幼年型复发性呼吸道乳头状瘤病不同人乳头状瘤病毒亚型感染与临床病变侵袭性的关系

目的　分析比较不同人乳头状瘤病毒（HPV）亚型感染与幼年型复发性呼吸道乳头状瘤病（juvenileonset recurrent respiratory papillomatosis,JORRP）患儿临床病变侵袭性之间的关系。方法　研究组随机纳入55例患儿,包括7例喉标本重复测定者在内共计62例喉部活检标本。对患者既往临床资料进行回顾性分析,将病程分为侵袭性与非侵袭性。采用实时荧光定量PCR技术测定62例JORRP患儿喉活检标本HPV DNA检测,特异性引物包括HPV6和HPV11。结果　98.4%（61/62）喉标本存在HPV DNA的扩增。HPV11阳性率为52.7%（29/55）,HPV6和HPV11双重感染的阳性率为36.3%（20/55）,HPV6阳性率为9.1%,仅1例未检测出。单一HPV11亚型者初次手术年龄[（2.16±1.17）岁]较双重HPV6/11亚型感染者[（3.77±3.07）岁]小（P =0.033),临床病变侵袭性较双重HPV6/11亚型感染者强（P =0.015）。将7例JORRP患儿喉标本进行HPV DNA重复测定,发现相同个体不同时间HPV亚型感染一致率为57.1%（4/7）。结论　与双重HPV6/11亚型感染者相比,单一低危型HPV11亚型感染者初次手术年龄较小,临床病变侵袭性更强;相同个体不同时间段感染HPV亚型检出率及亚型可发生改变。     

幼年型复发性呼吸道乳头状瘤病中人乳头状瘤病毒感染状态与病情变化的相关性分析

目的 本研究拟探究幼年型复发性呼吸道乳头状瘤病（juvenile-onset recurrent respiratory papillomatosis,JORRP患儿人乳头状瘤病毒（HPV）亚型与含量的长期变化情况,及其对病程的影响。方法 纳入2011年6月～2022年6月于北京同仁医院反复多次就诊、病程持续3年以上的43例JORRP患儿,收集其就诊期间的267例术中标本及留取标本时的手术时间间隔和年手术次数等临床资料,RT-PCR法检测HPV6和HPV11的DNA含量,依据临床病情特点分为缓解组（n=22）和复发组（n=21）,统计分析HPV亚型及含量的变化与病情特点变化之间的相关性。结果 13例患儿出现HPV感染转阴趋势,其中缓解组11例,复发组2例,HPV感染状态转阴与病情缓解相关（χ2=6.537,P<0.05）。缓解组HPV11型转阴10例,复发组HPV11型转阴2例,组间比较转阴率差异显著（χ2=5.224,P<0.05）。经Mc Nemar检验,缓解组HPV11的感染率降低具有统计学意义（χ2=4.08,P<0.05）。线性回归结果提示缓解组的HPV6 ...     

无呼吸道乳头状瘤儿童上呼吸道乳头状瘤病毒的检测

目的 检测儿童扁桃体和腺样体手术标本中的人乳头状瘤病毒(human papillomavirus,HPV)DNA,以了解无复发性呼吸道乳头状瘤(juvenile-onset recurrent respiratory papillomatosis,JORRP)儿童的上呼吸道HPV感染情况.方法 前瞻性研究2008年2月至2009年1月因扁桃体肥大或炎症以及腺样体肥大手术的患儿241例,均确诊为无JORRP或其他已知HPV相关疾病.共取得新鲜的扁桃体标本177个和腺样体标本195个.为验证本研究实验方法的可靠性,取同期17例喉乳头状瘤患儿的新鲜乳头状瘤标本作阳性对照.所有标本采用荧光定量聚合酶链反应法检测HPV DNA并分型.结果 17例乳头状瘤标本HPV-DNA均阳性,均为HPV6或HPV11感染.241例患儿的372个标本中,仅2例扁桃体阳性,分别为HPV6和HPV11感染.再次追问这2例患儿的个人病史和家族史,未发现有HPV感染相关疾病,扁桃体切除样本的病理检查结果均显示淋巴组织增生,无HPV感染的特征病变,也未见恶性肿瘤迹象.本组中上呼吸道HPV感染率为0.8％ (2/241).结论 无JORRP儿童的上呼吸道也存在HPV感染,仅有HPV感染可能不足以引发JORRP.     

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。     

幼年型复发性呼吸道乳头状瘤气管切开的临床研究

目的：分析幼年型复发性呼吸道乳头状瘤（JORRP）气管切开患儿的临床特征,探讨气管切开的拔管时机。方法：对31例接受气管切开术的JORRP患儿进行回顾性分析,分析JORRP的发病年龄、气管内播散的部位、疾病侵袭性、病变生长方式等临床表现。结果：31例JORRP患儿共行气管切开术32例次,3例次为手术后1个月拔除气管套管,气管内无乳头状瘤生长,其余29例次气管内均有不同程度的乳头状瘤生长;20例次拔管患儿中,拔管3个月以上者气管内未见乳头状瘤生长。结论：JORRP患儿应尽量避免气管切开,已行气管切开的患儿应及早拔管,避免乳头状瘤向气管内发展,拔管时机可选择在乳头状瘤生长较少时,可于手术结束后即刻拔除,或术后堵管24h后拔除。     

幼年型复发性呼吸道乳头状瘤病

幼年型复发性呼吸道乳头状瘤病是儿童最常见的呼吸道良性肿瘤,由人乳头状瘤病毒感染引起,尤其是HVP6和11型.HPV的高感染率与JORRP的低发生率提示患者的自身免疫在JORRP的发生发展机制中起着重要的作用.声嘶和进行性加重的呼吸困难是JORRP的主要症状,肺部浸润是导致患儿病情恶化的主要原因,其中气管切开是病变向下气...     

小儿复发性呼吸道乳头状瘤病38例临床分析

目的 :探讨小儿复发性呼吸道乳头状瘤病 (JORRP)的临床特点。方法 :回顾分折 1986年 6月～ 2 0 0 0年 6月收治的 JORRP 38例资料。结果 :平均发病年龄 2 .9岁 ,首次诊断平均年龄 3.5岁 ,平均手术 3.45次 ,术后并发喉功能障碍 8例 (2 1.0 5 % ) ,气管切开 19例 (5 0 .0 % ) ,6例气管造口有乳头状瘤传播 (31.5 8% )。结论 :JORRP是儿童最常见的喉部肿瘤 ,由于易复发 ,常需多次手术 ;手术应注意保存喉部正常组织 ;气管切开要慎重 ,以防病变局部接种和邻近器官传播     

小儿复发性呼吸道乳头状瘤病38例临床分析

目的：探讨小儿复发性呼吸道乳头状瘤病（JORRP）的临床特点,方法：回顾19986 6月－2000年6月收治的JORRP 38例资料。结果：平均发病年龄2．9岁,首次诊断平均年龄3．5岁,平均手术3．45次,术后并发叭功能障碍8例（21．05％）,气管切开19例（50．0％）,6例气管造口有乳头状瘤传播（31．58％）,结论：JORRP是儿童最常见的喉部肿瘤,由于易复发,常需多次手术：手术应注意保存喉部正常组织,气管切开要慎重,以防 病变局接种和邻近器官传播。     

儿童复发性喉乳头状瘤样病变的临床研究

目的　探讨儿童喉乳头状瘤样病变 (juvenilrecurrentlaryngealpapillomatosis,JRLP)的治疗方法及儿童复发性呼吸道乳头状瘤 (juvenileonsetrecurrentrespiratorypapillomatosis,JORRP)与小儿喉尖锐湿疣 (infantilelaryngealcondylomaacuminatum ,ILCA)的关系。方法　回顾分析 1994年 3月～ 2 0 0 2年 3月诊治的 4 4例JRLP的临床资料。结果　 4 4例中普通组织病理学诊断为ILCA 2 8例 ,JORRP 16例 ;采用斑点杂交和聚合酶链反应检测人乳头状瘤病毒阳性率达 4 2 / 4 4。JRLP患儿平均初诊时间 1 6岁 ,平均手术次数 5 3次 ,平均手术间隔期 2 4个月 ;在总共 2 33次手术中 ,各种并发症总发生率为 3 9%。目前 ,长期缓解 18例 ,正在随访的有 11例 ,失访 10例 ,死亡 5例。手术加有治疗目的的气管切开 (延长手术间隔期 )和手术加中药两种治疗方式效果较好。JORRP和ILCA存在广泛的共性。结论　深入研究JORRP和ILCA的关系具有十分重要的理论价值和临床意义。应尽量避免用气管切开术来缓解JRLP所引起的喉梗阻 ,手术加有治疗目的的气管切开术和手术加中药治疗两种治疗方式值得进一步探讨。     

儿童复发性喉乳头状瘤样病变的临床研究

目的 探讨儿童喉乳头状瘤样病变(juvenil recurrent laryngeal papillomatosis，JRLP)的治疗方法及儿童复发性呼吸道乳头状瘤(juvenile onset recurrent respiratory papillomatosis，JORRP)与小儿喉尖锐湿疣(infantile laryngeal condyloma acuminatum，ILCA)的关系。方法 回顾分析1994年3月～2002年3月诊治的44例JRLP的临床资料。结果 44例中普通组织病理学诊断为ILCA 28例，JORRP 16例；采用斑点杂交和聚合酶链反应检测人乳头状瘤病毒阳性率达42／44。JRLP患儿平均初诊时间1．6岁，平均手术次数5．3次，平均手术间隔期2．4个月；在总共233次手术中，各种并发症总发生率为3．9％。目前，长期缓解18例，正在随访的有11例，失访10例，死亡5例。手术加有治疗目的的气管切开(延长手术间隔期)和手术加中药两种治疗方式效果较好。JORRP和ILCA存在广泛的共性。结论 深入研究JORRP和ILCA的关系具有十分重要的理论价值和临床意义。应尽量避免用气管切开术来缓解JRLP所引起的喉梗阻，手术加有治疗目的的气管切开术和手术加中药治疗两种治疗方式值得进一步探讨。     

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.     

儿童咽喉乳头状瘤病毒感染的检测

目的:探讨儿童咽喉乳头状瘤(JOP)与HPV6、HPV11病毒感染及患儿免疫功能的关系。方法:用荧光定量聚合酶链反应(FQ-PCR)检测130例JOP组织病毒DNA,并对其中68例采用流式细胞仪进行细胞免疫功能指标CD3、CD4、CD8检测。结果:130例标本中HPV6和HPV11病毒的检出率为88.46%(115/130),平均拷贝值为5.68±2.65。68例患儿CD3、CD4、CD8百分平均值分别为62.73±8.63、30.54±7.05、26.08±6.93,与对照组比较,差异无统计学意义。结论:FQ-PCR方法简便、准确、特异性强、灵敏度高、定量范围宽,可测定病原体数目为101~1010的不同程度,对JOP病毒的临床诊断、治疗及疗效观察有重要指导作用。     

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.     

Laryngeal papillomatosis: clinical, histopathologic and molecular studies

The clinical course and pathology of 57 patients with laryngeal papillomatosis were reviewed. Tissues from 26 patients were analyzed for human papillomavirus (HPV) DNA by Southern blot hybridization. Histopathologic evaluation of the papillomas showed no correlation with age of onset or clinical pattern of remission and recurrence. The pathology was characterized by abnormal squamous maturation with parakeratosis, retardation of superficial cell maturation, papillomatosis, and basal hyperplasia. HPV DNA was present in all lesions, with 92% containing either HPV-6 or 11. Latent HPV DNA was detected in clinically uninvolved tissues of 11 of 14 (78.5%) patients studied. There was no correlation between HPV type, histopathology and/or clinical pattern. Despite homogeneity of pathology, the clinical expression of laryngeal HPV infection varied widely. A mechanism for the pathogenesis of laryngeal papillomatosis, based on the concept of maturational arrest, is proposed.     

累及气管幼年型复发性呼吸道乳头状瘤的手术策略

目的 探讨累及气管支气管的复杂幼年型复发性呼吸道乳头状瘤(juvenile on-set recurrent respiratory papillomatosis,JORRP)手术策略,以降低手术风险,减少并发症.方法 选取2006年1月至2009年2月间在北京同仁医院进行手术治疗,病变累及气管内的24例JORRP患儿,共行149次手术,手术均采用全麻,术中高频喷射呼吸机支持呼吸,支撑喉镜下使用气管内镜及喉电动切割钻治疗,应用辅助通气,切除肿瘤和清除气道内出血交替.结果 患儿年龄3～16岁(中位数6岁);首次发病年龄8个月～10岁(中位数1.5岁);有气管切开病史20例,患儿气管切开年龄1～4岁(中位数2岁);术前2度呼吸困难147例次,3度呼吸困难1例次,4度呼吸困难1例次.全部患儿均接受多次手术.所有患儿术后呼吸困难均完全缓解,无死亡病例.2例次术后因高碳酸血症再次插管,1例次因术前低氧血症、高碳酸血症,术后拔管人重症监护病房1日.结论 应用高频喷射呼吸机支持呼吸,支撑喉镜下使用气管内镜及电动切割钻治疗累及气管内的青少年型复发性呼吸道乳头状瘤,在间断无通气情况下切除气管内肿瘤的策略是安全有效的.     

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.     

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.     

Severity of juvenile onset recurrent respiratory papillomatosis is not associated with socioeconomic status in a setting of universal health care

BACKGROUND: Juvenile onset recurrent respiratory papillomatosis (JORRP) results from HPV transmission. Cervical cancer, also transmitted via HPV, is known to be correlated with socioeconomic status (SES). This study aims to determine if an association exists between SES and severity of JORRP. METHODS: Cross-sectional study of all active JORRP patients at the Hospital for Sick Children in Toronto in 2005. SES information from Hollingshead surveys, Postal walk Census data, and Low Income Cutoff Data were compared with Derkay-Wiatrak disease severity scores, peak annual surgical frequency, and age of diagnosis. Statistical analysis was performed using Spearman, Mann-Whitney, and linear regression analyses. RESULTS: Twenty-one patients were surveyed. Hollingshead results were as follows: two patients (10%) were class I (major business and professional); 11 patients (52%) were class II (medium business, minor professional, technical); 4 patients (19%) were class III (skilled craftsmen, clerical, sales workers); 4 patients (19%) were class IV (machine operators, semiskilled workers); 0% were from class V (unskilled laborers, menial service workers). Interestingly, based on postal code data nine patients (45%) were below the low income cutoff as compared to the Toronto (metropolitan) and Ontario (provincial) rates of low income (17% and 14%, respectively). There was significant correlation between each of the SES measures and between disease severity measures. However, analysis of the SES measures versus disease severity measures did not demonstrate any significant relationship. CONCLUSIONS: Though almost half the patients lived below the low income cutoff, this study did not demonstrate a significant correlation between socioeconomic status and severity of disease in JORRP. One possible explanation is that universal access to the Canadian health care system is able to provide support despite a large proportion of patients being socioeconomically vulnerable. A national level study is underway to further detect any relationship between SES and JORRP severity in the general population.     

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.