鼻腔鼻窦内翻性乳头状瘤人类乳头状瘤病毒DNA检测

为了解鼻腔鼻窦内翻性乳头状瘤与人类乳头状瘤病毒（ＨＰＶ）之间的关系，采用聚合酶链反应，对３８例患者的４４个鼻腔鼻窦内翻性乳头状瘤的病理组织蜡块进行ＨＰＶ－ＤＮＡ的检测。结果显示，３８例中３０例患者的３０个瘤组织蜡块呈ＨＰＶ阳性，总感染率为６８．２％，其中３０例次ＨＰＶ１１型阳性（６８．２％），１８例次ＨＰＶ１６型阳性（４０．９％），２例次ＨＰＶ１８型阳性（４．５％），其中１８例ＨＰＶ１１，１６、２     

鼻腔鼻窦内翻性乳头状瘤人类乳头状瘤病毒DNA检测

为了解鼻腔鼻窦内翻性乳头状瘤与人类乳头状瘤病毒（ＨＰＶ）之间的关系，采用聚合酶链反应，对３８例患者的４４个鼻腔鼻窦内翻性乳头状瘤的病理组织蜡块进行ＨＰＶ－ＤＮＡ的检测。结果显示，３８例中３０例患者的３０个瘤组织蜡块呈ＨＰＶ阳性，总感染率为６８．２％，其中３０例次ＨＰＶ１１型阳性（６８．２％），１８例次ＨＰＶ１６型阳性（４０．９％），２例次ＨＰＶ１８型阳性（４．５％），其中１８例ＨＰＶ１１，１６、２例ＨＰＶ１１，１８呈双重感染。试验表明，ＨＰＶ与鼻腔鼻窦内翻性乳头状瘤在病因上有一定的相关性。     

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。     

人疱疹病毒6型对EB病毒复制影响的研究

目的探讨人疱疹病毒６型（ＨＨＶ６）对ＥＢ病毒（ＥＢＶ）复制的影响。方法用ＨＨＶ６感染Ｒａｊｉ细胞和ＥＢＶ转化的淋巴细胞（ＬＣＬ），并用抗ＨＨＶ６单克隆抗体（ＭＡｂ）作免疫萤光分析（ＩＦＡ）确定ＨＨＶ６已感染这二种细胞。用抗ＥＢＶ人血清作ＩＦＡ观察ＥＢＶ抗原表达。结果ＨＨＶ６感染Ｒａｊｉ细胞后可见细胞病变效应（ＣＰＥ）；而ＬＣＬ未见ＣＰＥ。这二种细胞株用抗ＨＨＶ６的ＭＡｂ作ＩＦＡ均检出ＨＨＶ６，而对照组未检出ＨＨＶ６；用抗ＥＢＶ人血清作ＩＦＡ，感染ＨＨＶ６的二种细胞中均检出ＥＢＶ抗原。结论ＨＨＶ６促进了ＥＢＶ抗原表达，并提示在鼻咽癌的发生中ＨＨＶ６和ＥＢＶ可能起协同致病作用。     

EB病毒感染与鼻腔鼻窦非霍奇金淋巴瘤关系的研究

目的探讨ＥＢ病毒与鼻腔鼻窦非霍奇金淋巴瘤的关系。方法采用多聚酶链反应（ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ，ＰＣＲ）技术检测２２例原发性鼻腔、鼻窦非霍奇金淋巴瘤（其中Ｔ细胞型１３例，Ｂ细胞型９例）瘤组织及２０例炎症性鼻腔鼻窦粘膜组织中ＥＢ病毒ＤＮＡ酶基因。结果发现实验组中１４例ＥＢＶＤＮＡ酶基因阳性，Ｔ细胞型１３例中９例阳性，Ｂ细胞型９例中５例阳性，总阳性率为６３．６％；对照组２０例中４例ＥＢＶＤＮＡ酶基因阳性，阳性率为２０％，实验组与对照组比较阳性率差异有显著性（χ２检验，Ｐ＜０．００５）。结论ＥＢＶ感染不仅存在于Ｂ细胞型非霍奇金淋巴瘤，也存在于Ｔ细胞型的非霍奇金淋巴瘤中。     

EB病毒感染与鼻腔鼻窦非霍奇金淋巴瘤关系的研究

目的 探讨ＥＢ病毒与鼻腔鼻窦非霍奇金淋巴瘤的关系。方法 采用多聚酶链反应（ＰＣＲ）技术检测２２例原发性鼻窦、鼻窦非霍奇金淋巴瘤（其中Ｔ细胞型１３例，Ｂ细胞型９例）瘤组织及２０例炎症性鼻腔鼻窦粘膜组织中ＥＢ病毒ＤＮＡ酶基因。结果 发现实验组中１４例ＥＢＶ－ＤＮＡ酶基因阳性，Ｔ细胞型１３例中９例阳性，Ｂ细胞型９例中５例阳性，总阳性率为６３．６％；对照组２０例中４例ＥＢＶ－ＤＮＡ酶基因阳性，阳性率为２０     

国人喉癌与人类乳头状瘤病毒相关性的研究

本项研究对１２４例喉不同病变的新鲜组织标本，采用共同引物和多重引物ＰＣＲ的方法，进行ＨＰＶＤＮＡ检测。用共同引物ＰＣＲ检测ＨＰＶ＿（６，１１，１６，１８，３１，３３，３５，４２，５８）九个型别的感染，阳性病例再用多重引物ＰＣＲ进一步分型。结果，①喉癌组：ＨＰＶ感染的总阳性率为４９．１％，其中ＨＰＶ＿（１８）型阳性率１５．８％，ＨＰＶ＿（１６）型为１２．３％，ＨＰＶ＿（１６）和＿（１８）双重型感染为５．３％，ＨＰＶ＿（６／１１）和＿（１８）型混合感染为３．５％，其它型为１２．３％。②颈转移淋巴结组：总阳性率为２１．４％，其中ＨＰＶ＿（１６）、ＨＰＶ＿（１８）及ＨＰＶ＿（１６）和＿（１８）双重型感染各为７．１％。③癌前病变组：ＨＰＶ感染阳性率为１１．１％，为ＨＰＶ＿（６／１１）和＿（１８）型混合感染。④声带息肉组：阳性率７．１％，为ＨＰＶ＿（６／１１）型感染。⑤癌旁及癌周正常喉组织：均为ＨＰＶＤＮＡ阴性。本文对ＨＰＶ在喉癌中致病作用进行了讨论。     

上呼吸道乳头状瘤HPVDNA的检测

应用多重引物ＰＣＲ技术对４７例复发性呼吸道乳头状瘤病（ＲＲＰ）和９例声带息肉石蜡包埋组织中ＨＰＶ６／１１、１６、１８ＤＮＡ进行了检测。结果发现：①ＲＲＰ组织中ＨＰＶ６／１１ＤＮＡ的阳性率为６８．１％（３２／４７），其中喉乳头状瘤、口咽乳头状瘤、鼻腔和鼻前庭乳头状瘤组织中ＨＰＶ６／１１ＤＮＡ的阳性率分别为７０．４％（１９／２７）、６６．７％（４／６）和６４．３％（９／１４）；②所有ＲＲＰ标本中均未发现特异性的ＨＰＶ１６和ＨＰＶ１８ＤＮＡ；③９例声带息肉标本中四种型号的ＨＰＶＤＮＡ全部阴性。实验结果表明，ＲＲＰ的发病与ＨＰＶ６／１１感染密切相关。多重引物ＰＣＲ检测ＨＰＶＤＮＡ具有敏感、特异、快速、简便等优点，适合于临床广泛开展和进行流行病学调查。     

人咽喉部良恶性肿瘤与乳头状瘤病毒关系的研究

采用免疫组化及ＤＮＡ斑点杂交技术检测人咽喉部乳头状瘤及鳞状细胞癌组织中人乳头状瘤病毒（ＨＰＶ）壳蛋白抗原及ＨＰＶ６、１１、１６、１８型ＤＮＡ。１１例乳头状瘤ＨＰＶ抗原与ＨＰＶ ＤＮＡ阳性率均为４５．５％。２２例鳞状细胞癌ＨＰＶ抗原阳性率２２．７％，ＨＰＶ ＤＮＡ阳性率２７．３％。乳头状瘤ＨＰＶ检出率与组织学检查的结果相符。提示咽喉部乳头状瘤及鳞状细胞癌的发生、发展与ＨＰＶ感染有关。     

喉癌人乳头瘤病毒感染和p53蛋白表达的研究

对４４例喉鳞癌和１６例声带息肉患者采用原位核酸杂交技术探测其人乳头瘤病毒（ＨＰＶ）６Ｂ，１１，１６，１８型ＤＮＡ同源序列及ＬＳＡＢ免疫组化法探测其Ｐ５３蛋白的表达，结果：（１）喉癌与ＨＰＶ１６／１８杂交阳性率为４３．２％（１９／４４），声带息肉为１２．５％（２／１６）（Ｐ〈０．０５）（２）喉癌ｐ５３蛋白阳性率为５６．８％（２５／４４），声带息肉全部为阴性；（３）喉癌ＨＰＶ１６／１８杂交及ｐ５３蛋白     

Nasopharyngeal and adjacent neoplasms: a clinico-pathologic and immunologic study.

Thirteen cases of nasopharyngeal carcinoma (NPC) and 16 cases of non-NPC tumors in the nasopharynx or in adjacent locations were investigated clinically, immunologically, and pathologically. All tumors were classified according to the TNM classification, and the stage and course of the disease was correlated with the histological tumor type, the T- and B-cell distribution in tumor tissue and in the peripheral blood, as well as with antibody titers against Epstein-Barr virus (EBV). The results showed a positive correlation of decreased T- and B-cells in tumor tissue and of decreased T-cells in the peripheral blood with the extend of the tumor in both NPC and non-NPC cases, with some exceptions of lymphocyte rich neoplasms (lymphoepithelial carcinoma and malignant lymphoma). Antibodies against EBV (early antigen and capsid antigen) became progressively elevated with increasing tumor stage in NPC-cases but not in non-NPC cases. The latter, however, was observed only in two histological types of NPC's: anaplastic carcinoma and lymphoepithelial carcinoma; titers in the remaining tumor types stayed insignificant.     

Nasopharyngeal and adjacent neoplasms: A clinico-pathologic and immunologic study

Summary Thirteen cases of nasopharyngeal carcinoma (NPC) and 16 cases of non-NPC tumors in the nasopharynx or in adjacent locations were investigated clinically, immunologically, and pathologically. All tumors were classified according to the TNM classification, and the stage and course of the disease was correlated with the histological tumor type, the T- and B-cell distribution in tumor tissue and in the peripheral blood, as well as with antibody titers against Epstein-Barr virus (EBV). The results showed a positive correlation of decreased T- and B-cells in tumor tissue and of decreased T-cells in the peripheral blood with the extend of the tumor in both NPC and non-NPC cases, with some exceptions of lymphocyte rich neoplasms (lymphoepithelial carcinoma and malignant lymphoma). Antibodies against EBV (early antigen and capsid antigen) became progressively elevated with increasing tumor stage in NPC-cases but not in non-NPC cases. The latter, however, was observed only in two histological types of NPC's: anaplastic carcinoma and lymphoepithelial carcinoma; titers in the remaining tumor types stayed insignificant.Immunopathologic and tissue culture studies were supported by grants of the Volkswagen Foundation, the German Science Foundation, and the State Ministry of Science and Research of Northrhine-Westfalia     

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     

Epstein-Barr virus latent membrane protein-1 (LMP-1) expression in oral squamous cell carcinoma

OBJECTIVES: Epstein-Barr virus (EBV) is frequently associated with malignant cell transformation through the action of the oncoprotein latent membrane protein-1 (LMP-1). The present study aimed to determine the presence of EBV in oral squamous cell carcinomas (OSCCs) and the expression of LMP-1 in neoplastic cells of EBV-positive OSCCs. STUDY DESIGN/METHODS: In a retrospective study of 78 OSCCs, we investigated the presence of the DNA of EBV by polymerase chain reaction, the expression of the oncoprotein LMP-1 by immunohistochemistry, and the presence of EBV-encoded RNA (EBER) by in situ hybridization. RESULTS: EBV DNA was detected in 19.2% of the cases. Expression of LMP-1 in neoplastic cells was found in 85.7% of the EBV-positive OSCCs. EBV presence was significantly more frequent (P <.05) in OSCCs localized on the lateral tongue. EBV-positive OSCCs more frequently presented (P <.05) greater nuclear atypia. CONCLUSION: EBV can appear in latent form in OSCC and express its main oncoprotein, LMP-1.     

Expression of cyclin-dependent kinase inhibitor 2A 16, tumour protein 53 and epidermal growth factor receptor in salivary gland carcinomas is not associated with oncogenic virus infection

It is known that human papillomavirus (HPV) infection can cause squamous cell neoplasms at several sites, such as cervix uteri carcinoma and oral squamous carcinoma. There is little information on the expression of HPV and its predictive markers in tumours of the major and minor salivary glands of the head and neck. We therefore assessed oral salivary gland neoplasms to identify associations between HPV and infection-related epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitor 2A (CDKN2A/p16) and tumour protein p53 (TP53). Formalin-fixed, paraffin-embedded tissue samples from oral salivary gland carcinomas (n=51) and benign tumours (n=26) were analysed by polymerase chain reaction (PCR) analysis for several HPV species, including high-risk types 16 and 18. Evaluation of EGFR, CDKN2A, TP53 and cytomegalovirus (CMV) was performed by immunohistochemistry. Epstein–Barr virus (EBV) was evaluated by EBV-encoded RNA in situ hybridisation. We demonstrated that salivary gland tumours are not associated with HPV infection. The expression of EGFR, CDKN2A and TP53 may be associated with tumour pathology but is not induced by HPV. CMV and EBV were not detectable. In contrast to oral squamous cell carcinomas, HPV, CMV and EBV infections are not associated with malignant or benign neoplastic lesions of the salivary glands.     

Etiology of sinonasal inverted papilloma: A narrative review

ObjectiveSinonasal inverted papilloma (IP) is a benign and uncommon tumor of the nasal cavity and paranasal sinuses with a tendency for recurrence and even malignant transformation. Though the morphology and clinical behavior of this lesion has been well described, its etiology remains controversial.MethodsComputerized searches were performed in PubMed, Scopus, and Google scholar through May 2015. In this review, etiologic factors including human papilloma virus (HPV), Epstein–Barr virus (EBV), cell cycle related proteins and angiogenic factors, occupational and environmental exposures, and chronic inflammation, will be discussed.ResultsMany studies indicate that HPV has been detected in a significant percentage of IP, while EBV has not been shown to be significantly associated. Certain cell cycle regulatory factors and angiogenic proteins contribute to the dysregulation of proliferation and apoptosis, and facilitate migration and tumor invasion. Occupational exposures, such as welding and organic solvents, have been implicated, and smoking seems more critical to recurrence and dysplasia rather than initial IP occurrence. Chronic inflammation may also have a causative relationship with inverted papilloma, but the mechanism is unclear.ConclusionsThough etiology of sinonasal IP remains controversial, the studies reviewed here indicate a role for viral infection, cell cycle and angiogenic factors, environmental and occupational exposure, and chronic inflammation. Further study on etiologic factors is necessary for clinical guidance and therapeutic targets.     

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.     

Human papillomavirus (HPV) in sinonasal papillomas: A study of 78 cases using in situ hybridization and polymerase chain reaction

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.     

Epstein-Barr Virus and Human Papillomavirus in Snuff-induced Lesions of the Oral Mucosa

Epstein-Barr virus (EBV) and human papillomavirus (HPV) have been associated with benign as well as malignant oral lesions. We examined 43 patients with snuff-induced lesions and 22 control patients with clinically healthy oral mucosa for the presence of HPV and EBV. Polymerase chain reaction was performed on fresh frozen oral biopsies with degenerate consensus primers for HPV and nested primers for EBV. None of the 43 snuff-induced lesions or the 22 control biopsies were HPV-positive. Seven of the 43 (16.3%) snuff-induced lesions and one of the 22 (4.5%) controls were positive for EBV. The snuff-induced lesions were classified according to clinical severity, grade 1 lesions being the least severe and grade 4 the most severe. Eleven percent of grade 2 lesions, 15.8% of grade 3 lesions and 20% of grade 4 lesions were EBV-positive. Neither EBV nor HPV seem to be associated with snuff-induced lesions.