype 11 and ELS were also observed. Adjuvant medication might be considered a protective factor against ELS. Laryngoscope, 131:1652-1656, 2021.

HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening.

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

Distribution Characteristics of Juvenile-Onset Recurrent Respiratory Papillomatosis at First-Time Surgery.

OBJECTIVES: The lesion distribution of juvenile-onset recurrent respiratory papillomatosis (JORRP) during first-time surgery has been rarely reported. The purpose of this study was to describe the anatomical distribution of papilloma across 25 Derkay sites during initial surgery and to assess the impact of the lesion distribution on disease severity. METHODS: Surgical videos and medical records of 106 patients with JORRP (27 aggressive and 79 nonaggressive cases) were retrospectively reviewed. Lesion locations were recorded using Derkay anatomical sites. Logistic regression was used to analyze the effect of the lesion distribution on disease severity. RESULTS: Among the 106 patients, the true vocal cords (90.6% left, 84.0% right) were the most frequently involved site, followed by the false vocal cords (39.6% left, 35.8% right) and the anterior commissure (26.4%). Two patients (1.9%) had tracheal involvement. Patients with false vocal cord involvement (odds ratio [OR] = 3.425, 95% confidence interval [CI] [1.285, 9.132], P = .014) and a younger age at diagnosis (OR = .698, 95% CI [.539, .905], P = .007) were more likely to require more than 4 procedures in the year following first-time surgery. CONCLUSIONS: Lesions were most common on the true vocal cords. False vocal cord involvement and a younger age at diagnosis were risk factors for disease severity.

Systemic Bevacizumab (Avastin) for Juvenile-Onset Recurrent Respiratory Papillomatosis: A Systematic Review.

OBJECTIVES: Juvenile onset recurrent respiratory papillomatosis (JORRP) can cause severe or disseminated disease. Surgical treatment may be inadequate. Systemic bevacizumab has shown initial success for severe JORRP. The objective of this systematic review was to assess usage, effectiveness, and safety of this treatment. METHODS: We searched PubMed, Embase, and Web of Science for studies of humans with JORRP treated with systemic bevacizumab. Two researchers independently reviewed the studies to determine inclusion and aggregate data on patient characteristics, dosing protocols, treatment response, adverse events, and level of evidence. RESULTS: Of 80 identified articles, 12 studies were included detailing 20 distinct cases. At a mean age of 12.8 years (range = 1-43 years) patients received initial dosing of 5 to 10 mg/kg of bevacizumab followed by ongoing doses at a mean 3-week intervals (range = 2-5 weeks). All patients had clinically significant disease reduction with reduced need for surgery. Six patients (30%) had complete response in at least one involved anatomic site. Eleven (55%) required no surgery after initiating treatment. There was recurrence in all four patients whose treatment was stopped, but had rapid improvement with treatment resumption. Six (30%) experienced mild or moderate adverse events. CONCLUSIONS: Marked improvement in severe JORRP has been reported from systemic bevacizumab. Treatment protocols vary, and treatment discontinuation was not feasible in any reported patient. Based on currently available data, systemic bevacizumab can be considered for severe JORRP as it appears to be well tolerated and effective. A clinical trial could enhance the understanding of its safety and efficacy for this indication. Laryngoscope, 131:1138-1146, 2021.

Histological Severity Risk Factors Identification in Juvenile-Onset Recurrent Respiratory Papillomatosis: How Immunohistochemistry and AI Algorithms Can Help?

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a condition characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. The course of the disease remains unpredictable: some children experience minor symptoms, while others require multiple interventions due to florid growth. Our study aimed to identify histologic severity risk factors in patients with JoRRP. Forty-eight children from two French pediatric centers were included retrospectively. Criteria for a severe disease were: annual rate of surgical endoscopy ≥ 5, spread to the lung, carcinomatous transformation or death. We conducted a multi-stage study with image analysis. First, with Hematoxylin and eosin (HE) digital slides of papilloma, we searched for morphological patterns associated with a severe JoRRP using a deep-learning algorithm. Then, immunohistochemistry with antibody against p53 and p63 was performed on sections of FFPE samples of laryngeal papilloma obtained between 2008 and 2018. Immunostainings were quantified according to the staining intensity through two automated workflows: one using machine learning, the other using deep learning. Twenty-four patients had severe disease. For the HE analysis, no significative results were obtained with cross-validation. For immunostaining with anti-p63 antibody, we found similar results between the two image analysis methods. Using machine learning, we found 23.98% of stained nuclei for medium intensity for mild JoRRP vs. 36.1% for severe JoRRP (p = 0.041); and for medium and strong intensity together, 24.14% for mild JoRRP vs. 36.9% for severe JoRRP (p = 0.048). Using deep learning, we found 58.32% for mild JoRRP vs. 67.45% for severe JoRRP (p = 0.045) for medium and strong intensity together. Regarding p53, we did not find any significant difference in the number of nuclei stained between the two groups of patients. In conclusion, we highlighted that immunochemistry with the anti-p63 antibody is a potential biomarker to predict the severity of the JoRRP.

Juvenile recurrent respiratory papillomatosis treated with combined erlotinib and celecoxib: Initial report.

Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV). RRP is a clinical challenge because of the high recurrence rate, poor surgery response, extension to tracheobronchial tree and because of the risk of malignancy in some cases. There is no consensus on which adjuvant therapy is better for those patients with highly recurrent course. Because papilloma cells overexpress the epidermal growth factor receptor (EGFR), together with an increased expression of COX-2 and prostaglandin E2, the combination of erlotinib and celecoxib seems plausible, and could be proposed for patients with poor response to previous lines of treatment.

Juvenile-Onset Recurrent Respiratory Papillomatosis Aggressiveness: In Situ Study of the Level of Transcription of HPV E6 and E7.

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is a condition related to HPV 6 and 11 infection which is characterized by the repeated growth of benign exophytic papilloma in the respiratory tract. Disease progression is unpredictable: some children experience minor symptoms, while others require multiple interventions due to florid growth. The aim of this study was to explore the biomarkers of JoRRP severity on a bicentric cohort of forty-eight children. We performed a CISH on the most recent sample of papilloma with a probe targeting the mRNA of the E6 and E7 genes of HPV 6 and 11 and an immunostaining with p16INK4a antibody. For each patient HPV RNA CISH staining was assessed semi-quantitatively to define two scores: 1+, defined as a low staining extent, and 2+, defined as a high staining extent. This series contained 19 patients with a score of 1+ and 29 with a score of 2+. Patients with a score of 2+ had a median of surgical excision (SE) per year that was twice that of patients with a score of 1+ (respectively 6.1 versus 2.8, p = 0.036). We found similar results with the median number of SE the first year. Regarding p16INK4a, all patients were negative. To conclude, HPV RNA CISH might be a biomarker which is predictive of disease aggressiveness in JoRRP, and might help in patient care management.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: N/A Laryngoscope, 130:1186-1194, 2020.

Clinical Significance of Low 2-Methoxyestradiol Levels in Serum and Tissue of Recurrent Juvenile-Onset Laryngeal Papillomatosis.

Objective We aim to explore the correlation between serum and tissue 2-methoxyestradiol (2-ME-2) levels and recurrence of juvenile-onset respiratory papillomatosis (JORRP). Study Design Retrospective cohort studies. Settings Laboratory of Otolaryngology, Department of Head and Neck Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University. Subjects and Methods Sixty-four patients diagnosed with JORRP in our department from January 2007 to December 2012 were enrolled. Patients were divided into recurrence and nonrecurrence groups, with 32 patients in each group. ELISA detected the concentration of 2-ME-2 in serum and tissue samples collected during the first surgical procedure. Mann-Whitney analysis, receiver operating characteristic curves, logistic regression model, and Kaplan-Meier method were used for data processing. Results There was no difference in the serum 2-ME-2 concentration between the groups ( P = .237), while the tissue 2-ME-2 concentration of the recurrent group was significantly lower than that of the nonrecurrence group ( P = .0001). When the area under the curve was 0.752, the cutoff value of tissue 2-ME-2 at 670.02 pg/mL yielded the highest predictive sensitivity (71.9%) and specificity (71.9%). Regrouped by this cutoff point, patients with a lower tissue 2-ME-2 level (n = 26) had shorter disease-free survival and a higher recurrence odds ratio than patients with a higher tissue 2-ME-2 level (n = 38; P = .0408, odds ratio = 7.667). Conclusion A low tissue 2-ME-2 level is associated with a higher recurrence rate of JORRP. Tissue 2-ME-2 may be an effective target for JORRP treatment and a convenient measure for recurrence monitoring.

Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature.

Although juvenile-onset recurrent respiratory papillomatosis (JoRRP) generally involves a benign tumor on the larynx and other respiratory tract areas, almost all patients with this disease require repeated surgical intervention (to prevent airway obstruction during the course of illness) and various adjuvant therapies such as interferon, cidofovir, acyclovir, ribavirin, indole-3-carbinol, HspE7, mumps vaccine, photodynamic therapy, propranolol, cimetidine, and bevacizumab. Some case reports recently described the effectiveness of the quadrivalent human papillomavirus vaccine (HPV4) as an adjuvant therapy. On the basis of these reports, we administered HPV4 to a 2-year-old boy with JoRRP. However, no therapeutic effect was found. A review of the available literature revealed that current evidence for the effectiveness of therapeutic HPV4 and other adjuvant therapies for JoRRP is inconsistent. Therefore, the prophylactic use of currently available HPV vaccine for adolescents is the most effective strategy for preventing not only anogenital cancers but also genital warts, which might be a risk factor for JoRRP among their children in the future.

HLA-DRB1 and HLA-DQB1 alleles in Chinese Han patients with Juvenile-Onset recurrent respiratory papillomatosis.

Juvenile-Onset recurrent respiratory papillomatosis (JORRP) is a rare benign neoplasm of the respiratory mucosa caused by human papilloma virus. Previous studies on the possible associations between HLA alleles and JORRP have shown various results in different ethnic groups. The present study aims to investigate the association between JORRP and HLA class II DRB1and DQB1 alleles in Chinese Han children. We found that the frequencies of HLA-DRB1*03:01 (pc = 0.0378, OR = 4.8) and HLA-DQB1*02:01 (pc = 0.021, OR = 4.8) alleles were significantly higher in patients with JORRP than in controls. In addition, HLA-DRB1*03:01 allele significantly correlated with aggressive JORRP (r = 0.467, p = 0.009). This was the first study on the HLA alleles in Chinese Han patients with JORRP. Future studies are required to further elucidate the correlation of HLA class II alleles and susceptibility to JORRP.

Prolonged remission of juvenile-onset respiratory papillomatosis: a post-expositional role of the tetravalent anti-HPV vaccine?

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is an HPV-related neoplasm affecting primarily the larynx. JORRP often requires repeated surgical debridement, which yield variable but generally moderate remission periods. We report the case of a 6-year-old boy with severe course JORRP since the age of 2, requiring tracheostomy, that underwent prolonged remission and was decannulated some months after administration of the HPV vaccine. The post-exposure use for the anti-HPV vaccine in JORRP is a topic of capital interest but still poorly characterized. Some published cases suggest a potential post-exposure role of the vaccine in JORRP, but prospective multicentric trials are still needed.