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.     

Human papillomavirus DNA presence of the upper respiratory tract mucosa of healthy children

The papillomaviruses are a group of small DNA (8 kbp) viruses which induce papillomas in human and animals. Most of them can also transform epithelial cells of human and other vertebrates. Examinations of children with Recurrent Respiratory Papillomatosis (RRP), using PCR method with specific primers, revealed HPV type 6 or/and 11 in 98%-100% tissue samples. Little is known about HPV infection in upper respiratory tract of healthy children. The group of 201 healthy children (from 3 to 10 years old) was laryngologically examined. The smears from noses and throats were studied for the presence of HPV viruses DNA. PCR was performed as described by Tucker et al. 28.8% of children from the study group were HPV positive. The presence of HPV in respiratory tract in children is relatively high. "High risk" HPV are not observed in the respiratory tract in children. The Human Papillomavirus in children may be transmitted by direct contacts.     

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.

     

HPV types causing juvenile recurrent laryngeal papillomatosis in South Africa

Objectives

To identify human papillomavirus (HPV) types associated with juvenile onset recurrent laryngeal papillomatosis (RLP) in southern Africa, to determine if there is a correlation between HPV type and disease aggressiveness and to determine the diagnostic and prognostic value of rapid molecular techniques for detection and typing of HPV using laryngeal biopsies.

Methods

Laryngeal biopsies from patients undergoing surgery for RLP were screened for HPV using conventional and real-time PCR techniques. Amplicons were sequenced to determine the HPV type involved. Clinical features were correlated with HPV type.

Results

HPV was identified in papillomata from 18 out of 19 patients. Only HPV-6 and HPV-11 were identified, with no co-infections. There was 100% concordance between conventional and real-time PCR techniques. Patients with HPV-11 disease required more procedures and tended to have higher Derkay scores than those with HPV-6 disease. The HPV types identified in our patients were genetically similar to HPV types from geographically distinct regions.

Conclusions

RLP in our patient population appears to be exclusively due to HPV-6 or HPV-11. HPV-11 disease appears to be more aggressive than HPV-6 disease. Identification of the HPV types provides motivation for inclusion of vaccines against these types in vaccination programs to protect women against infection and subsequently reduce the incidence of RLP.     

The impact of cidofovir treatment on viral loads in adult recurrent respiratory papillomatosis

Cidofovir is an antiviral agent used in the therapy of recurrent respiratory papillomatosis (RRP). In this study, we hypothesized that cidofovir is effective in decreasing the viral load of human papillomavirus (HPV). We established a type specific real-time PCR and measured HPV DNA loads. The course of viral load of HPV types 6 and 11 after repeated applications of cidofovir intralesionally was compared to the clinical outcome using a modified Derkay score. In 6 of the 8 (75?%) patients, we detected HPV 6. In 2 (25?%) patients, we detected HPV 11. In all of the patients, the viral load and the modified Derkay score decreased significantly during the treatment. We conclude that viral load of HPV can be monitored using the technique described here. Cidofovir in combination with surgical debulking reduces the viral load in patients with RRP. Relapses of the symptoms cannot be avoided but might be delayed.     

呼吸道乳头状瘤HPV DNA定量检测与临床特征分析

目的探讨幼年型呼吸道乳头状瘤病(juvenile onset recurrent respiratory papillomatosis,JORRP)的临床特点及病程的相关影响因素,研究JORRP瘤体中人乳头状瘤病毒(human papillomavirus,HPV)的基因含量及其临床意义。方法收集55例JORRP患儿的临床资料,应用荧光定量聚合酶链反应(polymerase chain reaction,PCR)法检测肿瘤组织中的HPV6/11含量,并进行临床随访观察复发情况。结果JORRP发病高峰在3～4岁,2～7岁组患儿的手术间隔时间小于大于7岁以上组患儿;行气管切开术的患儿的手术次数明显多于未行气管切开手术的患儿;55例JORRP标本经荧光定量PCR检测后35例(63.6%)为HPV6/11型阳性,其DNA中位拷贝数为2.2E 07,其拷贝数与JORRP病程无明显相关性。结论2～7岁为JORRP好发及易复发年龄段,气管切开会增加患儿手术次数与风险,JORRP患儿的病程变化与HPV6/11 DNA含量无明显相关。     

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.     

人乳头瘤病毒型别与儿童复发性呼吸道乳头状瘤临床病程的相关性

目的　研究人乳头瘤状病毒（human papilloma virus,HPV）型别对儿童复发性呼吸道乳头瘤（juvenile onset recurrent respiratory papillomatosis,JORRP）临床病程的影响。方法　收集38例JORRP患儿新鲜瘤体标本,采用流式荧光杂交法检测HPV型别。将患儿分为HPV6阳性组和HPV11阳性组。量化评分其201例手术,对发病年龄、并发症、临床症状、手术次数、乳头瘤侵袭范围程度等方面进行统计学分析。结果　55.2%（21/38）JORRP患儿感染HPV6,36.8%（14/38）感染HPV11,7.9%（3/38）HPV6/11均阴性。两组患儿在发病年龄、术前临床症状评分、乳头瘤解剖亚区数、Derkay、Dikkers评分方面均有统计学差异。结论　感染HPV11发病年龄更小,侵犯范围更广病灶性状更严重,临床症状更严重,致JORRP临床病程更严重。     

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.     

Use of interferon-alpha in recurrent respiratory papillomatosis: 20-year follow-up

OBJECTIVES: The aim of this study was analysis of the results of use of interferon-alpha (IFN-alpha) in patients with recurrent respiratory papillomatosis (RRP) and correlation of the results with human papillomavirus (HPV) type. METHODS: A multicenter prospective series (42 patients from 22 hospitals) yielded 20 years of follow-up of patients with RRP and HPV typing who were treated with IFN-alpha in doses of 3 MU/m2 3 times per week. RESULTS: During long-term follow-up (mean +/- SD, 172 +/- 36.8 months), the rate of event-free survival evaluated by Kaplan-Meier analysis was 42.8%, and the overall survival rate was 82.6%. The HPV typing revealed an association of HPV 11 with a more aggressive disease course (64% of HPV 11 patients versus 24% of HPV 6 patients), a lower incidence of long-term response to IFN-alpha therapy (14% of HPV 11 patients versus 64% of HPV 6 patients), and a higher incidence of malignant transformation and mortality during follow-up (36% and 24%, respectively, of HPV 11 patients versus 0% of HPV 6 patients). CONCLUSIONS: The obtained results revealed maximal effectiveness of IFN-alpha therapy in RRP patients with HPV 6 as compared with HPV 11. The association of HPV 11 with a worse long-term response to IFN-alpha therapy and a higher incidence of malignant transformation and mortality is clinically important and indicates the necessity of HPV typing in RRP patients after the first biopsy.     

Mucosal swabs detect HPV in laryngeal papillomatosis patients but not family members

Seven patients, aged 2-7 years, with active recurrent respiratory papillomatosis (RRP) attending the University of Michigan Pediatric Otolaryngology Clinic were studied to determine if human papillomavirus (HPV) is harbored in sites of the upper aerodigestive tract other than in the laryngeal papilloma itself. We also determined if close family members had detectable virus in their oral cavities. Noninvasive swabs of buccal mucosa, posterior pharynx, nasal vestibule, and tonsillar pillar of patients, as well as buccal mucosa and posterior pharyngeal swabs of family members were studied. Swabs of the patients' papillomas served as the positive controls. HPV was detected using polymerase chain reaction (PCR) amplification and Southern hybridization techniques. Six of seven patients had detectable HPV in papilloma and endolaryngeal swabs. Four were HPV type 6, and two were HPV type 11. The patient whose swab was negative for HPV was found to be biopsy negative for papilloma 3 weeks after a single laser excision which was performed 6 months prior to the endolaryngeal swab. HPV types 16, 18 and 31 were not found in any of the patients. No swabs from other sites in patients or family members were HPV positive despite the presence of adequate DNA in the swabbed material for successful amplification of beta-actin sequences. The absence of HPV (other than in the papilloma itself) in the upper aerodigestive tract of patients and caregivers is consistent with the absence of reported cases of horizontal transmission to siblings or other family members. The findings are also consistent with the conventional view that juvenile respiratory HPV is transmitted vertically from vaginal condylomas in the mother.     

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.     

婴幼儿呼吸道乳头瘤病人乳头瘤病毒的检测

目的：研究人乳头瘤病毒（ＨＰＶ）与婴幼儿呼吸道乳头瘤病临床病理特征之间的关系。方法应聚合酶链式反应－限制性片段长度多态性技术，对１３例婴幼儿呼吸道乳头瘤病组织中的ＨＰＶ进行定型分析。结果：ＨＰＶ阳性率为１００％，其中ＨＰＶ６占６１．５％（８／１３），ＨＰＶ１１占３０．８％（４／１３），ＨＰＶ１５占７．７％（１／１３）。无一例ＨＰＶ１６、３１、３３、５２、５８阳性。每例患者多次手术标本检测结果一致。     

Presence of human papillomavirus DNA in tonsillectomy specimens

OBJECTIVES: The objectives of this prospective case-control study were to study the prevalence of human papillomavirus (HPV) in tonsillectomy specimens from pediatric patients without recurrent respiratory papillomatosis (RRP), and to study methods of HPV detection. METHODS: Fifty pediatric patients without known RRP undergoing tonsillectomy for hypertrophy or recurrent tonsillitis were enrolled in the study. After tonsillectomy, a 20-mg section was subjected to DNA extraction, and DNA content and purity were confirmed with spectrophotometry. Polymerase chain reaction (PCR) was performed using consensus primer pools PGMY 09/11 targeted at the L1 region. Amplification products were detected and analyzed with standard agarose gel electrophoresis. Positive samples were then subjected to reverse line blot assay to determine virus genotype. Laryngeal papilloma specimens of 15 patients obtained during routine debulking procedures were also analyzed and served as positive controls. RESULTS: Of 50 tonsil samples tested, two were positive for HPV DNA after PCR and gel electrophoresis. One of these samples was confirmed with typing and tested positive for HPV 11. All 15 papilloma specimens were positive for DNA of HPV types 6 and/or 11. CONCLUSIONS: In the current study, the prevalence of HPV DNA in tonsillar tissue of patients without RRP is 2%, whereas the incidence of this disease is 2 to 4 cases per 100,000 (0.004%). These findings are significantly different (P = .005 within a 95% confidence interval) suggesting that host factors in addition to infection play a role in pathogenesis of RRP. The molecular methods described in this study are well suited for detection of HPV in tonsillar tissue.     

General primer-mediated polymerase chain reaction for simultaneous detection and typing of human papillomavirus DNA in laryngeal squamous cell carcinomas

The aim of this study was to investigate the prevalence of different human papillomavirus (HPV) types in laryngeal squamous cell carcinomas using general primer-mediated polymerase chain reaction (PCR). Tumour sections from 42 patients with laryngeal carcinomas were investigated. For HPV DNA amplification, consensus primers were used which were directed to the LI coding region of the HPV genome. Analysis of the PCR products was done using 2% agarose gel electrophoresis followed by restriction enzyme analysis to identify different HPV types. Amplification of the human TGF-β DNA was successfully performed in 36/42 (85.7%) of samples confirming the presence of sufficient DNA for viral amplification. HPV DNA was detected in 8/36 (22.2%) of the tumours examined (three HPV-6, two HPV-16, one HPV-11, two unknown HPV types). HPV DNA was not detected in any of the non-neoplastic laryngeal mucosa which was used as control (n = 15). Fifty per cent of women had HPV-positive tumours compared with 8% of men (x²= 5.8, P<0.05). Our data indicate that while the overall prevalence of HPV in laryngeal carcinomas is fairly high (22.2%), the frequency of high-risk types (HPV-16 & HPV-18) is low (5.5%). HPV probably acts as a promoter in the multistep process of carcinogenesis in squamous mucosal cells of the larynx.     

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.     

复发性呼吸道乳头状瘤病

本文结合一组63例复发性乳头状瘤的基础及临床研究资料进行分析，其中16例的瘤组织以Slotblot和Southernblot杂交技术检测HPV－DNA，其阳性率：HPV6b为87.5％，HPV11为93．7％，HPV16为81．2％。本文就病因学、感染途径、复发部位与上皮组织特性及治疗选择进行讨论。     

Laryngeal verrucous carcinoma: A clinicopathologic study and detection of human papillomavirus using polymerase chain reaction

Laryngeal verrucous carcinoma (LVC) is a rare, well-differentiated variant of squamous carcinoma with a low malignant potential. Human papillomavirus (HPV)–16 DNA has been identified in a small number of LVC and an etiologic relationship has been suggested. A correlative clinical and molecular pathological study was performed in order to determine the prevalence and typing of HPV DNA in LVC. Possible associations between patient and tumor subsets, and the presence of HPV DNA were also investigated. Formalin-fixed, paraffin-embedded tissue samples from 29 patients with LVC were examined by polymerase chain reaction (PCR) using DNA primers specific for HPV types 6b/11, 16, and 18. Overall, HPVDNA was detected in 13 (45%) of the cases. Of these, HPV-16 DNA, HPV-18 DNA, and both HPV-16 DNA and HPV-18 DNA were detected in 4 (14% overall; 31% of positive cases), 4, and 5 (17% overall; 38% of positive cases), respectively. HPV-6b/11 DNA was not detected in any LVCs. In 16 cases, no HPV DNA was detected. There was a trend toward HPV DNA detection in higher stage tumors. HPV DNA detection was unrelated to patient age, tumor site, or radiotherapeutic responsiveness. The detection of HPV DNA in 45% of LVCs suggests an association between the presence of HPV-16 DNA and HPV-18 DNA, and some LVCs.