人乳头瘤病毒,疱疹病毒I型及人巨细胞病毒与口腔鳞癌关系的研究

目的：研究口腔鳞癌与人乳头瘤病毒（ＨＰＶ）、孢疹病毒Ｉ型（ＨＳＶ－Ｉ）和人巨细胞病毒（ＨＣＭＶ）的关系。方法：采用斑点杂交和ＰＣＢ技术检验３２例口腔鳞癌、１４例口腔白斑和１０例正常口腔粘膜中ＨＰＶ１６、ＨＳＶ－Ｉ及ＨＣＭＶＤＮＡ。结果：在正常口腔粘膜、白斑及口腔鳞癌中ＨＰＶ１６、ＨＳＶ－１及ＨＣＭＶＤＮＡ感染率分别为０％、３５．７％、５０．０％、４０．０％、５０．０％、４３．３％和０％、１４．３％、２８．１％,口腔鳞癌及白斑组织中ＨＰＶ１６－ＤＮＡ的检出率均高于正常口腔,且差别具有显著性（ｐ〈０．０５）;但ＨＳＶ－Ｉ和ＨＣＭＶＤＮＡ在口腔疾患中的检出率与正常比较无显著差别（ｐ〈０．０５）。结论：ＨＰＶ１６感染与口腔鳞癌的发生相关;ＨＳＶ－Ｉ和ＨＣＭＶ可能参予口腔鳞癌的发生及发展,并且与ＨＰＶ１６有协同致癌的作用     

人乳头瘤病毒16型在口腔癌及癌旁组织中的存在状态

采用斑点杂交和Ｓｏｕｔｈｅｒｎ印迹杂交检测２５例口腔鳞癌及其相应癌旁组织中的人乳头瘤病毒（ＨＰＶ）１６型ＤＮＡ，口腔癌ＨＰＶ１６ＤＮＡ的阳性率为２４．０％（６／２５），癌旁组织为８．０％（２／２５）。经ＢａｍＨＩ、ＰｓｔＩ酶切杂交后出现的阳性区带显示ＨＰＶ１６ＤＮＡ在口腔癌及癌旁组织中均以游离状态存在。作者推测ＨＰＶ１６ＤＮＡ在口腔癌的致癌机理中可能作为一个协作因子发生作用。     

口腔鳞状细胞癌与人乳头状瘤病毒感染的关系

本文用抗牛乳头状瘤病毒（ＢＰＶ）的抗血清对３１例口腔鳞状细胞癌中的人乳头状瘤病毒（ＨＰＶ）结构抗原进行检测，证明其中３０例口腔鳞状细胞癌中ＨＰＶ结构抗原一，说明口腔癌的发病与ＨＰＶ感染有密切关系，对防治ＨＰＶ感染，减少口腔癌的发病有着重要意义。     

人乳瘤病毒16型和EB病毒感染与口腔鳞癌关系

用多聚酶链反应技术为２１例口腔鳞癌及癌旁正常组织成对标本中的人乳头瘤病毒１６型（ＨＰＶ１６）和ＥＢ病毒（ＥＢＶ）ＤＮＡ作检测。结果口腔鳞癌和癌旁正常组织ＨＰＶ１６ＤＮＡ阳性率分别为５２．４％和１４．３％，ＥＢＶ为８５．７％和３３．３％，ＨＰＶ１６和ＥＢＶ均为阳性者分别为４７．６％和９．５％，癌组织和癌旁正常组织间统计学上均有显著性差异。提示口腔粘膜ＨＰＶ１６或ＥＢＶ感染均与口腔鳞癌发生有关。ＨＰＶ１６和ＥＢＶ在口腔粘膜感染可能有协同致口腔鳞癌作用。     

口腔粘膜白斑和鳞癌组织凋亡相关蛋白Bcl-2和Bax的表达研究

目的研究凋亡相关蛋白Bcl-2、Bax在口腔正常粘膜,上皮异常增生和鳞癌组织中的表达及意义。方法采用免疫组织化学方法检测10例正常口腔粘膜,10例单纯性增生上皮,30例异常增生上皮,33例鳞癌石蜡包埋样本中Bcl-2、Bax的表达。结果Bcl-2在正常粘膜、单纯增生和异常增生白斑表达情况基本一致,显弱阳性表达且局限于基底层细胞.鳞癌组织中Bcl-2表达明显高于正常组和白斑组(P＜0.05),且随组织分化程度的降低,Bcl-2的表达逐步加强。Bax在正常粘膜、白斑和鳞癌组中总的阳性率无明显差异,但表达强度不同。正常组Bax弱表达局限于角化层,异常增生白斑组中随异常增生程度的增高,Bax表达加强且遍布上皮全层。鳞癌组织中高分化鳞癌的Bax表达明显高于低分化鳞癌。结论Bax蛋白表达水平代偿性增高是口腔癌前病损发生发展中的早期事件,Bcl-2可能并不参与癌前病变的发生,Bcl-2表达加强和Bax表达下降在促进肿瘤细胞异常增殖的同时,进一步抑制细胞的凋亡导致口腔癌最终的发生和发展。     

口腔癌中人乳头瘤病毒16型和Ha-ras癌基因点突变的研究

目的 检验口腔癌中的人乳头瘤病毒（ＨＰＶ）１６型ＤＮＡ和Ｈａ－ｒａｒ癌基因的点突变,探讨ＨＰＶ１６型和Ｈａ－ｒａｓ癌基因的点突变与口腔癌之间的关系。方法 应用多聚酶链反应（ＰＣＲ）技术扩增ＨＰＶ１６ＤＮＡ和Ｈａ－ｒａｓ癌基因相关片段,分别采用２％琼脂糖凝胶电泳和限制性片段长度多态性分析（ＲＦＬＰ）检测口腔癌中的ＨＰＶ１６ＤＮＡ和Ｈａ－ｒａｓ癌基因第１２位密码子的点突变,结果 在１７例口腔癌组中,６     

口腔鳞癌中HPV感染状况与抑癌基因P53突变关系的研究

采用多聚酶链反应技术扩增３０例福尔马林固定石蜡包埋的口腔鳞癌组织中的ＨＰＶ ＤＮＡ及Ｐ５３第七外显子基因，结果显示ＨＰＶ ＤＮＡ阳性者２２例，Ｐ５３基因有突变者１６例。其中ＨＰＶ ＤＮＡ阳性者约有１／２存在着Ｐ５３基因突变，ＨＰＶ ＤＮＡ阴性者绝大部分在Ｐ５３突变。本研究表明Ｐ５３基因突变在ＨＰＶ ＤＮＡ阴性的鳞癌的癌发生中发挥了重要作用，而在ＨＰＶ ＤＮＡ阳性的鳞癌中Ｐ５３基因突变只是鳞癌发生中     

口腔鳞癌中人乳头瘤病毒的研究

为了探讨人乳头瘤病毒（ｈｕｍａｎｐａｐｉｌｏｍａｖｉｒｕｓ，ＨＰＶ）１６、１８型及其与癌的关系，作者采用聚合酶链反应（ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ，ＰＣＲ）技术，检测２３例口腔鳞状细胞癌（ｏｒａｌｓｑｕａｍｏｕｓｃｅｌｃａｒｃｉｎｏｍａ，ＯＳＣＣ），正常口腔粘膜（ｎｏｒｍａｌｏｒａｌｍｕｃｏｓａ，ＮＯＭ）中的ＨＰＶ１６型和１８型ＤＮＡ中的Ｅ６、Ｅ７基因片段，并对其ＰＣＲ产物进行Ｓｏｕｔｈｅｒｎ印迹杂交分析，以研究ＨＰＶ与ＯＳＣＣ的关系。结果显示：ＯＳＣＣ中ＨＰＶＤＮＡ阳性率４７．８％（１１／２３），其中ＨＰＶ１６型６例，ＨＰＶ８型３例，ＨＰＶ１６和１８型复合感染２例，ＮＯＭ中ＨＰＶ阳性率２０％（２／１０），２例阳性者，均为ＨＰＶ１６型。研究结果提示：高危型ＨＰＶ与口腔鳞癌可能有关，二者的确切关系尚需进一步研究。但ＨＰＶ致癌基因Ｅ６、Ｅ７片段在口腔鳞癌中的检出，为鳞癌的病因研究开辟了新的前景     

口腔粘膜组织中HPV16DNA和空泡细胞关系的研究

本研究采用斑点杂交技术，检测８３例口腔扁平苔藓、口腔白斑、口腔鳞癌及正常口腔粘膜组织中的ＨＰＶ１６ ＤＮＡ，并分析ＨＰＶ１６ ＤＮＡ与空泡细胞出现的关系。口腔粘膜组织ＨＰＶ１６ ＤＮＡ的检出率为１０．８％，空泡细胞的检出率为３４．９％。两者均阳性的检出率为７．２％，结果提示空泡细胞不是ＨＰＶ感染所特有的，不能作为诊断ＨＰＶ的特征性指标。     

谷胱苷肽S转移酶在口腔白斑和口腔鳞癌中的表达

目的：对不同增生程度的口腔白斑和鳞癌中ＧＳＴ－π的表达进行研究。方法：用免疫组化ＡＢＣ法,对单纯增生,轻、中度异常增生,重度异常增生和口腔鳞癌患者的组织病理切片,进行免疫组化染色。结果：口腔白斑和口腔鳞癌组织中均有ＧＳＴ－π表达,且随着白斑异常增生程度增高,其表达逐渐增高,其表达程度与白斑异常增生程度有关,在鳞癌组织中表达最高。结论：ＧＳＴ－π可作为口腔白斑和口腔癌的标志物,可对口腔白斑和口腔癌的     

Unusual HPV types in oral warts in association with HIV infection

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesions, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV). In this study, oral warts in 17 HIV-seropositive individuals were biopsied. Southern blot analyses were performed and the HPV types found were HPV 7 (7/17), 13 (1/17), 32 (1/17), and 18 (1/17). The presence of HPV type 7 is unusual in that it normally is found only in butcher's warts. There was no correlation between HPV type, histopathology, and clinical appearance of the lesions examined, except that the flat (FEH type) warts contained HPV types 13, 18 and 32 (1 of each). HIV infection appears to predispose individuals to oral infection with unusual HPV types.     

人乳头状瘤病毒感染与儿童口腔黏膜良性上皮增生

目的 探讨儿童口腔黏膜良性上皮增生性病损与人乳头状瘤病毒(human papillomavirus，HPV)感染及其类型的关系。方法 选取四川大学华西口腔医学院病理科近10年30例儿童口腔黏膜良性上皮增生性病损的病例，复习其临床病理特征及切片，并采用免疫组织化学及原位杂交方法检测HPV共同抗原及其类型。结果 口腔鳞状细胞乳头状瘤(squamous cell papilloma，SCP)20例(66．7％)，尖锐湿疣(condyloma acuminatum，CA)6例(20．0％)，口腔黏膜局灶性上皮增生(focal epithelial hyperplasia，FEH)4例(13．3％)。HPV检测结果显示：HPV共同抗原阳性者占73．3％(22／30)，其中SCP占75．0％(15／20)，6例CA HPV共同抗原均为阳性，4例FEH中仅1例HPV共同抗原为阳性；HPV类型以高危型HPV16／18为主，占77．3％(17／22)，其次是HPV6和HPV11。结论 儿童口腔黏膜良性上皮增生性病损与HPV感染关系密切，病毒类型以高危型HPV16／18为主，其病毒类型是否与成人(以HPV6、11为主)不同尚待进一步研究。     

Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16

Proliferative verrucous leukoplakia (PVL) is a recently described clinical entity characterized by multifocal oral lesions that frequently progress to oral cancer despite abstinence from tobacco use by most patients. To determine if this condition is associated with human papillomavirus (HPV), a polymerase chain reaction (PCR) for HPV DNA was performed on 9 lesions from 7 patients with PVL, histologically diagnosed with focal keratosis (1), papilloma (1), epithelial dysplasia (5) and squamous cell cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For comparison, we studied 55 non-PVL-associated oral specimens, including 24 oral squamous cell cancers. Of the cancers, 8 (33%) were HPV positive, 4 for HPV 16. These data suggest that HPV 16 infection may play an important role in the pathogenesis of PVL-associated oral dysplasia and possibly cancer, but is found in only a small proportion of the more common, non-PVL associated-oral lesions.     

Condyloma acuminatum and human papilloma virus infection in the oral mucosa of children

PURPOSE: The purpose of this study was to investigate the clinicopathological features of oral condylomas in children and condylomatous lesions of their mothers. Moreover, the authors sought to determine the mode of transmission of this disease and to find the genotype of human papilloma virus (HPV) in the children's oral condyloma. METHODS: Nine instances of oral condyloma acuminatum in children and lesions in their mothers were reviewed. Their HPV genotypes were evaluated by in situ hybridization (ISH). RESULTS: This study revealed that the lesions appeared during 3 years of age and the most common location was the hard and soft palate. Seven of the 9 mothers had experienced vulva and/or oral cavity condylomata during pregnancy. Social evaluation confirmed sexual abuse in 1 girl, and probable sexual abuse in another girl. The results of ISH demonstrated HPV 16/18 DNA being positive in 5 of the 9 cases, and HPV 6 and HPV 11, HPV 6 and HPV 16/18, HPV 6, and HPV 11 DNA being positive, respectively, in 1 case. HPV DNA types in mother-child pairs were not concordant. CONCLUSIONS: Oral condyloma acuminatum in children is probably induced by HPV 16/18. The mode of transmission by sexual abuse is the most likely route. Prenatal transmission of HPV to children is rare. This study provides further confirmation of possible different genotype and transmission in oral CA of children and adults.     

Unusual HPV types in oral warts in association with HIV infection

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesiona, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV). In this study, oral warts in 17 HIV-seropositive individuals were biopsied. Southern blot analyses were performed and the HPV types found were HPV 7 (7/17), 13 (1/17), 32 (1/17), and 18 (1/17). The presence of HPV type 7 is unusual in that it normally is found only in butcher's warrs. There was no correlation between HPV type, histopathology, and clinical appearance of the lesions examined, except that the flat (FEH type) warts contained HPV types 13, 18 and 32 (1 of each). HIV infection appears to predispose individuals to oral infection with unusual HPV types.     

Detection of human papillomavirus DNA in oral mucosal lesions using in situ DNA-hybridization applied on paraffin sections

The in situ DNA hybridization technique, carried out under stringent conditions, was used to detect human papillomavirus (HPV) DNA of types 6, 11, and 16 in paraffin sections of 32 surgically treated oral mucosal lesions. Expression of HPV structural proteins was analyzed by means of the immunoperoxidase (IP-PAP) method. A total of 10 (31.3%) of the 32 lesions proved to express HPV antigens, which were found in 4 of 7 squamous cell papillomas, in 2 of 2 classic condylomas, in 2 of 10 papillary hyperplasias, and in 2 of 3 leukoplakia lesions. Two of the squamous cell papillomas contained HPV 6 DNA, and 4 additional lesions were positive for HPV 11 DNA. In one of the condylomas, a double infection by HPV 6 and 11 was found, while the second was positive for HPV 11 alone. Both the HPV antigen-positive papillary hyperplasias contained HPV 6 DNA, as did the HPV antigen-positive leukoplakia lesions. Of the latter, one was infected by HPV 6 and 11. DNA of the "high-risk" HPV 16 was contained in two lesions: one lichen planus lesion and one of the two squamous cell carcinomas. The results confirm the previously reported evidence of HPV involvement in oral mucosal lesions. The implications of these findings are discussed in terms of the well-established premalignant character of oral leukoplakia and oral lichen planus, although far less commonly versus leukoplakia, with special emphasis on the discovery of the "high-risk" HPV 16 in the latter as well as in oral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prevalence and distribution of human papillomavirus genotypes in oral epithelial hyperplasia: proposal of a concept

Background:  Evidence is accumulating for the aetiological role of human papillomavirus (HPV) in the pathogenesis of potentially malignant oral mucosal lesions and squamous cell carcinomas.
Methods:  Paraffin tissue sections from 49 patients with 'white patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH).
Results:  Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ≥ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed.
Conclusions:  The high prevalence of HPV infection in hyperplastic 'white patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions – flat, exophytic, wart-like or papillary proliferations – could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis.     

Biopsy vs. superficial scraping: detection of human papillomavirus 6, 11, 16, and 18 in potentially malignant and malignant oral lesions

BACKGROUND: Several epidemiologic studies have shown a broad variation in the prevalence of human papillomavirus (HPV) in oral precancerous tissues and oral carcinomas. METHODS: Biopsies and superficial scrapes of lesions, clinically suspected of HPV infection, were taken from patients with potentially malignant and malignant oral lesions, and subject to HPV DNA detection by PCR-Southern blot analysis. RESULTS: From 22 patients with potentially malignant and malignant lesions analyzed, 41% of the biopsies were HPV DNA positive, whereas 95-100% of the superficial scrapes were positive (McNemar, P < 0.0001). Clinical presumption of HPV infection detected 67% (P < 0.0001) of the HPV DNA positive cases compared with 48% (P < 0.0001) determined by cytology and histopathology. The prevalence of HPV 6, 11, 16 and 18 in the oral mucosa was studied in 59 individuals. While 9% of normal controls were HPV DNA positive, 100% of the patients with potentially malignant and malignant lesions were HPV DNA positive, and the prevailing genotype was HPV 16 followed by HPV 18. CONCLUSIONS: The higher HPV DNA detection rate in superficial oral scrapes than in biopsies suggests that accurate epidemiological information on oral HPV infection/oral carcinogenesis depends not only on the DNA detection technique, but also on the tissue/cell sampling procedure.     

艾滋病感染者口腔疣状肿块人类乳头状瘤病毒感染与P53,Ki-67蛋白过度表达

目的 :了解艾滋病感染者口腔黏膜疣状肿块细胞生物学特性。方法 :应用免疫组织化学法、PCR对艾滋病感染者口腔黏膜疣状肿块、非艾滋病感染者口腔黏膜癌前病变和鳞癌组织中P5 3和Ki 67蛋白、人类乳头状瘤病毒 (HPV ) ,巨细胞病毒 (CMV)和EB病毒 (EBV )进行检测。结果 :( 1)艾滋病感染者口腔黏膜疣状肿块中P5 3蛋白阳性表达率为 2 3 % ,Ki 67蛋白阳性表达率为 76% ,二者均低于非艾滋病感染者口腔黏膜鳞癌(P <0 .0 5 ) ,但与非艾滋病感染者口腔黏膜癌前病变无明显差别 (P >0 .0 5 ) ;( 2 )艾滋病感染者口腔黏膜疣状肿块中 ,HPV感染率为 88.2 % ,明显高与非艾滋病感染者口腔黏膜癌前病变和口腔黏膜鳞癌 (P <0 .0 1)。没有检测到EBV、CMV病毒感染。结论 :艾滋病感染者口腔疣状肿块和HPV感染有关 ,存在抑癌基因突变和细胞过度增殖现象。