HPV6b病毒样颗粒免疫治疗儿童喉乳头状瘤临床初步研究

目的 :研究HPV6bL1病毒样颗粒 (VLP)治疗儿童喉乳头状瘤 (JLP)的安全性和免疫原性。方法 :应用基因工程制备的HPV6bL1VLP 5、10、2 5 μg 3种剂量递增方法对 10例严重复发性JLP患儿进行免疫接种 ,记录不良反应及行血、尿常规和生化检测 ,ELISA法检测血清特异性HPV6bL1VLP抗体 ,对 7例患儿进行迟发性超敏反应 (DTH)试验 ,纤维喉镜随访观察喉部病变情况。结果 :接种后患儿无局部和全身不良反应 ,血清均能产生特异性的中和抗体 ,接种前 3天和 3种剂量完成后及开始治疗 1年后的血清抗体吸收度A均值分别为 0 .110± 0 .0 35 ,0 .310± 0 .0 12 ,0 .5 87± 0 .0 12 ,0 .75 2± 0 .0 19,0 .772± 0 .0 13。第 1剂量完成后与接种前 3天A均值比较 ,第 2剂量与第 1剂量完成后比较 ,第 3剂量与第 2剂量完成后比较 ,接种 1年后与对照组比较 ,各组间差异均有统计学意义 (均P <0 .0 1)。 7例行DTH试验的患儿均呈阳性反应。经免疫治疗后的 10例患儿未见复发。结论 :HPV6bL1VLP对JLP具有安全性和免疫原性 ,可成为防治JLP的有效疫苗。     

HPV11对小儿喉乳头状瘤预后的影响

目的 :研究人乳头状瘤病毒 (HPV)型别对小儿喉乳头状瘤 (JLP)预后的影响。方法 :应用聚合酶链反应结合斑点杂交技术对 2 5例JLP的石蜡标本进行HPV定型分析 ,并统计HPV11、HPV6 感染组的气管切开率和术后复发率。结果 :HPV总检出率为 96.0 % ,其中HPV11为 5 6.0 % ,HPV6 为 4 0 .0 % ,HPV16、18、33无一例阳性。HPV11感染组的气管切开率为 71.4 % ,术后复发率为 85 .7% ;HPV6 感染组的气管切开率为 3 0 .0 % ,术后复发率为4 0 .0 %。两组分别比较 ,其差异均有显著性意义 (P <0 .0 5 )。结论 :HPV6、11与JLP发生密切相关 ,HPV11感染与JLP的喉梗阻和术后复发率相关 ,HPV11感染可作为JLP预后评判的重要依据。     

Human papilloma virus infection and expression of p16 protein in laryngeal papilloma and laryngeal carcinoma]

OBJECTIVE: To evaluate the role of human papilloma virus (HPV) infection and inactivation of p16 gene in laryngeal papilloma (LP) and laryngeal squamous cell carcinoma (LC). METHODS: HPV consensus primers direct in situ polymerase chain reaction (ISPCR) and immunohistochemical method were applied to detect the presence of HPV genomes (1, 6, 8, 11, 13, 16, 18, 30, 31, 32, 33, 45, 51) and the expression of p16 protein respectively in 93 cases of formalin-fixed, paraffin-imbedded specimens, which contained 46 cases of LPs [adult-onset laryngeal papilloma (ALP) 21, juvenile-onset laryngeal papilloma (JLP)25], 26 cases of LCs, 6 cases of normal tissues adjacent to carcinoma, and 15 cases of vocal noduli. RESULTS: (1) The difference of positive rates of HPV-DNA in JLP group (84%, 21/25) and other groups were statistically significant (chi 2 test, P < 0.05). The difference of positive rates of HPV-DNA in ALPs(38.1%, 8/21), in LCs(19.2%, 5/26), in vocal noduli(0%, 0/15), and in normal tissues adjacent to carcinoma(0%, 0/6) were not significant statistically (chi 2 test or Fisher's exact probability test, P > 0.05). (2) The positive rates of expression of p16 protein in ALP group(57.1%, 12/21) and LC group(38.5%, 10/26) were significantly lower than that in vocal nodule group(93.3%, 14/15), in JLP group(88%, 22/25), and in normal tissues adjacent to carcinoma group (100%, 6/6) (chi 2 test or Fisher's exact probability test, P > 0.05). There were no significant differences of positive rates of expression of p16 protein between ALP group and LC group, and between JLP group and vocal nodule group (chi 2 test, P > 0.05). (3) In LPs, the difference of positive rates of p16 protein expression between HPV positive cases and HPV negative cases was significant statistically (chi 2 test, P < 0.05). In LCs, there was no difference in p16 protein expression rate between the two teams(Fisher exact probability test, P > 0.05). CONCLUSION: The pathogenesis of JLP is closely associated with HPV infection and not associated with the inactivation of p16 gene. Conversely, the pathogenesis of ALP and LC is associated with the inactivation of p16 gene and not associated with the HPV infection.     

喉癌和喉乳头状瘤组织中人乳头状瘤病毒和p16蛋白的检测

目的探讨人类乳头状瘤病毒（humanpapillomavirus,HPV）感染和抑癌基因p16的失活与喉癌和喉乳头状瘤（laryngealpapilloma,LP）发生的相关性,以进一步阐明喉癌和LP的病因和发病机理。方法收集LP46例,其中成人型喉乳头状瘤（adult-onsetLP,ALP）21例,青少年型喉乳头状瘤（juvenile-onsetLP,JLP）25例、喉癌26例、癌旁正常组织6例、声带小结15例,用标记的HPV1,6,8,11,13,16,18,30,31,32,33,45,51通用引物直接法原位聚合酶链反应（polymerasechainreaction,PCR）方法和免疫组化（SP法）方法分别检测HPV-DNA和p16蛋白。结果①HPV阳性率JLP组（84%,21/25）显著高于ALP组（38.1%,8/21）、喉癌组（19.2%,5/26）、声带小结组（0/15）和癌旁组织组（0/6）（χ     

小儿喉乳头状瘤HPV-DNA及体液免疫检测

目的：探讨小儿喉乳头状瘤（ＪＬＰ）人乳头瘤病毒（ＨＰＶ）感染途径及发病机理。方法：采用ＰＣＲ及ＰＣＲ产物斑点杂交技术检测ＪＬＰ组织ＨＰＶ－ＤＮＡ;散射免疫比浊法测定血清Ｉｇ及补体Ｃ３。结果：ＪＬＰ组织ＨＰＶ总感染率为９５％（１９／２０）,其中ＨＰＶ。型为５５％（１１／２０）,ＨＰＶ１１为３０％（６／２０）,ＨＰＶ６＋１１型为１０％（２／２０）;ＪＬＰ患者血清ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｃ３值正常,对照     

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。     

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.     

原位杂交在成年和幼年型喉乳头状瘤HPV病因学的对比研究

探讨成年和幼年型喉乳头状瘤ＨＰＶ感染发病差异及其影响因素。方法：用地高辛配基（Ｄｉｇｏｘｉｇｅｎｉｎ）标记ＨＰＶ６和ＨＰＶ１１型作探针，原位核酸杂交方法在２９例成年型喉乳头状瘤（ＡＬＰ）和２１例幼年型喉乳头状瘤（ＪＬＰ）石蜡包埋标本检测ＨＰＶ同源序列。结果：ＡＬＰＨＰＶ６和ＨＰＶ１１阳性率分别为４１４％（１２／２９）和４８３％（１４／２９）；ＪＬＰＨＰＶ６及ＨＰＶ１１阳性率均为７６２％（１６／２１）。ｘ２统计示：两型喉乳头状瘤ＨＰＶ６及ＨＰＶ１１阳性率明显不同（ＨＰＶ６ｘ２＝５９９，ＨＰＶ１１ｘ２＝３９５，Ｐ均小于００５）。结论：１）ＡＬＰ和ＪＬＰＨＰＶ感染发病存在差异。２）ＡＬＰ除了ＨＰＶ感染外，其促发因素不可忽视，ＪＬＰ更倾向于依赖ＨＰＶ感染而发病。     

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.     

人乳头状瘤病毒与鼻内翻性乳头状瘤的关系

为探讨人乳头状瘤病毒（ＨＰＶ）感染与鼻内翻性乳头状瘤（ＩＰ）发病及其恶变的关系，研究选取组织病理确认为ＩＰ（３６例）和ＩＰ癌变（１６例）的石蜡包埋标本，采用多聚酶链反应（ＰＣＲ）方法对标本进行ＨＰＶ相关ＤＮＡ序列扩增。结果显示：３６例ＩＰ组织有２１例（５８．３％）为ＨＰＶ阳性；１６例ＩＰ癌变组织中有１１例（６８．８％）阳性。经统计学处理，二者间无显著性差异（Ｐ〉０．０５）．提示ＨＰＶ感染在ＩＰ的发     

2',5'-Oligoadenylate synthetase activity analysis and human papilloma virus typing as prognostic factors in patients with recurrent respiratory papillomatosis

OBJECTIVE: Determination of early prognostic factors in patients with recurrent respiratory papillomatosis is extremely important, so the major goal of our prospective, multicentre study was to evaluate (1) the feasibility of various factors to determine prognosis of the clinical course, as well as (2) the response to interferon-alpha therapy in recurrent respiratory papillomatosis. METHODS: Forty-two patients with recurrent respiratory papillomatosis were treated with interferon-alpha (3 MU/m(2) three times per week; mean therapy duration was 2.7 +/- 1.8 years) in 1983-1994 and followed-up until 2003. Human papilloma virus (HPV) type, recurrent respiratory papillomatosis severity and 2',5'-oligoadenylate synthetase activity were determined by standard methods and analysed for correlation with the results of long-term clinical outcome. RESULTS AND CONCLUSION: Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.     

High incidence of malignant transformation of laryngeal papilloma in Taiwan

OBJECTIVES: Papillomas of the larynx include solitary laryngeal papilloma and recurrent respiratory papillomatosis. This study investigated the incidence of malignant transformation and assessed possible risk factors for laryngeal papillomas. STUDY DESIGN: A prospective, longitudinal study. METHODS: Twenty-six consecutive laryngeal papilloma patients were prospectively studied for 5 or more years, and each patient was periodically examined at 3 to 6 month intervals. A detailed epidemiologic questionnaire was administered at the initial visit. After enrollment, tissue obtained during each laryngeal surgery was examined by polymerase chain reaction assay for human papilloma virus (HPV) and typing. RESULTS: During 237 person-years of follow-up, six new, pathologically confirmed cases of laryngeal carcinoma were ascertained (incidence 2.5/100 person-years), and all were associated with HPV-6 or HPV-11. Malignant transformation revealed no correlation with the following: age less than 3 years at diagnosis, sex, history of tobacco use, history of alcohol consumption, family history of laryngeal cancer, or type of laryngeal papilloma. Laryngeal papilloma without demonstrable HPV DNA was the only significant risk factor for malignant transformation (P < .05). The cumulative risk of malignant transformation in subjects without demonstrable HPV DNA was significantly higher than that in HPV-positive patients (relative risk, 8.0; 95% confidence interval, 1.1-60.3; P = .05). CONCLUSIONS: A relatively high incidence of malignant transformation of laryngeal papilloma was noted in Taiwanese patients. Patients without demonstrable HPV DNA require more frequent follow-up and may benefit from anti-HPV vaccinations.     

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、３３５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５４．２％（１９／３５）,ＨＰＶ１１型感染率为２５．７％（９／３５）,多重型别ＨＰＶ６＋１１感染率为１１．     

Pharyngeal squamous cell papilloma in adult Japanese: comparison with laryngeal papilloma in clinical manifestations and HPV infection

A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.     

HPV在鼻喉部几种常见病中的表达

目的评价鼻喉部几种常见病（鳞状上皮及腺上皮发生的癌、乳头状瘤、息肉,炎性病变）与人乳头状瘤病毒（human papilloma virus,HPV）感染的关系。方法用免疫组化S P染色法测定组织中HPV6、11、16、18、31、33、42、51、52、56、58的表达。结果HPV表达率在鳞癌为41.4%,腺癌20.0%,鳞状上皮乳头状瘤47.6%,腺上皮乳头状瘤20.0%,鳞状上皮息肉7.1%,腺上皮息肉3.6%,过敏性鼻炎和鼻窦炎中无表达。相关分析显示,鳞癌和腺癌、鳞状上皮乳头状瘤和腺上皮乳头状瘤、鳞状上皮息肉和腺上皮息肉之间HPV感染率差异无统计学意义（P＞0.05）。鳞状上皮癌+鳞状上皮乳头状瘤HPV感染率之和与腺上皮癌+腺上皮乳头状瘤HPV感染率之和比较,鳞癌+腺癌+鳞状上皮乳头状瘤+腺上皮乳头状瘤HPV感染率之和与鳞状上皮息肉+腺上皮息肉HPV感染率之和比较,差异均有统计学意义（P＜0.05）。结论鼻喉部肿瘤性病变的发生发展与HPV感染有密切的关系,HPV感染鳞状上皮的概率可能高于腺上皮。     

HPV感染与鼻内翻性乳头状瘤复发及恶变相关的Meta分析

 目的探讨人乳头状瘤病毒（HPV）与鼻腔鼻窦内翻性乳头状瘤（SNIP）发生、复发及恶变的关系。方法检索Pubmed、Web of science、 Embase、Cochrane Library、CNKI、维普、中国知网及万方等数据库,查找2000~2017年国内外公开发表的HPV与SNIP发生、复发及恶变相关的所有病例对照研究文献,应用RevMan 5.3统计软件对各研究原始数据进行统计分析。结果Meta分析示SNIP组HPV感染率明显高于对照组(P<0.01,OR=19.72,95%CI为7.91~49.18);复发组HPV感染率明显高于对照组(P<0.01,OR=3.10,95%CI为1.90~5.08);恶变组HPV感染率明显高于对照组（P<0.01,OR=2.09,95%CI为1.41~3.09）。结论HPV感染与SNIP的发生、复发及恶变密切相关。     

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998

OBJECTIVES: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas. STUDY DESIGN: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells. RESULTS: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression. CONCLUSION: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.     

The prevalence of human papilloma virus infection in sinonasal inverted papilloma specimens classified by histological grade

BACKGROUND: Histological analysis suggests that inverted papilloma (IP) tumorigenesis may occur through a stepwise series of discrete events. The association between human papilloma virus (HPV) and IP has been described at varying incidences. The purpose of this study was to evaluate the prevalence of the HPV subtypes in a large series of IP specimens classified by histological grade. METHODS: Fifty-seven paraffin-embedded specimens of Korean population were available for study. Each specimen was graded according to a four-stage histological grading system (stages I and II, benign IP; stage III, dysplastic IP; stage IV, carcinoma arising from IP). A representative section of IP specimen was isolated through laser capture microdissection (7.5- to 10-mum laser spot size). Subsequently, DNA extraction and HPV genotyping with the HPV DNA chip test (Biomed Lab Co., Seoul, Korea) was performed. The HPV DNA chip contained 22 type-specific probes that consisted of 15 high-risk subtypes and 7 low-risk subtypes. RESULTS: Histological grading was as follows: 5, grade I; 23, grade II; 22, grade III; and 7, grade IV. Seven of 57 specimens (12.3%) showed HPV DNA. All of the HPV(+) cases showed HPV DNA in early grade (grades I and II) IP lesions. No higher grade (grades III and IV) IP tumors showed HPV DNA. Among the seven HPV(+) cases, five were high-risk subtypes and two were unspecified subtypes. CONCLUSION: HPV infection, mainly high-risk subtypes, occurs in benign IP as an early event during the multistep tumorigenesis of IP. Cumulative other genetic insults may be required to progress from benign IP (grades I and II) to dysplastic IP (grade III) and carcinoma arising from IP (grade IV).     

Inverted naso-sinusal papilloma: analytic study on 13 cases

OBJECTIVES: Inverted nasosinusal papilloma is a rare tumorous process involving mucosa of nasal fossa and paranasal sinus unilaterally. The authors studied inverted naso-sinusal papilloma observed and treated in ENT and Head and Neck department at Brazzaville University Hospital. MATERIAL AND METHODS: Retrospective study concerning 13 patients treated between 1988 and 2001. RESULTS: The average age is 34 years (range: 16 to 60 years); old nasal obstruction is the main symptom (12 cases); the diagnosis is histologic; association with Killian polyp (1 case), human papilloma virus infection (1 case) and rhinosporidiosis (1 case); large surgical removal (Caldwell-Luc, para-latero-nasal) and polypectomy associated to diathermy of tumorous insertion place permitted to have satisfactory results; the recurrencies were observed in four cases from 7 months to 10 years (average: 4 years); malignant transformation is noted in 2 cases with one case of inverted papilloma combined to Human Papilloma Virus infection. CONCLUSION: All naso-sinusal polypoid should have a histological study. Patients must be followed-up regularly; this is very difficult in Africa.