Prognostic factors of recurrent respiratory papillomatosis from a registry of 72 patients

Conclusions: The database revealed severity factors relating to human papillomavirus (HPV) type and age at diagnosis. While not exhaustive, the database is easy to use and could serve for a European multicentre epidemiological study. Objectives: To propose a database as a starting point for a national registry and to estimate prognostic factors in recurrent respiratory papillomatosis (RRP). Materials and methods: This was a retrospective study carried out in a tertiary care teaching hospital. From January 2005 to July 2007, epidemiological, clinical and treatment information on patients undergoing endoscopy for RRP in the department was entered in a database. Data were collected on three forms: the first comprised information about disease history before assessment in the department, the second about the disease and its treatment in the department, and the third about evolution after treatment. Results: Data on 72 patients were entered into an RRP database between January 2005 and July 2007. In all, 82% had already been treated for RRP in a different centre; 24 had juvenile-onset (JORRP) and 48 adult-onset (AORRP) papillomatosis. Cidovir injections had been administered to 91% of the patients. Histology found nine cases of dysplasia, one of carcinoma in situ and one of invasive carcinoma. Subglottic and tracheal locations were significantly more frequent in JORRP than in AORRP, as were the maximum Derkay scores and annual numbers of endoscopies. Patients with type 11 HPV had significantly more endoscopies per year than those with type 6.     

Human papilloma virus vaccination in patients with an aggressive course of recurrent respiratory papillomatosis

In the case of an aggressive course of recurrent respiratory papillomatosis (RRP), adjuvant therapy can be used besides surgery. The aim of the study was to investigate the influence of vaccination with a quadrivalent vaccine against human papilloma viruses (HPV) types 6, 11, 16 and 18 on the course of RRP. Eleven subjects aged 13–46 years with a rapid growth of laryngeal papillomas were included in the study. They were vaccinated with three doses of the quadrivalent prophylactic HPV vaccine (Silgard^®, MSD) and followed up for 12–52 months. The intervals between the successive surgical procedures, the extension of the disease (Derkay score) at each surgery, and the number of surgical procedures per year before vaccination and after its completion were compared. The mean interval between the surgical procedures was 271.2 days before the vaccination and 537.4 days after it (p = 0.034). The mean number of surgeries per year was 2.16 before the vaccination and 0.93 after it (p = 0.022). The Derkay score did not change significantly after vaccination. Complete remission of the disease was observed in one patient, partial response to the vaccination was observed in seven patients and no response was observed in three patients. In conclusion, vaccination with the quadrivalent HPV vaccine can favorably influence the course of RRP in patients with the rapid growth of the papillomas. It significantly prolongs the intervals between the surgical procedures and reduces the number of procedures needed in the majority of patients. The present investigation can serve as a pilot study for further research. For a final conclusion a longer follow-up and studies on more patients are necessary.     

Current diagnostic and management trends for recurrent respiratory papillomatosis

PURPOSE OF REVIEW: The purpose of this review is to discuss recent literature regarding diagnostic and management trends for recurrent respiratory papillomatosis (RRP) published within the past year. This includes a discussion of new information regarding the epidemiology and pathogenesis of RRP and an update on adjuvant therapy and new surgical techniques. RECENT FINDINGS: Epidemiological studies have confirmed that juvenile-onset RRP is the most common and most aggressive form of the disease. Age at diagnosis is the most important determinant of disease severity, with younger patients requiring significantly more annual surgeries and more likely to have multicentric disease. Distal tracheal or pulmonary RRP is rare, but carries a significant increase in morbidity and mortality. Research into the pathogenesis of RRP has focused on the genetics of HPV infection and host-virus interactions, suggesting a genetic basis for host susceptibility to RRP. At the present time, surgery remains the mainstay of treatment for RRP. However, recurrence after surgery is common and the search for effective adjuvant therapies is ongoing. The antiviral drug cidofovir has demonstrated efficacy against RRP and is considered a promising new adjuvant treatment of this disease. In an attempt to minimize the untoward effects of surgery, the pulsed-dye laser (PDL) has emerged as a safe and efficacious treatment for select patients with RRP. SUMMARY: While a cure for RRP remains elusive, there has been substantial progress in the diagnosis and management of this disease. Significant advances in clinical and basic science research have dramatically improved our understanding of the epidemiology and pathogenesis of the disease and led to the development of promising new adjuvant therapies and surgical techniques. This has translated to an improved quality of life for many patients with RRP.     

Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP Task Force.

OBJECTIVE: To characterize the spectrum of juvenile-onset recurrent respiratory papillomatosis (RRP) in the United States and to obtain data about the natural course of the disease and its response to treatment. SETTING: Twenty tertiary-care pediatric otolaryngology centers throughout the United States. PATIENTS: All patients with active RRP aged less than 18 years at the participating sites. MAIN OUTCOME MEASURES: Number of surgical procedures performed per year, progression of papillomas to previously nondiseased anatomical sites, drug interventions and other adjuvant therapy, and need for tracheostomy. RESULTS: Data were collected from 399 children enrolled from January, 1, 1997, through December 31, 1998. There were 51.9% male; 62.7% white, 28.3% black, 9.0% other or unknown racial group; 10.8% Hispanic ethnicity. Mean age at diagnosis was 3.8 years (range, 0.1-16.3 years) and mean duration of disease was 4.4 years (range, 0.03-18.9 years). The mean number of surgical procedures per child was 4.4 per year (range, 0.2-19.3 per year). Children whose RRP was diagnosed at younger ages (<3.0 years) were 3.6 times more likely to have more than 4 surgical procedures per year (P=.001) and almost 2 times more likely to have 2 or more anatomical sites affected (P=.008) than were children whose RRP was diagnosed at later ages (> or =3.0 years), after adjusting for sex, race, and years of treatment. CONCLUSIONS: Children whose disease was diagnosed before age 3 years were more likely than children aged 3 years or older to have more severe disease as measured by the mean number of surgical procedures performed and by the number of anatomical sites affected. The registry will form the basis for future analysis on the outcome of disease, natural course of RRP under management strategies, prevention strategies, and public health importance.     

Safety of paediatric day-stay laryngeal surgery for recurrent respiratory papillomatosis

ObjectivesSafety assessment of day-stay laryngeal surgery in a cohort of children with recurrent respiratory papillomatosis (RRP). Recurrent respiratory papillomatosis is a chronic debilitating disease which usually requires multiple recurrent interventions under general anaesthesia. Day-stay surgery is an attractive option as it allows avoiding the inconvenience and costs of routine overnight admissions while recovering in the safe environment of the family home. This is the first study to assess the safety of day-stay laryngeal surgery in this cohort of patients.MethodsRetrospective cohort study of all consecutive RRP procedures performed between December 1998 and May 2015 in a single paediatric tertiary-level hospital.ResultsA total of 465 surgical procedures were performed in 20 patients. Average age on diagnosis was 4.5 years. 415 (89.25%) of the procedures were done as day cases without overnight admission. Average number of procedures per patient was 20 and 25 for Children positive to HPV6 and HPV11, respectively. Only one patient after one single procedure (presenting 0.21% of total procedures, 0.24% of day-stay procedures) represented after discharge.ConclusionsDay-stay surgery for children with RRP has a favourable safety profile in selected cases.     

Prevalence of human papilloma virus types and their influence on the course of the disease in children suffering from recurrent respiratory papillomatosis

The type of human papilloma virus (HPV) was determined in 26 children aged between 1 year 10 months to 15 years 5 months suffering from recurrent respiratory papillomatosis (RRP). Polymerase chain reaction identified DNA of HPV type 6, 11, 16 and 18. HPV DNA was detected in all the patients including fifteen patients infected with HPV type 11; seven patients infected with HPV type 6; four children infected with HPV type 6 and 11. Types 16 and 18 of HPV were not detected. The analysis of RRP course has found that laryngeal papillomatosis runs a more aggressive course in cases with HPV type 11 infection than in those with HPV type 6.     

Efficacy of microsurgery in combined with topical-PDT in treating recurrent respiratory papillomatosis: compare JORRP with AORRP

Abstract

Background: Recurrent respiratory papillomatosis (RRP) remains a challenging and frustrating disease to treat.

Objective: To explore the efficacy of microsurgery in combined with Topical-PDT in treating recurrent respiratory papillomatosis.

Materials and methods: Fifty patients with RRP were treated with microsurgery in combined with Topical-PDT. Medical document of each patient was retrospectively reviewed. Detailed clinical information, metrics of clinical course, and current results were evaluated.

Results: Juvenile onset RRP (JORRP) might experience a more aggressive course than AORRP (adult onset RRP) with higher Derkay score (p?<?.01) and higher operation frequency per year (p?<?.01). Microsurgical excision combined with Topical-PDT every 25?days achieved “remission” of disease in 78% of patients, “clearance” of disease in 52%, and “Cured” in two patients. Each patient who achieved “remission” of disease, performed 6.82?±?3.39 operations, and continued 8.93?±?7.03?months of treatment duration. No statistically differences were found in these two aspects between JORRP and AORRP. A negative correlation between tracheotomy and the efficacy of microsurgery in combined with Topical-PDT was found (p?=?.025, Pearson’s r = –0.3).

Conclusions and significance: Microsurgery in combined with Topical-PDT might be a powerful method to treat RRP. Tracheotomy is a negative factor for this therapy.     

Children and partners of patients with recurrent respiratory papillomatosis have no evidence of the disease during long-term observation

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract. The aim of our study was to investigate whether children and partners of patients with RRP develop the same disease and to determine whether there is an impact of pregnancy on the course of RRP. PATIENTS AND METHODS: Thirty-eight of 42 patients with RRP were accepted for a multicenter prospective study in Germany in 21.06.83-12.03.90. Mean follow-up duration was 15.3+/-1.8 years. The data of partners of patients with RRP was collected during the period of observation and then updated via interviews in January 2006. Twenty-nine children and four grandchildren were born to 14 patients with RRP. Fifteen of 448 cases of patients with RRP were treated in Saint Vladimir Moscow Children's Hospital in Russia in 1988-2003 and analyzed retrospectively. Sixteen children and one grandchild were born to 15 patients with RRP from Russia. In both studies, the virus type of patients with RRP was identified by nested PCR or Southern blot hybridization. Statistical analysis was performed using Fisher's exact test (probability value set at p<0.05). RESULTS: All children born to patients with RRP were healthy. RRP was not diagnosed in any of them on the basis of clinical or histological examination. Four of 45 children developed dysphonia, two of them had vocal cord nodules. None of the sexual partners of patients has developed RRP during the follow-up period. Pregnancy was accompanied by excessive growth of papillomas in all women (100%) with RRP associated with HPV type 11, and only in 16.7% of women with RRP associated with HPV type 6 (p=0.001). CONCLUSIONS: Patients with RRP are able to have healthy children regardless of the stage of the disease. Partners of RRP patients do not develop RRP during an observation period of 15 years. Pregnancy has a negative impact on the course of RRP and local laryngeal status in patients; it is more significant in HPV type 11 associated cases as it is manifested by more rapid papillomas growth and more frequent recurrence.     

Extraesophageal acid reflux and recurrent respiratory papilloma in children

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is a benign infectious disease which is caused by the human papilloma virus (HPV). When it infects the larynx, hoarseness and airway obstruction are often the presenting symptoms. Latent virus is found in the laryngeal mucosa of many more patients than exhibit the disease. The factors which lead to virus activation have not been identified, however, extra-esophageal acid reflux disease (EERD) has been suggested as one of these factors. METHODS: This is a case series of four patients with RRP who had increase in severity of their disease with the recognition of concurrent extra-esophageal acid reflux. The clinical course of the papillomatosis and the diagnosis and treatment of reflux are compared over time. RESULTS: In all four cases, with identification and treatment of the EERD, control of the RRP improved, and in at least two patients, was complete with resolution of the EERD. Lapses in compliance with medications or behavioral and dietary recommendations in three out of four patients led to a rebound in symptoms and signs of RRP, including worsening of vocal quality and the endoscopic appearance of the larynx. CONCLUSION: The clinical course of these patients suggests a link between the presence of EERD and RRP. The inflammation induced by chronic acid exposure may result in the expression of HPV in susceptible tissues. Prompt diagnosis and effective treatment of EERD should be considered in all patients with difficult to control RRP or with clinical presentation or endoscopic signs of EERD.     

Effect of human papilloma virus expression on clinical course of laryngeal papilloma

Conclusion. Our observations suggest that human papilloma virus (HPV) 6/11 is the main causative agent of laryngeal papilloma and that detection of active HPV DNA expression may be helpful in identifying patients with aggressive recurrent laryngeal papilloma. Objectives. HPV is assumed to be the main causative agent of this disease. We investigated the expression of the entire genotype of HPV in cases of laryngeal papilloma and correlated their expression with the clinical course of the disease. Subjects and methods. Seventy cases of laryngeal papilloma were evaluated for the presence of the HPV genome by in situ hybridization (ISH) using wide-spectrum HPV DNA probe. Specific types of HPV infection were determined by DNA ISH using type-specific HPV DNA probes (HPV 6, 11, 16, 18, 31, 33). Separate analyses were conducted comparing viral types, frequency of recurrences and duration of disease-free periods. Results. We detected HPV DNA in 40 of the 70 laryngeal papilloma cases (57%). In particular, HPV DNA was detected in 75% of the juvenile types. There were significant associations between HPV and laryngeal papilloma (p<0.01). Among the HPV-positive cases, major specific types were HPV 6/11 (97%). Significant associations were also noted between viral expression and clinical course.     

Identification of HPV DNA in patients with juvenile-onset recurrent respiratory papillomatosis using SYBR Green real-time PCR

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract in children. Human papillomavirus (HPV) has been implicated as the cause of RRP, most commonly types 6 and 11. The present study was undertaken to evaluate the occurrence of HPV types in a group of patients with juvenile-onset RRP (JORRP). METHODS: The study group consists of 23 patients with JORRP. The clinical records of the patients were reviewed, and JORRP was classified as non-aggressive or aggressive. The laryngeal biopsies were taken and investigated for HPV DNA presence using real-time polymerase chain reaction (PCR) with a set of consensus primers (MY09/11). Viral typing was subsequently performed by real-time PCR with type-specific primers for HPV types 6, 11, 16, 18, 31, and 33. RESULTS: HPV presence was detected in all samples with amplifiable DNA. HPV-11 was revealed in 61.9% of the patients and HPV-6 in 23.8%. Double positivity for HPV types 6 and 11 was identified in 14.3%. Our findings suggest that RRP runs a more aggressive clinical course when HPV-11 infection is present (p=0.0265). CONCLUSIONS: Our results suggest a high frequency of HPV infection in the upper respiratory tract of the studied patients. We believe that the routine application of molecular techniques such as PCR for detection and analysis of HPVs in patients with RRP has diagnostic and prognostic significance.     

Molecular transformation of recurrent respiratory papillomatosis: viral typing and p53 overexpression

Recurrent respiratory papillomatosis (RRP) is a histologically benign disease of the larynx, trachea, and bronchi. Here we report on the histologic and molecular characteristics of 7 cases of malignant transformation of RRP to squamous cell carcinoma (SCCA). The clinical histories of 7 patients with RRP who developed SCCA were carefully reviewed. Sequential biopsies were available from 5 of the 7 cases of spontaneous transformation of RRP to SCCA and were reviewed. In addition, p53 protein overexpression and human papillomavirus (HPV) typing for all cases was examined. The average age of patients with juvenile-onset RRP was 3 years, and that of patients with adult-onset RRP was 31 years. The average age of onset of transformation to SCCA was 28 years. All patients had laryngeal involvement with RRP, and 3 of the 7 patients had tracheal extension of disease. Five patients were tracheotomy-dependent. Four of the 7 patients developed SCCA of the lung, while 3 patients developed laryngeal SCCA. There was no consistent histologic progression from squamous papilloma to papilloma with dysplasia, and all but 1 of the SCCAs were well differentiated. The overexpression of p53 protein was variable in each of the 5 patients. We detected HPV types 6/11 in papillomas from 3 patients, and HPV types 6/11, 16/18, and 31/33/51 in a papilloma of a fourth patient. No HPV DNA was detected in papillomas of 2 patients. We found HPV 6/11 in 4 of the carcinomas. We conclude that the spontaneous transformation of RRP to SCCA is not characterized by a histologic progression through dysplasia over time. Transformation can result in the loss of HPV expression. It does not appear that p53 is a molecular marker for monitoring the transformation process. Thus, these cancers may be very difficult to diagnose histologically and clinically early in the course of the transformation of the disease.     

Prevalence and clinical implications of low-risk human papillomavirus among patients with recurrent respiratory papillomatosis in Rio de Janeiro,Brazil

ObjectiveThe aim of this study was to investigate the presence of human papillomavirus (HPV) in biopsy specimens from juvenile and adult patients with histopathological diagnosis of recurrent respiratory papillomatosis (RRP) treated in two public hospitals in Rio de Janeiro, Brazil.MethodsWe performed the detection and genotyping of HPV by PCR technique for the types 6, 11, 16, and 18 in biopsy specimens from 41 RRP patients.ResultsThe juvenile onset RRP (JoRRP) corresponded to 61% and the adult onset RRP (AoRRP) corresponded to 39% of the study group. Prevalence of males was observed in both the adult (81.3%) and the juvenile (56%) groups. Lesions in the larynx were more frequent in the glottis (46%). Genotyping analysis only revealed patients with HPV-6 (34.1%), HPV-11(17.1%), and co-infection HPV-6 and -11 (48.8%). RRP severity was significantly associated with the JoRRP (p < 0.001), with extralaryngeal disease and more surgeries. However, no significant association between RRP severity and HPV types was found. One co-infected patient in the JoRRP died due to the evolution of the disease with lung involvement.ConclusionThese results show the strong association of HPV-6 and/or HPV-11 types with RRP and could complement the diagnosis, prognosis, and therapies for these patients. In addition, the HPV vaccination should be encouraged to prevent the disease.     

Risk factors for aggressive recurrent respiratory papillomatosis in Chinese juvenile patients

Abstract

Background: Aggressive juvenile-onset recurrent respiratory papillomatosis (JORRP) threatens patient lives if not receives immediate surgical intervene. Even with surgical intervene, complete remission of this disease is not approachable. Therefore, understanding the factors relevant to disease severity and prognosis will do help to the treatment strategy and health management of this disease.

Objective: This study aimed to explore the clinic, laboratory and socioeconomic characteristics of patients and evaluate the risk factors for aggressive JORRP.

Methods: The information of clinical and socioeconomic status of the patients was reviewed and its association with disease severity was analyzed. Papilloma from JORRP patients undergone surgeries was used to determine HPV subtypes by real-time PCR. The profiles of mRNA expression in the papilloma were assessed using microarray.

Results: Age at diagnosis and socioeconomic status were shown to associate with the severity of JORRP. There was no differential severity considering different HPV subtype. The mRNA expression of nucleotide binding oligomerization domain receptor protein 3 (NLRP3) and Gasdermin B (GSDMB) was reduced in papillomas.

Conclusions: A younger age at diagnosis and low socioeconomic status were associated with the severity of JORRP. mRNA expression of NLRP3 and GSDMB in the papillomas of JORRP patients was significantly reduced.

• Abbreviation: JORRP: Juvenile-onset recurrent respiratory papillomatosis; RRP: Recurrent respiratory papillomatosis; OSAS: Obstructive sleep apnea syndrome; NLRP3: Nucleotide binding oligomerization domain receptor protein 3; GSDMB: Gasdermin B.

     

A 585-nanometer pulsed dye laser treatment of laryngeal papillomas: Preliminary report

Objectives/Hypothesis: Standard management of recurrent respiratory papillomatosis (RRP) currently consists of CO₂ laser microsurgical ablation of papillomas. Because of the recurrent nature of this viral disease, patients are often faced with significant cumulative risk of soft tissue complications. As a minimally traumatic alternative to management of RRP, we have investigated the use of the 585-nm pulsed dye laser (PDL) to cause regression of papillomas by selective eradication of the tumor microvasculature. Study Design: Nonrandomized prospective pilot study. Methods: Patients with laryngeal papillomas were treated with the PDL at fluences of 6 J/cm ² (double pulses per irradiated site), 8 J/cm ² (single pulses), and 10 J/cm ² (single pulses), at noncritical areas within the larynx, using a specially designed micromanipulator. Lesions on the true cords were treated with the CO₂ laser, using standard methodology. Results: Clinical examination of three patients treated to date showed that PDL treatment appeared to produce complete regression of papillomas. Unlike the sites of lesions treated by the CO₂ laser, the epithelial surface at the PDL treatment sites was preserved intact. Conclusions: These preliminary results suggest the PDL may eradicate respiratory papillomas with minimal damage to normal laryngeal tissue. Further analysis of the ongoing study is required to demonstrate potential benefits of the technique.     

The role of HPV type in Recurrent Respiratory Papillomatosis

Objective

Human Papillomavirus (HPV) 6 and 11 are the aetiological agents responsible for Recurrent Respiratory Papillomatosis (RRP). There is general consensus that HPV11 results in more aggressive disease compared to HPV6.

Method

Pubmed was searched using the terms respiratory papillomatosis, HPV 6 and HPV11. Comparisons were made in the outcomes of HPV6 versus HPV11 positive RRP disease.

Results

There are numerous sub-types or variants of both HPV6 and HPV11. These sub-types have different activities at least in-vitro. The numbers of different HPV types within RRP tissue may be more extensive than initially appeared. This depends specifically upon the HPV types tested for.

Conclusion

The clinical differences between HPV6 and HPV11 disease may not be accurately predictable as these viruses exist in numerous sub-types. Also, RRP tissue may contain more than one subtype or even be co-infected with other viruses that may influence outcome. In-vitro studies upon cell lines are a reasonable starting point for evaluation of these differences.     

Nasopharyngeal papillomas treated with CO2 laser and human papillomavirus vaccination

This case report describes the use of CO2 laser and quadrivalent human papillomavirus (HPV) vaccination in two patients with nasopharyngeal HPV11‐positive recurrent respiratory papillomas (RRP). These patients initially underwent CO2 laser excision but developed recurrent lesions and underwent HPV vaccination as adjunct therapy. The recurrent lesions shrank after vaccination and were again excised with CO2 laser. Subsequently, these patients had no recurrence of lesions on long‐term follow‐up at 33 months or 6 years after surgery. Thus, in patients with nasopharyngeal RRP, resection with CO2 laser, and HPV vaccination as adjunct therapy should be considered in HPV11‐associated cases. Laryngoscope , 127:2279–2281, 2017     

Human papillomavirus and risk of laryngeal cancer

We determined the relationship between human papillomavirus (HPV) infection and the HPV types detected in 44 patients with squamous cell carcinoma, 10 laryngeal leukoplakia patients, and 12 patients evaluated for benign laryngeal conditions (controls). The sources of HPV DNA were from brushings from the upper respiratory tract and lesion (benign or malignant), oral rinses, and biopsies of patient lesions. Polymerase chain reaction (PCR) and DNA sequencing were used to identify and type HPV. We detected HPV in 25.0% (11/44) of patients with laryngeal cancer, in 30.0% (3/10) of patients with laryngeal leukoplakia, and in 16.7% (2/12) of noncancer controls. Patients with cancer were not more likely to be identified with oncogenic HPV types ( 18.2%) than either the leukoplakia group (20%) or the control group (16.7%). An increased risk of disease was associated with current tobacco use and former alcohol drinking in cancer patients versus controls and in leukoplakia patients versus controls (all p < .05). After we controlled for tobacco and alcohol effects on the risk of disease, exposure to oncogenic HPV types was associated with an increased risk of laryngeal cancer (odds ratio = 3.0) and of laryngeal leukoplakia (odds ratio = 6.0) compared to controls, although the results were not statistically significant. This study suggests that although HPV infection and HPV oncogenic types are not found at a higher frequency in laryngeal cancer or laryngeal leukoplakia as compared to controls, infection is associated with an increased risk of disease after controlling for the effects of alcohol and tobacco use.