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)、疱疹病毒Ⅰ型(HSV-Ⅰ)和人巨细胞病毒(HCMV)的关系.方法:采用斑点杂交和PCR技术检测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-Ⅰ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、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)、疱疹病毒I型 (HSV -I)和人巨细胞病毒 (HCMV)的关系。方法 :采用斑点杂交和PCR技术检测 32例口腔鳞癌、14例口腔白斑和 10例正常口腔粘膜中HPV1 6 、HSV -I及HCMVDNA。结果 :在正常口腔粘膜、白斑及口腔鳞癌中HPV16、HSV -I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HPV1 6 -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 :HPV1 6 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HPV1 6 有协同致癌的作用。     

口腔鳞癌组织中人乳头瘤病毒16型的原位杂交研究

目的：探讨HPV16-E6基因在口腔粘膜白斑，口腔鳞状细胞癌组织中的表达及其在口腔鳞癌发生、发展过程中的意义及分布特征。方法：应用地高辛标记的HPV16-E6的寡核酸探针分别对口腔鳞状细胞癌组织，口腔粘膜白斑组织，宫颈癌组织及正常组织中进行原位杂交，以检测各组织中HPV16型的DNA表达和分布情况，结果：口腔鳞状细胞癌组织HPV16阳性率46．67％；口腔粘膜白斑组织阳性率60％。HPV16E6基因阳性信号集中分布于癌细胞胞核中。结论：原位杂交方法可用来检测OSCC组织中HPV16型DNA的存在并能准确组织定位；较高的阳性率进一步支持高危型HPV16型的感染与口腔鳞状细胞癌的发生有关；在癌前病损组织中的高危型HPV16的检m率高于口腔鳞癌组织，说明HPV在口腔鳞癌发生的早期阶段可能具有致癌作用。     

人乳头状瘤病毒16/18型在口腔疣状癌中的表达及意义

目的　研究人乳头状瘤病毒 16 /18型在口腔疣状癌中的表达状况 ,探讨其在口腔疣状癌发生发展中的生物学意义。方法　采用SP免疫组化和原位杂交方法分别检测 8例正常口腔粘膜、13例疣状癌、10例高分化鳞状细胞癌、10例低分化鳞癌组织中HPV16 /18E6蛋白和HPV16 /18DNA的表达。结果　①疣状癌HPV16 /18E6蛋白及HPV16 /18DNA阳性表达率均为 6 9.2 % (9/13) ,E6蛋白平均染色强度高于高分化鳞状细胞癌和低分化鳞状细胞癌组 (P <0 .0 5 )。②免疫组化方法检测HPV16 /18E6蛋白与原位杂交方法检测HPV16 /18DNA结果有良好的一致性。结论　HPV16 /18型感染是口腔疣状癌的重要致病因子 ,与高分化鳞状细胞癌、低分化鳞状细胞癌组织相比 ,HPV16 /18型感染与疣状癌的关系更为密切。     

口腔鳞状细胞癌中人乳头瘤病毒感染的检测

目的检测人乳头瘤病毒(HPV)在口腔鳞状细胞癌中感染及其与口腔癌发生的相关性.方法采用PCR方法,检测30例口腔鳞状细胞癌及5例正常口腔黏膜中HPV 16和18感染.结果 7/30例标本中检测出HPV 16(23.3%);10/30例标本中检测出HPV 18(33.3%).3/30例标本中存在HPV 16和18共感染(10%).5例正常口腔黏膜中未发现HPV 16和HPV 18感染.在检测HPV 16时发现一条新片断(186 nt),经测序此序列与人5号染色体的核酸序列65-175存在99%同源.结论 HPV 16和18可能与口腔鳞状细胞癌的发生密切相关.     

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。     

复发性阿弗它溃疡患者脱落细胞中人巨细胞病毒的检测及意义

本研究采用PCR技术，分别对28例溃疡期RAU患者和28例正常人口腔脱落细胞中HCMVDNA进行检测。RAU患者中HCMVDNA阳性率为39．29％，正常对照组为3．57％，二者比较，差异有极显著意义（P＜0．005）。RAU．＠者溃疡区脱落细胞及正常粘膜均存在HCMVDNA，其中溃疡区阳性率为28．57％，正常粘膜为17．86％，二者差异无显著性（P＞0．05）。HCMVDNA的检测为HCMV在RAU患者口腔粘膜局部的存在提供了直接依据。结果提示，HCMV是RAU的病原之一。     

口腔鳞状细胞癌高危型人乳头状瘤病毒感染的检测

目的 观察口腔鳞癌及口腔粘膜高危型人乳头状瘤病毒（HPV）感染情况,探讨HPV感染与临床及病理资料的关系。方法 用多聚酶链反应（PCR）检测73例口腔鳞癌及40例正常口腔粘膜石蜡包埋组织中HPV16、HPV18的DNA。统计分析其与临床及病理资料的关系。结果 口腔鳞癌HPV16／HPV18 DNA阳性率为74％（54／73）,正常口腔粘膜为55％（22／40）。口腔鳞癌与正常口腔粘膜HPV阳性率存在显著性差异（P＝0．040）。统计分析显示：HPV感染与患者的性别、年龄有关,与其它因素（肋瘤发生部位、嗜烟酒情况、肿瘤病理分级、临床分期）无关。结论 高危型HPV感染与口腔鳞癌的发生有关。口腔粘膜中HPV感染普遍存在,提示HPV在口腔肿瘤的发生中并非独立发挥作用。     

人乳头瘤病毒与口腔肿瘤及其16E5基因

人乳头瘤病毒（HPV）是一种小型无包膜的双链环状DNA肿瘤病毒,根据其伴随上皮损伤的恶性程度分为低危型和高危型,高危型HPV持续感染是口腔鳞状细胞癌（OSCC）形成的最重要因素,75%的OSCC中可检测到高危型HPV16。HPV16全长基因组分为早期区（E区）、晚期区及非编码调节区,其中E区包括8个开放阅读框,即E1~E8。HPV16E5基因引起细胞融合并形成双核细胞,是恶性肿瘤发生的征兆。表皮生长因子受体（EGFR）是HPV16E5蛋白作用机制中的关键部分,控制细胞的生长和增殖进程。肿瘤细胞中存在着EGFR过表达现象,一些抗癌药物抑制EGFR表达可起到治疗肿瘤的作用。环加氧酶（COX）2是一种可在人体中促进细胞增殖、抑制程序性细胞死亡和促进血管形成的酶,HPV16E5蛋白与EGFR协同诱导COX2表达,共同参与肿瘤的恶性转化进程。本文就HPV与口腔肿瘤、HPV16E5基因的功能等研究进展作一综述。     

HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic

OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of development of a subgroup of head and neck cancers has been proposed recently. The main risk factors of oral and oropharyngal cancer observed in our population are smoking and alcohol consumption. The incidence of oral/oropharyngeal tumours in the Czech Republic is relatively high and there are no data available about the prevalence of HPV DNA presence in these tumours. MATERIALS AND METHODS: Eighty patients with a primary oropharyngeal cancer were enrolled. The presence of HPV DNA has been evaluated by polymerase chain reaction in 68 cases from which the tumour tissue and demographical and clinical data were available. The typing of HPV was performed by nucleotide DNA sequencing. RESULTS: The HPV DNA was detected in 51.5% of samples tested. Among the HPV DNA positive tumours, 80% contained HPV16. In the analysed group there were 54 men and 14 women. The prevalence of HPV DNA was lower in oral (25%) than in oropharyngeal (57%) tumours, and higher in never smokers (100%) and never drinkers (68.8%). HPV DNA presence was not related to gender, age, number of lifetime sexual partners or practice of oral-genital sex, size of tumour or presence of regional metastases. CONCLUSIONS: The difference in the prevalence of HPV DNA positive tumours between cases of oral cavity and oropharyngeal carcinoma exposed and not exposed to tobacco or alcohol support the theory that HPV DNA positive tumours form an aetiologically distinct subgroup of head and neck tumours.     

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。     

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.     

Human papillomavirus as a risk factor in oral carcinogenesis: a study using in situ hybridization with signal amplification

Introduction:  It is still controversial whether human papillomavirus (HPV) can be considered a risk factor in oral carcinogenesis. The aim of this study was to detect HPV DNA in 50 cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas, using in situ hybridization with signal amplification (CSA-ISH).
Methods:  HPV DNA was assessed in paraffin sections using CSA-ISH with a wide-spectrum biotinylated DNA probe. In HPV-positive cases, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed.
Results:  The overall prevalence of HPV infection was 24%, markedly higher than that found in the control group. Results showed a discrete proportional relationship in the indices found in leukoplakia with no dysplasia, leukoplakia with dysplasia, and squamous cell carcinoma, but this was not statistically significant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. In genotyping, HPV types 16/18 were the most prevalent, and types 6/11 were only found in groups of mild or no dysplasia.
Conclusion:  The results suggest that HPV is not likely to play a role in the progression of malignant transformation in oral lesions. Nevertheless, the increased prevalence of HPV infection compared to normal oral mucosa and the fact that high-risk HPV types were the most frequently identified do not allow the exclusion of HPV as a risk factor in oral carcinogenesis.     

Comparative study of HPV prevalence in Japanese and North-east Chinese oral carcinoma

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of oral carcinoma. However, the reported prevalence of HPV in oral carcinoma has varied widely. METHODS: The prevalence of HPV 16, 18 and 33 was investigated in Japanese and North-east Chinese oral squamous cell carcinomas (OSCCs) with polymerase chain reaction (PCR). The expression of p53 protein was examined immunohistochemically. RESULTS: HPV 16 and 18 were detected in 7 (23.3%) and 10 (33.3%) of 30 Japanese and 11 (36.7%) and 5 (16.7%) of 30 Chinese samples, respectively. HPV 16 and 18 coinfection was detected in 3/30 Japanese and 2/30 Chinese samples. HPV 33 was not detected. There was no significant correlation between HPV 16 and 18 and the sites, gender, age and histological grade. The prevalence of both HPV 16 and 18 was similar and higher in the Japanese and North-east Chinese samples (46.7% each). HPV 16 or/and 18 infection or/and p53 overexpression were in 22 (73.3%) of 30 Japanese samples and 24 (80.0%) of 30 North-east Chinese samples, respectively. CONCLUSIONS: HPV 16/18 infection or/and p53 overexpression may play an important role in developing some OSCCs. and the presence of HPV sequences and mutant p53 are not necessarily mutually exclusive.     

Detection of human papilloma virus type 16 DNA in oral squames from normal young adults

We have employed the polymerase chain reaction (PCR) to detect Human Papillomavirus (HPV) type 16 in oral squames and mononuclear cells from 62 healthy young adult volunteers. Two groups were screened for the presence of this virus, but in not all cases was DNA obtained from the scrapes. In the first (n = 30), the results show that 43% of normal individuals harbour HPV 16 (a genital type) in their buccal mucosa, epithelium of dorsum of tongue and hard palate. In the second group (n = 18), 44% of individuals were positive for HPV 16 in their oral epithelial scrapes, while only 6% were positive for the same virus in mononuclear cells. Interestingly, in 2 cases, peripheral blood lymphocyte DNA gave a positive reaction with the HPV 16 primers. To investigate possible HPV infection of lymphocytes, a further 42 lymphocyte samples, taken from the same age group as the epithelial study group, were analysed. None of these lymphocytes were positive for the presence of HPV 16 DNA.     

Use of quantum dots to detect human papillomavirus in oral squamous cell carcinoma

Objective:  To examine the association of oral squamous cell carcinoma with human papillomavirus (HPV) using quantum dots (QD) in situ hybridization (ISH).
Methods:  Expression of HPV16/18 was analyzed in a representative collection of 21 oral squamous cell carcinomas by tissue microarrays. The presence of HPV16/18 high risk was detected by applying QDISH which is compared with conventional ISH.
Results:  Seven cases out of 21 (33.3%) were positive for QDISH while 1 out of 21 (4.8%) was positive for ISH, although all of HPV DNA were localized in the nuclei in the spinous and basal cell layer of the epithelium. The difference between these two methods was significant ( P  < 0.05).
Conclusions:  These results demonstrate that the QD might be an efficient method for determination of HPV infection and HPV-associated oral squamous cell carcinoma.     

Comparative study of oral squamous cell carcinoma in Okinawa, Southern Japan and Sapporo in Hokkaido, Northern Japan; with special reference to human papillomavirus and Epstein-Barr virus infection

In Okinawa, a subtropical island in Southern Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that in mainland Japan. Sixty cases of oral squamous cell carcinoma from 1993 to 1996 in Okinawa and 42 cases over the same period in Sapporo were examined histologically. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) were detected by polymerase chain reaction (PCR) amplification with primers specific for HPV and EBV. In situ hybridisations of the viruses were also carried out. In the case of Epstein-Barr virus, in situ PCR was also performed. Thirty-five (58.3%) Okinawan tumours were well-differentiated in type, but in Sapporo, 18 (42%) were of such type. In Okinawa, tumours of the mouth floor (10 cases, 16.7%) and oropharynx (12 cases, 20%) were frequently observed, whereas in Sapporo only five cases (12%) of each were found. HPV was demonstrated in 78% of Okinawan cases and 26.2% of Sapporon cases by PCR or non-isotopic in situ hybridisation (NISH). There were 76.6% (46 cases) of Okinawan and 38.1% (16 cases) of Sapporo cases positive for EBV by PCR. In only 12 Okinawan cases and 4 Sapporon cases, were positive signals demonstrated by in situ PCR on the cancer cells themselves. EBV was demonstrated in the large number of infiltrating lymphocytes, most of which were CD3+, and a few were CD19+. In Okinawa, HPV might be an important causative factor of oral squamous cell carcinoma and EBV a less important factor, whereas in Sapporo HPV and EBV might play only a small part in the aetiology of the tumour.