Respiratory Papillomatosis Research Articles

Update on HPV-associated head and neck cancers-highlights of the 2024 ASCO Annual Meeting

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), alarge number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented. Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided. The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts. Alarge number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from aphaseIstudy on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to areduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as abreakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP.

Current Practice, Safety and Efficacy of Interventions for Recurrent Respiratory Papillomatosis: Evidence From a UK Registry.

To determine the current practice, safety and efficacy of interventions used in the management of recurrent respiratory papillomatosis (RRP) in the UK NHS. Prospective registry (recruitment between 1st April 2018 and 31st August 2022, retrospective data from 1st January 2015 permitted with consent). Sub-group data-linked to Hospital Episode Statistics for additional follow-up (until 31st July 2022). UK NHS hospitals treating RRP patients. Children and adults diagnosed with RRP and managed in an NHS hospital. Disease severity (Derkay, voice handicap and GRBAS scores), management (type and frequency of surgical and adjuvant intervention) and complications (cancer, death). Three hundred and thirty patients were entered into the registry; 304 (including 65 children) were eligible for analysis. Children had more severe disease than adults (median Derkay score 10 vs. 5). Microdebrider was the most common surgical intervention, particularly in children (86% of children, 49% of adults). Additionally, lasers (CO2, KTP and pulsed dye) were used in 34% of adults. Gardasil was the most common adjuvant therapy (21 children, 23 adults). Procedural complications were rare (10.8% children, 5.9% adults). Five patients developed laryngeal malignancy; there were six deaths during follow-up period. This is the largest UK RRP study to date. RRP is more aggressive in children than adults, and treatment choice differs between age groups. Overall, management was safe with minimal complications reported, and generally effective in maintaining a safe airway. Standardised reporting is required to objectively monitor disease progression and safety over time. NCT03465280, ISRCTN36100560.

Effective control of a severely progressive recurrent respiratory papillomatosis with repetitive cryotherapy.

Effective control of a severely progressive recurrent respiratory papillomatosis with repetitive cryotherapy.

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.

Overview of the ASCO 2024 data on head and neck surgery

At the 2024 international cancer congress of the American Society of Clinical Oncology (ASCO), studies on immuno-oncological therapeutic approaches for head and neck cancers once again took center stage. Following the trend of recent years, neoadjuvant immunotherapy has now reached acentral role, and purely surgical studies have become increasingly scarce. This review article summarizes abstracts presented at the 2024 ASCO Annual Meeting that focus on surgical therapy or in which surgery was asignificant component of the study protocol. As part of the combination therapies, study results on neoadjuvant treatment strategies are also presented. Additionally, promising new developments are discussed, including the treatment of laryngeal papillomatosis, new considerations on the necessary extent of neck dissection, follow-up care for human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), and the prevention of platinum-induced inner ear hearing loss.

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.

Adjuvant treatments for recurrent respiratory papillomatosis: a descriptive review and proposed management guideline in adults.

Adjuvant treatments for recurrent respiratory papillomatosis: a descriptive review and proposed management guideline in adults.

Seroprevalence of human papilloma virus 6, 11, 16 and 18 among pregnant women in Mwanza-Tanzania

IntroductionHigh-risk human-papilloma viruses 16 and 18 (HR-HPV 16 and HR-HPV-18) are well known to be associated with carcinoma of the cervix, head and neck, penis, and anus. Low-risk human papillomaviruses 6 and 11 (LR-HPV 6 and LR 11) infection has been associated with anogenital warts, oral papilloma, and laryngeal papillomatosis in children. HPV infection during pregnancy (HR-HPV and LR-HPV) increases the risk of vertical transmission from infected pregnant women to unborn children. The burden of HR-HPV type 16 and 18 and LR-HPV 6 and 11 is not well documented among pregnant women attending antenatal clinics (ANC). This study determined the seroprevalence and distributions of HR-HPV 16, 18, and LR –HPV 6, 11 antibodies among pregnant women attending ANC at Bugando Medical Centre (BMC) in Mwanza, Tanzania.MethodologyA cross-sectional study involving 255 pregnant women enrolled in obstetrics and gynecology outpatient clinics was conducted between November 2020 and March 2021 at Bugando Medical Centre (BMC) in Mwanza. A structured pre-tested questionnaire was used to obtain patients’ information. Sandwich Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect HPV 6, 11, 16 and 18 specific immunoglobulin G (IgG) from sera. Stata version 15v1 was used for the descriptive data analysis.ResultsThe median age was 27(IQR: 22–31) years. The overall HPV seropositivity for any of the four serotypes was 63.9% (165/255), 95% CI: 58.0-69.7, whereby 37.6%(97/255), 32.2%( 83/255), 15.5% (40/255) and 27.1% (70) were positive for HPV 6, 11, 16 and 18 respectively. Eight participants (3.1%) were positive for all 4 genotypes.ConclusionAbout two-thirds of pregnant women had antibodies against HPV 6, 11 16, and 18 indicating previous HPV exposure. Vaccination programs should be emphasized to reduce the HPV-related manifestations in this population.

Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown. To assess the incremental lifetime outcomes, costs, and cost-effectiveness of integrating peritreatment 9-valent HPV (9vHPV) vaccination in combination with posttreatment surveillance for the prevention of cervical cancer and other HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN vs posttreatment surveillance alone from a UK payer perspective. This economic evaluation used 3 independent Markov model structures. Model inputs for vaccine efficacy, utilities, and costs were obtained from published sources, and cervical cancer screening data were obtained from the National Health Service Cervical Screening Program. Costs were adjusted to 2022 to 2023 reference years. Data were analyzed from October 2022 to September 2023. Peritreatment vaccination with 9vHPV in combination with posttreatment surveillance compared with posttreatment surveillance alone. Clinical outcomes included grade 1, 2, or 3 CIN; cervical cancer; vaginal cancer; vulvar cancer; anal cancer; head and neck cancer; genital warts; and recurrent respiratory papillomatosis. Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold (WTP) of £20 000 (US $26 200) per quality-adjusted life-year (QALY) were estimated. Deterministic sensitivity analysis and probabilistic sensitivity analysis were performed. Vaccination with 9vHPV in conjunction with posttreatment surveillance was cost-effective, with a favorable ICER of £13 789.07 (US $18 064.68) per QALY gained (ie, below the WTP of £20 000 per QALY) vs posttreatment surveillance alone. The resulting ICER was £52 358.01 (US $68 588.99) per HPV-related cancer averted and £64 090 (US $83 958.18) per HPV-related cancer death averted. The ICER was most sensitive to discount rate, incidence of HPV infection, vaccine price, and age at initial treatment for grade 2 or greater CIN. Results of the probabilistic sensitivity analysis showed peritreatment 9vHPV vaccination was cost-effective at the WTP recommended by the UK's Joint Committee on Vaccination and Immunisation (90% of iterations <£30 000 [US $39 300] per QALY) in 100% of iterations. These findings suggest that peritreatment prophylactic 9vHPV vaccination is a cost-effective option for preventing subsequent HPV-attributable diseases in patients surgically treated for grade 2 or greater CIN.

Successful Bevacizumab Therapy in a 25-Year-Old Patient with Recurrent Respiratory Papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a chronic condition caused primarily by human papilloma virus (HPV) types 6 and 11, leading to recurrent growths in the respiratory tract. These types of papilloma can cause significant morbidity due to airway obstruction, often requiring frequent surgical interventions. Traditional treatments, including surgical removal and adjunctive therapies like antivirals and immune modulators, often fail to prevent recurrence, impacting the patient's quality of life. This report presents a 25-year-old female with a long-standing history of RRP, diagnosed at age 2. Despite numerous interventions, including CO2 laser ablations, interferon therapy, HPV vaccination, and a laryngotomy with tracheal reconstruction, the patient continued to experience severe airway obstruction requiring frequent surgeries. In 2023, intravenous therapy with bevacizumab, vascular endothelial growth factor inhibitor was introduced, leading to a significant reduction in the frequency of surgical interventions from 8 to 4 per year. This reduction improved the patient's respiratory function and quality of life, highlighting bevacizumab's therapeutic potential. The case underscores the debilitating nature of RRP and the challenges of its management. Bevacizumab, by targeting vascular endothelial growth factor (VEGF), has shown promise in reducing papilloma growth and the need for frequent surgeries. This case supports the inclusion of bevacizumab as an adjunctive therapy in RRP treatment, warranting further research to confirm its long-term efficacy and safety. Recurrent respiratory papillomatosis is a rare and complex disease that severely impacts patients' quality of life.This case report demonstrates that bevacizumab can significantly reduce surgical interventions in recurrent respiratory papillomatosis (RRP), offering a promising treatment that improves management of this chronic condition.Bevacizumab, already used in treating various diseases by targeting VEGF, shows promise in managing RRP as well, highlighting its potential across multiple conditions and expanding its therapeutic versatility.

1540MO The patient voice: An analysis of real-world data using the recurrent respiratory papillomatosis foundation/CoRDS patient registry (RRPF/CoRDS)

1540MO The patient voice: An analysis of real-world data using the recurrent respiratory papillomatosis foundation/CoRDS patient registry (RRPF/CoRDS)

992O Pembrolizumab for HPV-associated recurrent respiratory papillomatosis

992O Pembrolizumab for HPV-associated recurrent respiratory papillomatosis

Quantifying Bevacizumab Efficacy in Recurrent Respiratory Papillomatosis.

To develop and validate a novel method for quantifying the efficacy of Bevacizumab (Bev) in treating Recurrent Respiratory Papillomatosis (RRP), and to evaluate the clinical outcomes of a three-dose Bev induction therapy followed by surgical intervention. Twenty-one RRP patients treated with a three-dose Bev regimen were included. A novel efficacy evaluation method using ImageJ software was developed to calculate the standardized lesion volume from laryngoscopic images. This was compared with the Derkay score. Clinical outcomes, including reduction rate, cumulative reduction rate, efficacy grading, recurrence, and adverse reactions, were analyzed. In the study cohort, the reduction rate was significantly higher after the first treatment compared with subsequent treatments. The overall response rate increased from 75% after the first treatment to 100% after the third. Among patients with localized lesions who underwent surgery, 76% experienced recurrence with a mean recurrence time of 114.23 days. Most recurrent lesions were smaller than at baseline. Adverse reactions included increased blood pressure in seven patients, which resolved without intervention. The new method showed a significant positive correlation with the Derkay score. In conclusion, based on the above findings, systemic Bev treatment for RRP is a safe and effective therapeutic approach, though further research is needed. Moreover, the new efficacy evaluation method we developed can significantly aid in studying the effectiveness of Bev treatment for RRP. 2 Laryngoscope, 2024.

Mucosal Injection of the Silicon Phthalocyanine Pc 4 in a Rabbit Model-A Pilot Study.

The silicon phthalocyanine Pc 4 is a photosensitizing agent previously shown to be a promising treatment for cutaneous neoplasms using photodynamic therapy (PDT). Based on prior preclinical studies, we believe Pc 4-PDT has potential as a targeted treatment of human recurrent respiratory papillomatosis or laryngeal leukoplakia by direct injection into mucosal surfaces. This was a proof-of-concept pilot study assessing direct mucosal injection of Pc 4 into buccal and vocal fold mucosae in a rabbit model. Five New Zealand white rabbits underwent tattooing of bilateral buccal mucosae to delineate injection sites, followed by submucosal injections of control and Pc 4 solutions. Rabbits were monitored for post-injection tolerance. Punch biopsies were obtained from injected mucosa and assessed histopathologically. Once the buccal mucosa was found to be tolerant, vocal folds of three rabbits were injected. The rabbits were then sacrificed, and laryngeal tissue was assessed histopathologically. All rabbits tolerated injection of Pc 4 and control solutions into buccal mucosa with no evidence of gross visual inflammatory changes and no changes in behavior or masticatory function. Histopathologic analysis of Pc 4 injected buccal and control mucosal tissue revealed mild focal histological changes and no stigmata of diffuse inflammatory reactions. The histopathologic analysis of Pc 4 injected into laryngeal tissue revealed similar findings with addition of mild eosinophilia in one sample. Direct mucosal injection of Pc 4 in rabbit buccal and vocal fold mucosae appears to be well tolerated with no gross inflammatory changes, and only mild histopathologic inflammatory changes observed. NA Laryngoscope, 2024.

Recurrent Laryngeal Papillomatosis in Denmark from 1994 to 2021: A Nationwide Register Study.

The aim of this study is to describe the incidence and demographics of laryngeal papillomatosis (LP) in Denmark, including sex and age distribution, recurrence rates, and HPV subtypes, using a new method of register identification. The data were extracted from the Danish Pathology Data Bank using SNOMED codes instead of the usual method using ICD codes from the Danish National Health Register. The derived pathology records were manually verified by three medical doctors. The study period was 1994-2021. Patients were categorized according to age as either juvenile-onset RRP (JoRRP) if <18 years or adult-onset RRP (AoRRP) if 18 years or older. We identified 1819 RRP patients (JoRRP: 56; AoRRP:1763). The overall incidence per 100,000 inhabitants were 0.17 for JoRRP and 1.45 for AoRRP. The vast majority (72%) of the patients were male, but there was no significant difference in age at onset of RRP or recurrence rates between the sexes. Children below 3 years of age had the highest recurrence probability. Extracting data using SNOMED codes resulted in a positive predictive value of 99% regarding total number of biopsies and 98% regarding individuals. The incidence decreased throughout the study period. Comparable incidence and recurrence rates of RRP were found between Denmark and Norway. In this study, the Danish Pathology Register was found to be a highly valuable method for identifying LP patients. The effect of the nationwide HPV vaccination program can be evaluated using this method as the vaccinated cohort is starting to grow older and reproduce. Retrospective registry-based national cohort study, level of evidence 3 Laryngoscope, 2024.

Forecasting Disease Burden with a Dynamic Transmission Model of Human Papillomavirus and Recurrent Respiratory Papillomatosis in the United States.

Juvenile- and adult-onset recurrent respiratory papillomatosis (JORRP and AORRP) are rare but serious conditions that are caused by oral human papillomavirus (HPV) infections. The proliferation of wart-like growths throughout the respiratory tract can result in medical problems, including death. The current treatment scheme is surgery, though prevention of HPV infection through vaccination is available. A previously developed model for JORRP and AORRP was adapted to the United States using data on disease burden and HPV infection. The model was validated against post-vaccination reductions in disease and used to forecast the future burden of JORRP and AORRP, estimating the impact that HPV vaccination will have on these diseases. Between 2007 (the beginning of HPV vaccination in the US) and 2021, this model estimates that approximately 1393 lives, 22,867 Quality-Adjusted-Life-Years, and over USD 672 million in treatment costs have been saved by HPV vaccination. There is also a substantial reduction in JORRP and AORRP burden, with a 95% reduction in incidence by 2040. Moreover, between 2040 and 2121, the model predicts 3-11 total cases of HPV6/11-related JORRP in the US, and 36-267 total cases of HPV6/11-related AORRP. HPV vaccination in the United States has driven, and will continue to drive, substantial reductions in the public health and economic burden of HPV6/11-related JORRP and AORRP.

Step treatment of invasive recurrent respiratory papillomatosis in children: a case report

Step treatment of invasive recurrent respiratory papillomatosis in children: a case report

The role of human papillomavirus in laryngeal cancer and recurrent respiratory papillomatosis: epidemiological and clinical aspects

In the recent decade, the number of laryngeal cancer cases increased worldwide by 23 %. Currently, laryngeal cancer morbidity and associated mortality do not show statistically significant trends toward a decrease. The main risk factors for laryngeal carcinoma are smoking, alcohol consumption, human papilloma virus (HPV) infection, recurrent respiratory papillomatosis, and genetic predisposition.Aim. To evaluate the incidence and role of HPV in etiology and clinical course of laryngeal cancer and recurrent respiratory papillomatosis.Analysis of the available literature sources published in the Medline, Pubmed, and eLibrary databases was performed. The review is based on 59 of 584 identified scientific studies. Frequency of HPV detection in laryngeal cancer tumor tissue varies and is associated with the studied country’s geographical location. The incidence of these viruses in tumor tissue varies between 2.7 and 62.6 %. Genotype 16 human papilloma virus is more common in women between the ages of 31 and 40 years and is mostly located near the glottic aperture. Genotype 6 and 11 human papilloma viruses promote development of recurrent respiratory papillomatosis of the larynx and are detected in 0–87.5 % of cases. It is noted that in patients with HPV-positive neoplasms of the larynx, better response to radiation therapy and higher survival rates are observed compared to patients without the virus. In countries where national programs of vaccination against HPV infection have been implemented, a significant decrease in the incidence of recurrent respiratory papillomatosis is observed.The incidence of HPV in laryngeal cancer and recurrent respiratory papillomatosis varies. The role of these viruses in carcinogenesis has not yet been fully understood. Clinical course of HPV-associated laryngeal carcinoma is more favorable than HPV-free laryngeal carcinoma, however, this statement requires further confirmation. Evaluation of the results of programs of vaccination against HPV and their effect on recurrent respiratory papillomatosis and laryngeal cancer morbidity is important.

A Consensus Statement on the Administration of Systemic Bevacizumab in Patients with Recurrent Respiratory Papillomatosis.

To provide detailed guidance on the administration of systemic bevacizumab in patients with recurrent respiratory papillomatosis (RRP) based on a detailed review of the scientific literature and a consensus of experts with real-world clinical experience. A bevacizumab consensus working group (N = 10) was composed of adult and pediatric otolaryngologists, adult and pediatric oncologists, and a representative from the RRP Foundation (RRPF), all with experience administering systemic bevacizumab in patients with RRP. After extensive review of the medical literature, a modified Delphi method-based survey series was utilized to establish consensus on the following key areas: clinical and patient characteristics ideal for treatment candidacy, patient perspective in treatment decisions, treatment access, initial dosing, monitoring, guidelines for tapering and discontinuation, and reintensifying therapy. Seventy-nine statements were identified across nine critical domains, and 45 reached consensus [clinical benefits of bevacizumab (3), patient and disease characteristics for treatment consideration (7), contraindications for treatment (3), shared decision-making (incorporating the patient perspective) (5), treatment access (3), initial dosing and administration (8), monitoring (7), tapering and discontinuation (6), and reintensification (3)]. This consensus statement provides the necessary guidance for clinicians to initiate systemic administration of bevacizumab and represents a potential paradigm shift toward nonsurgical treatment options for patients with RRP. 5 Laryngoscope, 2024.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis

ObjectiveThis study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). MethodsReview the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. ResultsA total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. ConclusionIn conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).