喉乳头状瘤临床行为与细胞增殖活性关系的研究

利用ISH方法以及免疫病理手段对不同型的LP组织的标本进行PCNA、P53检测，探讨不同型HPV与LP的发生发展的相关机制，以寻求有效的检测方法帮助临床对LP的预后进行评估。标本选自1994年1月～1995年12月间我院收治的LP共36例。ISH法HPV6b／11阳性率为75％，明显高于HPV16和／或HPV18的表达。10例喉鳞癌各有1例HPV16、18阳性，无HPV6b／11阳性。ABC法行P53检测，36例LP标本中仅1例恶变组织阳性表达Ⅱ级（2．8％）；10例喉鳞癌中9例阳性表达（90．0％），其中Ⅱ级以上阳性表达6例（60．0％）。PCNA阳性表达27／36例（75％）；其中JOP组与AOP组阳性率有显著差异（P＜0．05）。本研究表明LP与HPV感染有极为密切的关系，认为HPV分型的检测在判断LP转归中有意义。PCNA阳性表达程度在预测LP肿瘤的活跃程度方面是一个很有意义的指标。P53蛋白表达在喉鳞癌与LP中有显著差异。     

人乳头状瘤病毒感染与鼻内翻性乳头状瘤的发病及恶变关系的研究

目的:探讨人乳头状瘤病毒(HPV)感染与鼻内翻性乳头状瘤(NIP)的发病及恶变的关系。方法:将57例NIP患者分为不伴恶变组(45例)和伴恶变组(12例),应用PCR技术,检测其HPV6、11、16、18等4个型别的HPV-DNA,同时以30例鼻息肉患者为对照组。结果:57例NIP患者HPV-DNA总阳性率为64.9%(37/57)。不伴恶变组HPV-DNA阳性率为60%(27/45),均为单一的低危型HPV11型感染;伴恶变组HPV-DNA阳性率为83.3%(10/12),以检出HPV16、18型DNA为主,其中5例为双重感染(4例为HPV16、18型,1例为HPV11、16型),4例为单一型HPV16型感染,1例为单一型HPV11型感染。而30例鼻息肉患者均未检出HPV-DNA。结论:HPV在NIP的发病中有重要作用,而高危型HPV16、18型与NIP恶变可能密切相关。     

人乳头状瘤病毒及pRb在头颈鳞状细胞癌中的表达

目的：探讨人乳头状瘤病毒(HPV)和视网膜母细胞瘤蛋白(pRb)在头颈鳞状细胞癌中的表达及其临床意义。方法：对首选手术治疗的73例头颈鳞状细胞癌患者，用GP5( )bioGP6( )介导的酶联吸附免疫PCR和type-specific PCR检测HPV；免疫组织化学法检测pRb在肿瘤组织中的表达。结果：HPV DNA在73例肿瘤组织中的阳性率为12．3％，均为HPV 16 DNA；口咽癌患者HPV阳性率为18．0％，口腔癌患者HPV阳性率为7．5％。pRb在73例肿瘤组织中的阴性率为12．3％。结论：尽管HPV阳性肿瘤临床多为进展期，常伴有颈淋巴结转移，但HPV阳性患者预后较阴性患者为好．提示HPV阳性、pRb阴性的头颈鳞状细胞癌对放疗反应敏感．     

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Ｓｏｌｔ ｂｌｏｔ和Ｓｏｕｔｈｅｒｎ ｂｌｏｔ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。     

婴幼儿咽喉乳头瘤组织人乳头瘤病毒感染的探讨

目的　探讨温州地区人乳头瘤病毒感染和婴幼儿咽喉乳头状瘤的关系。方法　应用聚合酶链反应和核酸斑点杂交技术检测 35例婴幼儿咽喉乳头瘤组织和 10例对照组组织 (小儿声带小结 )HPV6、11、16、18、3 3 5个型别的DNA。结果　乳头瘤组织HPV感染率为 91 4% (30 / 35 ) ,其中HPV6型检出率为 5 4 2 % (19/ 35 ) ,HPV11型感染率为 2 5 7% (9/ 35 ) ,多重型别HPV6 11感染率为 11 4% (4/ 35 ) ;HPV16、18、3 3 型 ,均为阴性。对照组各型检测结果均为阴性 ,两者对比差异有高度显著性 (P <0 0 0 1)。结论　温州地区婴幼儿咽喉乳头瘤的发生与HPV感染密切相关 ,尤以HPV6感染为主。PCR结合核酸斑点杂交技术检测HPV具有敏感性高、特异性强的优点 ,值得推广。     

人类乳头状瘤病毒与鼻息肉的关系

目的：探讨人类乳头状瘤病毒感染与鼻息肉发病的相关性。方法：取70例鼻息肉组织标本，用HPV-DNA-Typing方法进行人类乳头状瘤病毒(HPV-DNA)检测及病毒分型，24例正常鼻腔粘膜作对照。结果：70例鼻息肉中有19例(27．14％)HPV-DNA感染，24例正常鼻腔粘膜中1例感染HPV-DNA(4．17％)，HPV发现以HPV-5型为主。结论：鼻息肉发病可能与HPV感染有一定关系。     

儿童喉乳头状瘤与人乳头状瘤病毒的相关性及其免疫综合治疗

对2002～2005年收治的60例儿童喉乳头状瘤（JLP）的病变组织进行人乳头状瘤病毒（HPV）分型及体液、细胞免疫检测，并对其临床资料进行回顾性分析，以探讨JLP患儿HPV感染类型、途径及细胞、体液免疫水平，提高对其临床特点的认识，探讨有效的治疗方法。     

儿童喉乳头状瘤细胞的原代培养及生物学特性研究

目的 探讨人乳头状瘤病毒（human papilloma virus,HPV)感染阳性患儿喉乳头状瘤细胞在体外培养的生物学特性。方法 2000年3月－2001年4月采用组织块培养法培养10例12例次喉乳头状瘤患儿手术的标本－HPV感染阳性患儿喉乳头状瘤细胞，观察其生长情况，计数法绘制细胞生长曲线，运用共同引物聚合酶链反应（polymerase chain reaction,PCR)法及核酸分子斑点杂交方法对喉乳头状瘤细胞在培养前后的HPV DNA进行检测。结果 HPV感染阳性的喉乳头状瘤细胞在体外生长时间可长达6周，培养前后细胞内均含有HPV的DNA。细胞生长分为3期，延缓期、生长期及停滞期。培养前1－4d细胞从组织块中大量游出，5－7d为延缓期，此期间细胞渐渐开始贴壁，8－18d为生长期，细胞数目迅速增多，生长速度很快，继而进入停滞期，细胞数目增长缓慢，细胞空泡化明显，渐渐走向死亡。结论 HPV感染阳性的喉乳头状瘤细胞在体外生长情况良好，但要建立HPV感染阳性的喉乳头状瘤细胞的动物模型尚需进一步研究。     

新疆部分地区儿童复发性喉乳头状瘤HPV6和HPV11病毒感染在维吾尔族及汉族患者之间的差异

目的：研究新疆部分地区喉乳头状瘤病毒HPV6,HPV11在汉族及维吾尔族儿童复发性喉乳头状瘤（JRRP）患儿中的表达差异。方法：采用聚合酶链反应（PCR）技术对喉乳头状瘤组织中HPV11和HPV6 DNA进行定型分析,结合回顾性分析1996—01—2008—03期间在新疆医科大学第一附属医院耳鼻咽喉科连续收治的42例JRRP患者。结果：HPV6／11阳性检出率97．61％（41／42）,HPV6阳性36．58％（41／15）,HPV11阳性63．41％（41／26）,HPV6阳性组中维族HPV6阳性53．33％（8／15）,汉族HPV6阳性46．67％（7／15）,HPV11阳性组中维族HPVll阳性65．38％（17／26）,汉族HPV11阳性34．61％（9／26）。结论：新疆部分地区JRRP以HPV11,6感染为主,HPV11感染者占多数,HPV病毒类型与维汉间的发病率之间差异无统计学意义。     

鼻腔及鼻窦内翻性乳头状瘤与人乳头状瘤病毒感染及病毒亚型的关系

目的 采用多聚酶链反应(polymerase chain reaction，PCR)检测鼻腔及鼻窦内翻性乳头状瘤(nasal inverted papilloma，NIP)中人乳头状瘤病毒(human papilloma virus，HPV)DNA及其亚型，旨在探讨HPV在NIP发病中的作用及其与预后的关系。方法将28例鼻腔及鼻窦NIP分为无复发组、复发组、癌变组，用聚合酶链反应检测其HPV通用型、6、11、16及18型的感染情况，同时以10例慢性炎症鼻黏膜或炎症性鼻息肉病例为对照。结果28例NIP患者HPV-DNA总阳性率为75％(21例)。无复发组病例HPV-DNA阳性率为42％(5／12)，均为单一的低危型HPV感染(4例为HPV6型，1例为HPV11型)；复发组的13例和癌变组的3例中，均可检出HPV-DNA。复发者以检出HPV6、HPV11型DNA为主，4例具有双重感染。癌变者以检出HPV16、HPV18型DNA为主，其中2例为双重感染。结论NIP的发生与HPV感染密切相关。应用PCR检测HPV及各亚型感染情况有助于预测肿瘤的临床行为及预后，指导临床对高危患者进行重点监测。     

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     

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.     

鼻腔鼻窦内翻性乳头状瘤CEA及AgNOR表达的临床意义

为探索预测鼻内翻性乳头状瘤（NIP）癌变的可能性，采用免疫组化ABC法及胶银染色技术分别对20例NIP共24份标本进行CEA及AgNOR检测，以16例鼻息肉及18例界窦鳞癌为对照组。结果在20例NIP中有4例NIP术后切除大标本局部癌变，而术前标本示不典型增生。在此8价标本中（术前4份，术后4份），CEA全部呈浆膜型阳性，与鼻窦鳞癌CEA表达类型一致。AgNOR计数，术前标本与术后癌变标本其AgNOR颗粒分别为5．83个与8．86个，两者有显著差异，且术前标本AgNOR计数与其它3例不典型增生NIP均属同一组。结论，CEA在NIP中表达的类型在预测NIP癌变的临床应用上比AgNOR计数更有价值。     

低温等离子射频治疗成人喉乳头状瘤的初步观察

目的 探讨低温等离子射频切除术治疗成人喉乳头状瘤的可行性.方法 回顾性分析2008年4月至2010年6月治疗的18例喉乳头状瘤患者的临床资料,其中多发性喉乳头状瘤4例,单发喉乳头状瘤14例,患者均经口气管插管全麻,内镜支撑喉镜下应用7070号等离子射频刀切除肿瘤.结果 术中出血约1～10 ml,平均2 ml,术后无出血及其他并发症.随访6至33个月,中位随访时间18个月,16例患者未见复发;2例分别于术后4个月和8个月复发,再次等离子射频切除术,术后分别随访4个月和12个月,1例再次复发,另1例未见复发.结论 内镜支撑喉镜下应用低温等离子射频切除术治疗成人喉乳头状瘤具有出血少、损伤小等优点,是一种较好的手术方法.

Abstract：

Objective To evaluate the effect and feasibility of coblation treatment for laryngeal papilloma in adult. Methods A total of 18 patients with laryngeal papilloma treated by coblation from April 2008 to June 2010 was retrospectively analysed. There were 4 cases of multiple laryngeal papilloma and 14 cases of single laryngeal papilloma. All of these patients were treated with CoblatorTM Reflex #7070 under general anesthesia without tracheotomy. Results The volumes of blood loss during surgery varied from l ml to 10 ml, 2 ml on average. There was no postoperative bleeding or other complications. Follow-ups ranged from 6 months to 33 months after surgery, median 18 months. Recurrence occurred 4 months and 8 months after surgery in two patients. They were treated with coblation for the second time and followed up for 4 months and 12 months respectively. Recurrence occurred again in one patient. Conclusion Coblation under suspension laryngoscope for laryngeal papilloma in adult was an ideal way due to less bleeding and less damage.     

小儿喉乳头状瘤62例临床分析

目的 :探讨小儿喉乳头状瘤的临床特征。方法 :对 6 2例小儿喉乳头状瘤 ,2 8例在直接喉镜下钳除肿瘤 ,34例行喉显微手术加激光治疗。结果 :随诊 2～ 5年 ,2年治愈率 5 1.6 %。结论 :本病发展快 ,复发率高 ,病变范围广 ,声门下发病率高 ,应用喉显微激光手术及干扰素辅助治疗 ,可更精确切除肿瘤和减少复发 ,并取得较好疗效。     

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.     

Detection of human papillomavirus genome in nasolaryngeal papillomas using digoxigenin labeled DNA probes

It is being reported that human papillomavirus (HPV) has been implicated in the pathogenesis of various neoplastic lesions of the genital organs. To investigate the etiological role of HPV and its types in nasolaryngeal papillomas, we retrospectively analyzed HPV genomes by nucleic acid hybridization methods; for detecting DNA and mRNA, we employed the recently developed nonradioactive (digoxigenin labeled) DNA probes and compared the results by radioisotope methods. In total, 43 cases of papillomatous lesions were examined. They were verruca vulgaris of the nasal vestibule (Nr = 2), nasal inverted papilloma (IP, Nr = 26), and laryngeal papilloma (Nr = 15). HPV types examined were type 2, 6, 11, 16 and 18. Two cases of verruca vulgaris were shown to contain HPV-2 DNA and its mRNA by in situ hybridization. HPV-11 DNA was detected in 3 cases (12%) of nasal inverted papilloma whereas HPV-16 was detected in 1 case (4%); the latter case was associated with squamous cell carcinoma. These results suggest that HPV may be implicated in the development of IP, and HPV-16 may play an important role in the malignant transformation of IP. In the cases of multiple laryngeal papilloma (Nr = 8, one juvenile type and 7 adult type), either HPV-6 or HPV-11 was detected at the high rate (6/8, 75%). The presence of the HPV genomes provides strong evidence for the HPV etiology of these laryngeal papillomas. Whereas in the cases of adult single laryngeal papilloma (Nr = 7), HPV was not detected. Technically, the sensitivity of digoxigenin (DIG) labeled DNA probe was almost same as 35S labeled probe by dot blot hybridization, thus we applied DIG labeled probe to Southern blot hybridization with low background. By in situ hybridization using digoxigenin labeled probes, the rates of HPV detection were almost equal to those by 35S labeled probes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of human papillomavirus subtype and clinical course in respiratory papillomatosis

The relationship of human papillomavirus type 6 (HPV-6) subtypes to the clinical manifestations of respiratory papillomatosis was investigated. DNA was isolated from biopsy specimens of 21 patients and the viral genome analyzed by molecular hybridization. Four subtypes, designated HPV-6c through HPV-6f, were distinguishable by restriction endonuclease cleavage patterns of the viral genome. Patient records were reviewed to identify associations between viral subtype and sex, race, age at onset of papilloma, duration of disease, frequency of operations, history of tracheotomy and anatomical extension of papilloma. HPV-6c was present in 13 cases which were characterized by extensive anatomical spread of disease, higher frequency of operations, and a need for tracheotomy. HPV-6d occurred in 4 black patients with juvenile onset papilloma. HPV-6e was found in 2 white patients — 1 with juvenile onset and 1 with adult onset papilloma. HPV-6f was identified in 2 white patients with adult onset disease.