Treatment outcomes of recurrent respiratory papillomatosis : Retrospective analysis of juvenile and adult cases.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease of viral etiology which is characterized by multiple, recurrent growth of papillomas in the aerodigestive tract. MATERIALS AND METHODS: The surgical outcomes and the recurrence rates of 106 patients with RRP of the larynx were analyzed. The patients were treated at the University of Magdeburg between 1983 and 2014. The surgical outcomes of conventional and laser surgery regarding time to relapse and complications were compared. In addition, the influence of the quadrivalent vaccine Gardasil® on the disease was analyzed in 10 patients. RESULTS: Children with RRP had a statistically significant greater number of surgeries throughout their lifetimes compared to adult patients. There were no differences between the adult (n = 79) and juvenile (n = 27) groups in the time to relapse and the number of surgeries/year. The time to relapse and number of procedures/year were not influenced by the various surgical methods. Complications after conventional and laser surgery were not statistically different between the two groups. Serious complications and the need for a tracheotomy were only reported after conventional surgery. In the 10 patients who were immunized with Gardasil®, a statistically significant lower number of surgeries/year after vaccination was achieved. CONCLUSION: RRP is a rare disease. Treatment requires experience and may be very difficult. The analysis of the course of the disease has shown that the treatment of choice is surgical excision with the CO2 laser combined with the quadrivalent or polyvalent vaccine. Consequent vaccination of both boys and girls has the potential to reduce the occurrence of RRP.

[Treatment outcomes of recurrent respiratory papillomatosis : Retrospective analysis of juvenile and adult cases. German version]. / Behandlungsergebnisse bei rezidivierender respiratorischer Papillomatose : Retrospektive Analyse juveniler und adulter Fälle.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease of viral etiology which is characterized by multiple, recurrent growth of papillomas in the aerodigestive tract. MATERIALS AND METHODS: The surgical outcomes and the recurrence rates of 106 patients with RRP of the larynx were analyzed. The patients were treated at the University of Magdeburg between 1983 and 2014. The surgical outcomes of conventional and laser surgery regarding time to relapse and complications were compared. In addition, the influence of the quadrivalent vaccine Gardasil® on the disease was analyzed in 10 patients. RESULTS: Children with RRP had a statistically significant greater number of surgeries throughout their lifetimes compared to adult patients. There were no differences between the adult (n = 79) and juvenile (n = 27) groups in the time to relapse and the number of surgeries/year. The time to relapse and number of procedures/year were not influenced by the various surgical methods. Complications after conventional and laser surgery were not statistically different between the two groups. Serious complications and the need for a tracheotomy were only reported after conventional surgery. In the 10 patients who were immunized with Gardasil®, a statistically significant lower number of surgeries/year after vaccination was achieved. CONCLUSION: RRP is a rare disease. Treatment requires experience and may be very difficult. The analysis of the course of the disease has shown that the treatment of choice is surgical excision with the CO2 laser combined with the quadrivalent or polyvalent vaccine. Consequent vaccination of both boys and girls has the potential to reduce the occurrence of RRP.

Determination of the complete genome and functional analysis of HPV6 isolate VBD19/10 from a patient with aggressive recurrent respiratory papillomatosis.

Human papillomavirus (HPV) types 6 and 11 are the aetiological agent of recurrent respiratory papillomatosis (RRP). The complete genome of an HPV6 isolate with a 170 base pair (bp) duplication identified within the long control region (LCR) from a patient with aggressive recurrent respiratory papillomatosis was determined. The promoter sequence from the HPV LCR including the 170 bp duplication was placed upstream of a heterologous reporter gene and the activity of the reporter gene product determined using transfected cells. In total, mutations were observed at 157 nucleotide positions of the complete genome and included nucleotide substitutions, deletions and insertions, resulting in amino acid changes at 43 residue positions. Reporter gene activity using an HPV-derived LCR region with a 170 bp duplication was significantly higher than that using an HPV-derived LCR region with no duplication within this region. The results suggest that novel HPV variants warrant further investigation for potential biomarkers of aggressive disease.

Our experience in developing and operating the Airway Intervention Registry for Recurrent Respiratory Papillomatosis (AIR-RRP): national data collection [version 2; peer review: 2 approved].

Recurrent respiratory papillomatosis (RRP) is characterised by benign wart-like growths in the respiratory tract caused by the human papillomavirus (HPV). These warts vary in size and grow quickly, causing voice changes and airway obstruction. Whilst the condition is rare, RRP is more common and aggressive in children. There is currently no curative treatment for HPV, therefore RRP is managed by maintaining a safe airway and a serviceable voice by repeated surgery to remove the growths. A lack of specific diagnostic codes prevents reliable case ascertainment of RRP from routine administrative databases such as Hospital Episode Statistics. In 2017 a cross-sectional survey identified 918 RRP patients in the UK, half of whom had received surgical intervention for RRP in the previous 12 months with 16 different interventions. Randomised controlled trials for RRP interventions are difficult due to the rarity of the disease, variation in severity and progression and non-standard care across the NHS. Consequently, there is a lack of definitive efficacy and safety evidence. The only national guidance for RRP interventions is "Radiofrequency cold ablation for respiratory papillomatosis" (NICE IPG434, 2017) which recommended further data collection due to lack of evidence. However, due to the wide variation in RRP management across the NHS, clinical opinion favoured that any data collection should include a comparison of safety and efficacy of all RRP interventions in order to advise which improved patient outcomes and quality of life. To address lack of evidence, and inform the future care of RRP patients, we developed a registry and used it to collect real-world data from patients receiving treatment for RRP in NHS hospitals across the UK. The purpose of this paper is to share lessons learned from this national data collection exercise to inform future clinical registry development.

Smoking and Carcinoma Trends in Recurrent Respiratory Papillomatosis Patients.

INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a chronic disease of the upper respiratory tract caused by human papillomavirus types 6 and 11. The disease course is characteristically unpredictable, ranging from spontaneous remission to aggressive, recurrent disease. Thus, management is often challenging and requires unique approaches tailored to each individual patient. While recent literature has described risk factors for more aggressive disease, few sources have investigated the impact of smoking on RRP disease course and risk for malignant transformation. METHODS: A retrospective chart review was conducted for adult RRP patients evaluated at an academic tertiary care center between 2005 and 2020. A total of 188 patients were identified. Demographic and clinical data were collected, including smoking and alcohol history, HPV subtype, history of dysplasia and/or carcinoma, voice handicap index scores, Derkay scores, debulkings (in office and operating room), and days to papilloma recurrence. RESULTS: Malignant degeneration in RRP occurred in 16.3% of smokers and 3.6% of nonsmokers. Smokers who developed carcinoma had less debulkings per years of evaluation than those not developing carcinoma (0.21 vs 0.92, P = .004). Additionally, patients that either presented with or developed carcinoma during their course had a higher pack-year smoking history (18.0 vs 12.21, P = .0002). No difference in days to recurrence or inter-surgical interval was demonstrated between smokers and nonsmokers. CONCLUSIONS: The report demonstrates that smoking can increase the risk of malignant transformation in RRP patients.

Long-Term Follow-up of Parenteral Bevacizumab In Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: The clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non-surgical therapies are emerging in hopes of non-operative disease control. This retrospective review analyzes long-term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP. METHODS: Twenty-three patients with known RRP who have been receiving off-label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated. RESULTS: Patients have been followed for an average of 791.43 (21-1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long-term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14-week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events. CONCLUSION: Parenteral bevacizumab remains a well-tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725-2733, 2023.

Spontaneous Regression of Recurrent Respiratory Papillomatosis with HPV Vaccination: A Case Study.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is characterized by recurrent laryngeal papillomas and treated with repeated surgical excision. The human papillomavirus (HPV) vaccine prevents infection with strains of HPV unrelated to RRP, and has recently been shown to increase the interval between surgeries when used as an adjuvant. The objective of this study was to report one case from our institution in which HPV vaccination was found to induce spontaneous regression of disease, absent of surgical intervention or use of other adjuvants. STUDY DESIGN: Retrospective case study. METHODS: Records of one patient with RRP receiving partial HPV vaccination was reviewed with attention to videolaryngostroboscopic findings, Derkay score, need for surgical intervention, and voice quality. RESULTS: Spontaneous regression of disease after vaccination was seen in this patient, as evidenced by reduced tumor burden and decreased voice handicap index. The patient was a 30-year old female, who had improved disease burden and voice quality after one dose and total resolution of disease following the second dose. Vaccine administration was the sole therapeutic mechanism. CONCLUSIONS: These findings suggest that HPV vaccination can treat RRP without surgical intervention. Further studies are needed to investigate the underlying mechanism of disease regression and which patients may benefit most. We believe that HPV vaccination for all patients with RRP, even over the age of 45 years, may decrease treatment costs for individuals and the healthcare system overall.

Manifestations of Human Papillomavirus in the Head and Neck.

Human papillomavirus (HPV)-positive oropharyngeal cancers (OPC) are increasing due to infection with the virus. Most of the patients diagnosed with HPV-positive OPC are white men with numerous lifetime sexual partners who have smoked marijuana excessively. In working up the patient, it is important to obtain an extensive history and physical examination and obtain proper imaging. Once a full workup is done, it is crucial to engage a multidisciplinary team in treatment and continue following-up with the patient through posttreatment surveillance. Administering the HPV vaccine at a young age may help reduce the increasing rate of HPV-positive OPC in the future.

Presenting Symptom as a Predictor of Clinical course in Juvenile Onset Recurrent Respiratory Papillomatosis.

OBJECTIVE/HYPOTHESIS: Determine if the presentation of voice versus airway symptoms at the time of diagnosis of juvenile recurrent respiratory papillomatosis (JORRP) correlates with treatment and outcomes. STUDY DESIGN: Original report, Retrospective review. METHODS: Twenty year retrospective review of all patients with JORRP presenting at any time in treatment to a single tertiary children's hospital between 1997 and 2017. RESULTS: Fifty-four patients presented with a diagnosis of JORRP during the 20 year study period. Of these, 32 were female and 22 were male. African American children made up the majority of the patients (65%), with 19% identifying as Caucasian, 9% Hispanic, and 7% Asian. Fifteen of the children presented initially to the ENT clinic (87% with hoarseness), 12 to the emergency department (92% with airway concerns), 11 to the voice clinic, and the remaining 12 at outside hospitals or clinics and care were transferred. Voice symptoms, namely hoarseness, was the presenting symptom in 31 (57%), airway symptoms, namely respiratory distress or stridor was predominate in 17 (32%), and the presenting symptom was unknown in six cases (11%). Children presenting with airway symptoms were younger at presentation (median 2.1 years, range 0.38-8.77 years) than those presenting with voice symptoms (median 6.7 years, range 0.98-15.13 years), and after adjusting for age underwent a greater number of surgeries in the first year to control disease. CONCLUSIONS: Patients who present with airway symptoms present younger and have an increased number of surgeries in the first year compared to those presenting with voice complaints. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1670-1675, 2021.

Multi-Year Effect of Human Papillomavirus Vaccination on Recurrent Respiratory Papillomatosis.

OBJECTIVE: To examine whether human papilloma virus (HPV) vaccination in combination with surgical resection could suppress recurrence for an extended period of time in patients with recurrent respiratory papillomatosis (RRP). METHODS: In a prospective case series, data of patients who received combination therapy comprising surgery and quadrivalent HPV vaccination (Gardasil; Merck & Co., West Point, PA) were collected. Patients were followed up for RRP from March 2012 to July 2018 in an academic tertiary care center. The patients comprised 16 adults with RRP who were observed for >12 months after HPV vaccination, and whose HPV-DNA status was tested before and for >12 months after completion of combination therapy. The outcomes of this study were the severity score of larynx disease, tumor incidence rate, and relationship between this rate and HPV-DNA negative conversion after therapy. RESULTS: The severity score of laryngeal disease significantly decreased from before combination therapy to the time of final examination (P = 0.00045). The tumor incidence rate decreased to approximately 20% during the period from 12 to 47 months after HPV vaccination. Regarding HPV-DNA status in the final test results of each patient, 12 of 16 (75%) patients showed negative conversion; these 12 were significantly less likely to experience recurrence than patients who persistently tested positive for HPV-DNA during the period between 12 and 47 months after vaccination. CONCLUSION: HPV vaccination prevented recurrence associated with RRP surgery for 4 years in 80% of patients. This may be an effective adjuvant therapy, and HPV-DNA negative conversion after HPV vaccination might predict prevention of recurrence. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:442-447, 2020.

Current and future management of recurrent respiratory papillomatosis.

Objectives: Recurrent respiratory papillomatosis (RRP) is a chronic disease of the respiratory tract that occurs in both children and adults. It is caused by the human papillomavirus (HPV), in particular low-risk HPV6 and HPV11, and aggressiveness varies among patients. RRP remains a chronic disease that is difficult to manage. This review provides perspectives on current and future management of RRP. Results: The current standard of care is surgical excision, with adjuvant therapies as needed. Surgical management of RRP has evolved with the introduction of microdebriders and photoangiolytic lasers; the latter can now be used in the office setting. Numerous adjuvant pharmacologic therapies have been utilized with some success. Also, exciting preliminary data show that HPV vaccines may prolong the time to recurrence in the RRP population. There is also optimism that wide-spread HPV vaccination could reduce RRP incidence indirectly by preventing vertical HPV transmission to newborns. Conclusion: To date, the biology of RRP is not well understood, although it has been noted to become more aggressive in the setting of immune suppression. Additional research is needed to better understand immune system dysfunction in RRP such that immunomodulatory approaches may be developed for RRP management. Level of Evidence: 4.

Human Papillomavirus (HPV) Genotype Distribution in Patients with Recurrent Respiratory Papillomatosis (RRP) in Iran

Background: Currently, recurrent respiratory papillomatosis (RRP), common laryngeal warts in the upper airway systems of children and adults are on the increase. Human papillomaviruses (HPVs) are suspected as causative agents. This study concerned HPV incidence and genotype distribution in Iranian RRP patients. Methods: Specimens were collected from RRP patients referred to hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran, from Dec 2014 to Feb 2016 in a cross sectional study. After DNA extraction with an QIAamp® DNA FFPE Tissue Kit, conventional PCR was performed and products were sequenced. INNO-LiPA HPV Genotyping Extra assays as another method for genotyping were conducted. CLC Main Workbench 5 and MEGA6 software as well as SPSS v.20 were used for further analysis. Results: Of the total of 12 patients, 6 (50%) were male. Total mean age (y) ± SD was 9.8±6.3. All RRP patients suffered from HPV infection, with HPV-6 found in 75% (9/12) and HPV-11 in 16.7% (2/12) and one co-infection by both HPV-6 and 11. Statistically, there were no correlations between demographic variables and HPV infection. Conclusion: The major cause of RRP is HPV genotypes 6 and 11 increasing the risk of a requirement for medical interventions. Broader studies are needed to clarify the major risk factors in RRP patients.

Möglichkeiten und Grenzen der Fluoreszenzdiagnostik und photodynamischen Therapie : Teil 2: Photodynamische Therapie.

In photodynamic therapy, neoplastic tissue is damaged and subsequently killed by the targeted illumination of previously photosensitized cells. This review is aimed at a comprehensive, but still easily understandable, presentation of all of the aspects of these methods relevant to ENT-doctors. Initially, an explanation of the clinically relevant difficulties in the therapy of (pre-)malignant lesions of the head and neck region, a historical synopsis of the development of this method and an illustration of the biophysical basics is given. The main part of the publication, however, revolves around the description of the current status of research and a presentation of internationally approved methods. At the end, a short overview of possible future developments in this field is given.