Recurrent Respiratory Papilloma Research Articles

Recurrent Respiratory Papilloma of the Larynx

Recurrent respiratory papilloma (RRP) is a common benign neoplasm that most commonly affects the larynx. Caused primarily by human papilloma virus (HPV) types 6 and 11, RRP affects both children and adults; juvenile-onset RRP is thought to be related to HPV exposure during childbirth, whereas adult-onset disease has been hypothesized to be related to sexual contact.1Aaltonen L.M. Rihkanen H. Vaheri A. Human papillomavirus in larynx.Laryngoscope. 2002; 112: 700-707https://doi.org/10.1097/00005537-200204000-00020Crossref PubMed Scopus (83) Google Scholar Symptoms of RRP are typically voice or airway related. Adults tend to experience voice changes, primarily because of impairment of vocal fold vibration in the setting of papilloma along the membranous vocal folds. In children, in whom lesions tend to grow more quickly, airway narrowing may present with stridor in addition to voice changes. Direct or indirect laryngoscopy is standard work-up. Flexible fiberoptic or distal chip scopes may reveal heaped, irregular lesions of the glottis (Figure 1A) or supraglottis, and filters (eg, narrow-band imaging) (Figure 1B) may help to reveal intraepithelial capillary loops. Biopsy remains the criterion standard for diagnosis. Figure 2 illustrates typical findings, including a higher-power image of a cellular papillary frond with viral cytopathic effects and corresponding chromogenic in situ hybridization for low-risk HPV type 6/11.2Venkatesan N.N. Pine H.S. Underbrink M.P. Recurrent respiratory papillomatosis.Otolaryngol Clin North Am. 2012; 45 (671-94, viii-ix. https://doi.org/10.1016/j.otc.2012.03.006)Abstract Full Text Full Text PDF Scopus (89) Google Scholar Treatment includes excision or ablation with cold technique, photoangiolytic lasers, or microdebriders, with maximal conservation of the subepithelial vocal fold tissue. Recurrent respiratory papilloma routinely recurs, and so adjunct treatments with cidofovir and bevacizumab are advocated for recalcitrant cases.3Pogoda L. Ziylan F. Smeeing D.P.J. Dikkers F.G. Rinkel R.N.P.M. Bevacizumab as treatment option for recurrent respiratory papillomatosis: a systematic review.Eur Arch Otorhinolaryngol. 2022; 279: 4229-4240https://doi.org/10.1007/s00405-022-07388-6Crossref Scopus (3) Google Scholar Emerging evidence suggests that HPV vaccination, even in those already affected, may be beneficial in reducing the severity of disease.4Ponduri A, Azmy MC, Axler E, et al. The efficacy of human papillomavirus vaccination as an adjuvant therapy in recurrent respiratory papillomatosis. Laryngoscope. Published online January 18, 2023. https://doi.org/10.1002/lary.30560.Google Scholar The authors report no competing interests.

An Experimental Model of Human Recurrent Respiratory Papillomatosis: A Bridge to Clinical Insights.

To investigate the growth pattern of recurrent respiratory papilloma (RRP) implants on chicken embryo chorioallantoic membranes (CAMs) and to evaluate possible associations between the clinical course of the disease and the behavior of experimentally implanted RRP tumors. Experimental study. Fresh 172 RRP tissue samples from 12 patients were implanted onto chick embryo CAMs. Morphological and morphometric analysis of the experimental CAM and chorionic epithelium was performed. The microvascular network of the CAM with the RRP implant was investigated under the effect of fluoresceinated anionic dextran. The peculiarities of the clinical course of the disease were evaluated. The implanted RRP tissue samples survived on CAMs in 86% of cases, retaining their essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM and the chorionic epithelium, but none of the RRP implants crossed the basement membrane of the hosting CAM. A "crawling film" of acellular material with newly formed papilloma sprouts located on the outer chorionic epithelium of the CAM was detected. Direct association between a recurrence rate of RRP and the number of newly formed papilloma sprouts around the implanted tumor on CAMs was revealed. The chicken embryo CAM-based model is appropriate for investigations of RRP and facilitates the understanding of tumor biology and the clinical course of the disease, thus providing the basis for further research and acceleration of the identification and development of new specific therapeutic compounds that limit the spread and recurrence of RRP. N/A Laryngoscope, 131:E914-E920, 2021.

Correlation of Aggressivity Papilloma Recurrent Respiratory Tract With Human Papillomavirus Types 6 And 11

Background : Recurrent respiratory tract papilloma (PSPB) is a viral disease that correlated with an airway exophthalmia lesion. Papilloma is primarily caused by human papillomavirus (HPV) types 6 and 11 which are classified as low-risk HPV. Reports indicate that patients with the HPV-11 experience more aggressive course of the disease than HPV-6. Patients are often diagnosed at a younger age, the longer duration, require more frequent surgery and rare diseases of the disease when compared with those caused by HPV-6.Objectives : To investigate the correlation of aggressiveness of PSPB with HPV-6 and 11.Methods : Fifteen samples were conducted in the Outpatient Unit of Otorhinolaryngology and the Lotus Inpatient Installation of Dr. Soetomo General Hospital from December 2012 to March 2013 then determine the disease aggressiveness. PCR examination was done at the Tropical Disease Institute of Universitas Airlangga. Aggressive correlation of disease with HPV type was tested using Chi-Square.Results : Fifteen patients were enrolled that divided; the male was 10 and female was 5. The mean annual number of operations was 2.8 ± 1.27 and 9 patients reported more than 3 surgeries each year. 10 patients had distal papilloma and 11 patients had a history of tracheostomy. PSPB was found in 12 patients, HPV-11 was 9 patients and HPV-6 was 6 patients. Chi-square test results showed no significant results with p = 0.525.Conclusion : There was no correlation between PSPB aggression with HPV-6 and 11

Surgical Treatment for Recurrent Respiratory Papilloma: Strategy of our Department and the Value of Day Surgery

Surgical Treatment for Recurrent Respiratory Papilloma: Strategy of our Department and the Value of Day Surgery

Histologic effect of the potassium-titanyl phosphorous laser on laryngeal papilloma.

ObjectivesTissue effects occurring with potassium‐titanyl phosphorous (KTP) laser treatment are difficult to quantify due to the multiple variables that affect not only the fluence (energy delivered) but also the laser–tissue interaction. This histopathologic analysis of recurrent respiratory papilloma (RRP) removed after treatment with KTP laser therapy permits correlation of histologic effect with method of laser treatment.MethodsThe histopathology of RRP resected specimens in a single patient was compared following treatment with KTP laser in contact and non‐contact modes as documented with intraoperative photography and video imaging.ResultsEpithelial‐sparing injury selective to the microvasculature was identified on histopathologic assessment of a specimen treated with noncontact angiolysis. Highly cauterized papillomatous epithelium without identifiable vascular structures was identified on tissue removed after treatment with the KTP laser in contact mode.ConclusionThe histopathologic assessment of acute KTP laser effect on papilloma permits correlation between technique of application and tissue effect. Similar assessments may be helpful to modify dosimetry for individual patients requiring repeated treatment and may also assist in refining the development of existing KTP laser treatment classification systems.Level of Evidence4

Research status of human papillomavirus vaccine for prevention and treatment of respiratory papillomatosis

Recurrent respiratory papilloma (RRP) is closely related to human papillomavirus (HPV) infection and is the main pathogenic factor. At present, HPV vaccine injection is a new method to control RRP, and its efficacy has been confirmed by many clinical trials. The development and application of HPV vaccine is bound to bring new development to the treatment of RRP. This article reviews the status of HPV vaccine in clinical RRP treatment.

Economic impact of recurrent respiratory papillomas in a UK adult population

To calculate the financial burden of recurrent respiratory papilloma. This study is UK-based, where up until now no financial estimates have been calculated for this group of patients. Recurrent respiratory papilloma is caused by the human papilloma virus (subtypes 6 and 11). The burden for the patient and the healthcare system is significant given the recurrent nature of the disease. Data were collected, using a questionnaire completed during routine clinical follow up, from a single centre managing recurrent respiratory papilloma in Glasgow, Scotland. Cost information was sourced from the Scottish Government's Information Services Division. Fourteen patients with active recurrent respiratory papilloma between 2013 and 2014 were identified. The direct measurable cost to NHS Greater Glasgow and Clyde amounted to £107 478. Recurrent respiratory papilloma is a benign condition, but the financial implications of diagnosis are significant. Recurrent respiratory papilloma has a natural history of relapse and remission, and patients may require healthcare input over a period of several years.

OR Management of Recurrent Respiratory Papilloma

Surgical management of recurrent respiratory papillomatosis has depended upon surgical removal and debulking of disease to maintain a patent airway and preserve vocal function. Over time, this has evolved from cold instrumentation alone to microscope-guided laser ablation. Powered instrumentation in the form of microdebriders has also come to serve an important role for the rapid removal of exophytic, airway obstructive disease. With this evolving technologic sophistication, the surgical paradigm has progressed from maintaining a patent airway to maintaining vocal function. This chapter will discuss the evolution of surgical management, the considerations for airway management and operative anesthesia, and will finally discuss current adjuvant medical therapies and imaging modalities that seek to limit disease recurrence and enhance detection and surgical management.

Office-based Management of Recurrent Respiratory Papilloma.

This review will highlight the indications and benefits of office-based therapy for recurrent respiratory papillomatosis (RRP) and discuss the utilization of photo-dynamic lasers and adjuvant medical therapy in office-based settings. Office-based management of RRP allows for more timely interventions, is preferred by the majority of patients, and negates the risk of general anesthesia. Current literature argues for the utilization of KTP laser over CO2 laser for office-based treatment of RRP. Medical therapies for RRP are limited, but agents such as bevacizumab are promising and have been shown to reduce disease burden. Medical therapies that can induce disease remission are still needed. Office-based procedures save time and healthcare expenses compared to like procedures in the operating room. However, the increased frequency for office-based procedures predicts similar overall healthcare costs for office-based and OR laser excision of RRP. Office-based management of RRP is a feasible and well-tolerated strategy in appropriately selected patients with adequate local anesthesia.

The Use of the Quadrivalent Human Papillomavirus Vaccine (Gardasil) as Adjuvant Therapy in the Treatment of Recurrent Respiratory Papilloma

To examine the effect of the quadrivalent human papillomavirus vaccine, Gardasil, on the disease course of patients with recurrent respiratory papillomatosis (RRP). A retrospective chart review of patients with RRP was conducted and 20 patients were selected who had received the Gardasil vaccine as part of their treatment. Efficacy was assessed by calculating the intersurgical interval (ISI) before and after receiving the vaccine, as well as number of complete and partial remissions. Analysis of all patients found a significant increase in the ISI of 3.1 months (95% confidence interval [CI]: 1.02-5.19, P=0.0061). Male patients experienced an increase in the ISI of 4.2 months (95% CI: 1.6-6.7, P=0.0048). Female patients had a nonsignificant increase in ISI of 1.2 months (95% CI: 3.1-5.4, P=0.51). Eight patients (40%; six male and two female) experienced complete remission. Five patients (25%) overall (three male and two female) experienced partial remission. In total, complete or partial remission was achieved in a total of 13 (65%) patients (nine male and four female). The Gardasil vaccine can modulate the severity of RRP and induce remission in some patients. The effect was much greater in males and in females in low estrogen states.

Glottic Papilloma in Pregnancy

ABSTRACT Respiratory papilloma (RP) is the most common benign neoplasm of the larynx, both in children and in adult. The etiology of recurrent respiratory papilloma is human papilloma virus (HPV), which has propensity to lay in normal epithelium, hence the high rate of recurrence. We report a case of an adult onset large glottic papilloma seen in a female with 3rd trimester pregnancy, which was excised under microscope under local anesthesia. The effect of pregnancy and latest modalities of treatment are discussed in this article. How to cite this article Mittal R, Verma H, Mathur N, Bhuie HS. Glottic Papilloma in Pregnancy. Int J Phonosurg Laryngol 2014;4(1):43-44.

Peri-operative management on juvenile recurrent respiratory papillomatosis

To investigate the safety of peri-operative management on children with juvenile recurrent respiratory papilloma (JORRP). A retrospective analysis was conducted on preoperative assessment, anesthesia methods and options, operative procedure, and postoperative airway maintenance in 28 JORRP children aged from ten months to seven years old. A total of 148 times of surgery was performed on these 28 children. One hundred and nine JORRP children graded one and two-degree dyspnea underwent surgery within 24 hours and were intubated successfully in the first attempt after intravenous induction. Thirty-nine emergency operations were performed in the children graded three and four-degree dyspnea, 35 of them were intubated successfully in the first attempt after inhalation induction and 4 succeeded in the second attempt. No complications occurred in 129 JORRP children postoperatively, 17 children suffered from mild dyspnea and relieved after oxygen inhalation, 2 children were intubated and sent to intensive care unit because of postoperative hypoxemia. All JORRP children got through the peri-operative period safely. The quality of pronunciation in 101 children improved markedly and 35 suffered from slight hoarseness on the 1st postoperative day. Three children had the tracheal tube of tracheostomy removed after receiving five, four and three operations respectively. Nineteen children were followed up for 2 - 5 years. Among them, one child did not relapse 3 years after surgical management.One child suffered from laryngostenosis postoperatively. No death occurred. Complete preoperative preparation, rational anesthesia methods, careful operative procedure and airway maintenance after surgery could increase the safety for children with recurrent respiratory papilloma.

Current Management of Adult HPV: From Papilloma to Cancer

Program Description: Human papilloma virus (HPV) infection is a major cause of disease. It is causal in respiratory papillomatosis and cervical cancer and is etiologically associated with cancers of the oropharynx as well as additional anogenital sites. Our knowledge of the role of HPV in these diseases is evolving and there are yet many unanswered questions. Furthermore, the epidemiology of these diseases may change with trends in increasing promiscuity and the advent of widespread HPV vaccination. Patients have often read extensively about their diagnosis on the internet and may present with incomplete/incorrect knowledge and difficult questions about disease transmission, progression, treatment and transformation. This miniseminar brings together experts that specialize in different manifestations of HPV disease: adult and pediatric clinicians that treat recurrent respiratory papilloma (RRP), a head and neck surgeon that treats oropharyngeal carcinoma and actively researches vaccines targeting HPV related malignancy, and a guest clinician from gynecology to give insights on the treatment of HPV from a different perspective. The format will focus on case presentations to highlight the specific topics selected for discussion to include: basic biology of HPV infection and oncogenesis, treatment strategies for RRP, adjuvant treatments for RRP, counseling regarding contacts of patients with HPV related disease, HPV vaccine indications, and current concepts regarding the role of HPV in oropharyngeal cancer. There will be opportunity for the audience to ask questions throughout the presentation. Educational Objectives: 1) Understand current RRP management strategies including surgical techniques, adjuvant medications and nutritional supplements. 2) Be able to counsel patients on etiology of RRP, transmission, cancer risk, and vaccination. 3) Understand how RRP fits in the spectrum of HPV-related disease.

Use of 532-nm Pulsed Potassium Titanyl Phosphate Laser and Adjuvant Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in Children

To describe the initial pediatric experience with intralesional bevacizumab (Avastin) treatment for children with severe, recurrent respiratory papilloma (RRP). Retrospective medical chart review. Tertiary care multidisciplinary aerodigestive center. Three children, aged 3 to 6 years, with severe RRP requiring more than 4 operative interventions in 1 year whose parents (or legal guardians) consented to adjuvant treatment with intralesional bevacizumab. All 3 children were treated as follows: surgical debridement with a microdebrider, pulsed potassium titanyl phosphate laser treatments, and adjuvant intralesional injections with bevacizumab (1.25 mg total). Time interval between operative interventions, Derkay severity scale for RRP, and pediatric voice-related quality of life (PVRQOL) scores. All 3 children demonstrated increased time between operative interventions. Two children had a substantial decrease in their Derkay score and improved PVRQOL scores. One child, although time between operative interventions improved, did not have any change in Derkay score and required further adjuvant therapy. Injectable bevacizumab appears to show some efficacy in prolonging the time between treatments and therefore reducing the number of treatments per year in children with severe RRP. However, before any meaningful conclusions can be drawn, further studies must be conducted in the form of head-to-head trials looking specifically at the issues of time between treatment intervals, efficacy of one adjunct over another, vocal outcomes, and whether several adjunctive treatments confer advantage over 1 treatment. In-depth and careful informed consent is mandatory for these studies so that parents are aware of the risks and benefits (known and unknown) before such individualized decisions are made.

ProEx C Stain Analysis in Recurrent Respiratory Papillomatosis

We evaluated the presence and pattern of ProEx C stain, a marker for the proliferative capacity of cells, in laryngeal tissues, including benign, malignant, and recurrent respiratory papilloma (RRP) specimens, and compared it to hematoxylin and eosin staining for the presence of dysplasia. We performed a retrospective study with chart review. A total of 26 specimens (9 benign, 7 malignant, 10 RRP) representing 21 patients were stained. ProEx C stained positive in the nuclei of laryngeal tissue, consistent with its localization in cervical cytology specimens. Seven of 9 benign and 7 of 10 RRP specimens stained positive. The benign specimens were mostly polyps. The malignant specimens were either well or moderately differentiated squamous cell carcinoma, and they stained strongly and diffusely. In benign and RRP specimens, the basal layer typically stained positive. Other areas of epithelium stained weakly in benign specimens and variably in RRP specimens. Current analysis of hematoxylin and eosin-stained RRP specimens revealed that 30% of specimens had at least moderate dysplasia and 80% exhibited viral changes (koilocytosis). ProEx C is a clean and reliable stain in laryngeal tissue, and stains positive in RRP. This study could not definitively correlate positive ProEx C staining in areas of greater dysplasia, although a trend was observed. Further studies are necessary to determine whether ProEx C can be used in triage of cases of clinically aggressive RRP for closer follow-up or frequent operative intervention.

Prevalence of Dysplasia in Juvenile-Onset Recurrent Respiratory Papillomatosis

To quantify the prevalence of dysplasia and to evaluate the impact of use of cidofovir in recurrent respiratory papilloma biopsy specimens obtained from a pediatric population. Retrospective review of patient medical records and histopathologic test results from January 1, 1998, through December 31, 2008. Children's Hospital of Wisconsin. Patients with a history of operation treated for recurrent respiratory papillomatosis. The presence or absence of dysplasia identified in a papilloma specimen and patient characteristics, such as age of initial presentation, number of operations, tobacco exposure, treatment for reflux, and use of cidofovir, were quantified. Treatment for recurrent respiratory papillomatosis was identified in 21 patients. Age at initial diagnosis ranged from 8 months to 14 years. A total of 123 recurrent respiratory papillomatosis specimens in 20 patients were identified. Dysplasia was seen in less than 1% of samples (1/123), which represents 5% of total patients. Seven patients (35%) received cidofovir treatment and none of them developed dysplasia. These data demonstrate a lack of correlation between cidofovir treatment and dysplasia, with the P value being nonsignificant (Fisher exact test, P=.4). Dysplasia is a rare event in pediatric recurrent respiratory papillomatosis, and there does not appear to be an association between the use of cidofovir and dysplastic changes.

A controlled safety study of diindolylmethane in the immature rat model

Diindolylmethane (DIM), a natural product from cruciferous vegetables, has been shown to be a dietary component that has inhibitory effects on some tumors (e.g., laryngeal papilloma). However, current evidence to support its safety is based on adult humans or mature animals. There is little to show on its safety in children. This study is designed to assess safety in the young rat model. Prospective controlled animal study. Forty rats were separated into four treatment groups of 10 rats each, based on the amount of study drug they received in their daily food: 1) immature rats fed a low dose of DIM, (0.6 mg/kg/day); 2) immature rats fed a high dose of DIM (6.0 mg/kg/day); 3) immature rats fed no DIM (control); and 4) adult rats fed a high dose of DIM (6.0 mg/kg/day). At the conclusion of the study we collected blood to compare serum chemistries and vitamin D levels, and harvested organs to observe for any gross or histological changes among the groups. Statistical methods involved one-way analysis of variance and pairwise comparisons with Tukey multiple comparison adjustment. Although our numbers do not allow for statistical significance, there was no appreciable difference in rat weights among the immature groups, nor was there appreciable difference in serum chemistries, or gross or histological examination of liver, kidney, and bone. Diindolylmethane seems to have no adverse affects on the rat even when given in doses 3x what we propose to be therapeutic. This adds evidence to the safety of this drug in the pediatric population as a treatment option for recurrent respiratory papilloma.

Transoral trans‐stomal microdebrider excision of tracheal papillomatosis

To describe a technique for surgical removal of recurrent respiratory papilloma in the distal trachea in patients with an indwelling tracheostomy tube. A transoral trans-stomal technique for removal of distal tracheal papilloma using a modified ventilating bronchoscope setup and a microdebrider with a rotatable Skimmer blade (XOMED Products, Jacksonville, Florida, USA). Surgical removal of papillomas in the distal trachea is a challenging procedure, involving potentially competing demands for visualization, instrumentation, and ventilation. Previously described methods for management of these challenging cases provide limited ability to deliver continuous oxygenation and ventilation during the procedure. The transoral trans-stomal technique overcomes these limitations in patients who have an existing tracheostomy. This technique allows for precise removal of papilloma in the distal trachea, while providing for excellent visualization and continuous oxygenation and ventilation of the patient.

Endoscopic surgery for treatment of paediatric upper airway diseases

Abstract In September 2005, the 3rd OPBG/Mayo Clinic Joint Conference was held in Rome to highlight current views in paediatric medicine. After an overview of the various pathologies, the Otolaryngology Unit of the Bambino Gesù Children's Hospital of Rome described their own experience with endoscopic surgery for the treatment of upper airway diseases between 2002 and 2004. During this period, 1500 paediatric endoscopies were performed for obstructive upper airway disease. A total of 80% of patients were under 2 years of age. The aetiological causes of upper airway obstruction most frequently cited were: foreign bodies (the most frequent reason for urgent endoscopic treatment), choanal atresia, severe laryngomalacia, laryngeal cysts, neurological lesions (vocal fold paralysis), laryngeal clefts, laryngeal haemangiomas, recurrent respiratory papilloma, tracheoesophageal fistula, tracheal granuloma and tubercular adenobronchial fistula. In all the patients, stridor disappeared following surgery. No complications, such as aspiration or supraglottic stenosis, were identified and no revision surgeries were required. Stenting was necessary in only three cases. This study described the OPBG management of paediatric airway obstruction and outcomes during a 3-year period and was the starting point for reflection on this topic.

Tracheal Papilloma with Exceptionally Longer Interval of Recurrence

A case of recurrent respiratory papilloma of the trachea was reviewed in accordance with other literature. A 66-year-old man with the chief complaint of haemoptysis was referred to our department for meticulous checkup. According to his past medical history of laser ablation for laryngeal and tracheal papilloma, recurrence of the papilloma was first suspected and confirmed by bronchoscopic biopsy. The recurrent papilloma, of about 5 mm in diameter, was located at the same endotracheal lesion, left side of the middle trachea, where the former first and second tracheal papillomas had been detected and treated with Nd-YAG laser. Under general anaesthesia with endotracheal intubation, the patient underwent bronchoscopic resection of the recurrent papilloma with KTP laser. The bronchoscopic resection was uneventful, as was the postoperative course. In this report, the clinical manifestations of and therapeutic approach for tracheal papilloma are reviewed.