人乳头瘤病毒和人巨细胞病毒与口腔癌的关系

目的：检测口腔白斑和口腔鳞状细胞癌中的人乳头瘤病毒（HPV16）DNA和人巨细胞病毒（HCMV）DNA,探讨HPV16和HCMV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HCMVDNA,采用2%琼脂糖凝胶电泳分析,检测口腔白斑和口腔鳞状细胞癌中的HPV16DNA和HCMVDNA。结果：6例口腔白斑中,HPV16DNA的阳性率为16.7%,HCMVDNA为16.7%,16例口腔鳞癌组织HPV16DNA的阳性率为31.3%,HCMVDNA为25%,例正常组织均未检测出。结论：4HCMV与HPV16在口腔癌的发生中具有协同致癌作用。     

Analysis of human papillomavirus DNA in oral squamous cell carcinomas

Evidence from several laboratories suggests that HPV plays a role in the etiology of squamous cell carcinomas of the oral cavity. A rnultifactorial risk factor profile for the development of oral cancer may include HPV in addition to well-established risk factors such as tobacco and alcohol use. The prevalence of oral carcinomas repotted to be associated with HPV has varied widely due to differences in the sensitivity of the assay used for HPV detection. The aims of this study were: (1) to ascertain the prevalence of HPV DNA in oral squamous cell carcinomas using the most sensitive technique available, the polymerase chain reaction; (2) to determine the type of HPV in the tumors; and 3) to correlate the virologic data with other risk factor data obtained from patients' records. Fourteen (78%) of 18 primary tumors, 6 (67%) of 9 normal epithelial tissues from the patients and 5 (100%) of 5 neck metastases were HPV DNA-positive. Of the 14 HPV DNA-positive primary tumors, specific typing revealed HPV 16 in 2, HPV 18 in 2, HPV 16 and IS in 5, HPV 6/11, 16 and 18 in 4, and HPV 6/11 in 1. HPV types in the normal or metaslatic tissue were usually the same as those in the respective primary tumor. There was no significant association between HPV presence and any of 12 factors or patient characteristics studied.     

High prevalence of oral human papillomavirus infection in Fanconi's anemia patients

Oral Diseases 17 , 572–576 Background: Fanconi’s anemia (FA) is a rare recessive genetic disorder characterized by bone marrow failure, developmental and congenital abnormalities, which frequently evolves to aplastic anemia and neoplasias, primarily acute leukemia and head‐neck carcinomas. Risk of malignancies increases after hematopoietic stem cell transplantation (HSCT), and the role of human papillomavirus (HPV) in FA carcinogenesis have been proposed. Objective: To investigate prevalence of oral HPV in FA patients without oral malignant lesions. Materials and methods: After oral examination, 76 subjects without detectable oral malignant lesions were included and classified in four groups: 20 FA submitted to HSCT (I), 22 FA not submitted to HSCT (II), 18 severe aplastic anemia (SAA) submitted to HSCT (III) and 16 healthy subjects (IV). Liquid‐based cytology sampling, HPV screening by polymerase chain reaction and genotyping by reverse hybridization were performed. Results: The HPV detection rates were: group I 35%, group II 27.3%, group III 38% and group IV 6.25%. Prevalence of high risk HPV types, mainly HPV16, was detected. Compared with control group, suggestions for increased likelihood of being HPV infected in SAA (OR = 9.55, 95% CI: 1.01–125.41) and FA patients submitted to HSCT (OR = 8.08, 0.83–72.29) emerged. Conclusion: Patients without oral malignant lesions submitted to HSCT, have high prevalence of oral HPV. HPV screening and close follow up should be considered in these patients.     

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.     

Detection of human papillomavirus DNA in benign oral squamous epithelial lesions in Venezuela

The polymerase chain reaction (PCR) was applied to the detection of human papillomavirus (HPV) infection in biopsies taken from clinically normal oral mucosa of 20 subjects and clinical lesions of 40 patients. PCR for HPV-DNA amplification was performed using consensus primers MYO9/MYO11 and subsequent typing for HPV of high and low oncogenic risk HPV types were identified by restriction enzyme analysis (restriction fragment length polymorphism, RFLP). The HPV viral genome was present in 55% (22/40) of the oral benign lesions (OBL) and in 10% (2/20) of the control samples. In the PCR+ OBL, we observed 90.9% of low oncogenic risk types (HPV-6 -13 and -32) and 9.1% of the samples had a mixed infection with low and high oncogenic types (HPV-6 and -16). In the control samples, we observed one patient with HPV-6 and another with HPV-6 and -16 in the same sample. All of the eight focal epithelial hyperplasia cases were positive for low risk HPV types (88% HPV-13 and 12.5% HPV-32). In conclusion, this study demonstrates a high incidence of HPV in oral benign lesions from Venezuelan patients.     

Factors affecting retention of Cu in the human oral cavity after mouth rinses

Abstract — Retention of Cu in the mouth after rinses with aqueous solutions of CuSC₄ was measured by atomic absorption spectrophotometry. The retained amount of Cu exhibited a linear relationship against the concentration of the rinsing solution in the range tested. Approximately one third of the Cu retained after a 60 s rinse was retained within the first 15 s, and about 75% within 30 s. Retention of Cu was only little affected by the pH of the rinsing solution in the range from 2.0 to 5.7, being reduced by about 50% at pH 9.0. However, variations in cupric ion activity rather than pH per se could explain these effects. A mutual reduction in retention of either metals was seen when Cu and Zn were applied simultaneously.     

Oral sampling and human papillomavirus genotyping in HIV-infected patients

J Oral Pathol Med (2012) 41 : 288–291 Background: Oral human papillomavirus (HPV) is associated with several health complications especially in combination with HIV infections. Screening may be useful, but methodologies and results have varied widely in previous studies. We conducted a pilot study in an HIV‐positive population to evaluate HPV detection in four different oral sample types. Methods: Upon enrollment, an oral‐rinse (OR) sample was collected in 10 ml saline. Additional samples of the buccal mucosa, tonsils, and oral lesion if present were collected with cytology brushes. DNA was extracted using LC‐MagNAPure, and the Linear Array HPV genotyping Assay (Roche) was used for HPV genotyping. Results: In samples from 100 HIV‐positive participants, HPV was detected in 39 (%) of the oral rinses, 13 (%) mucosal and 11 (12.9%) tonsil brushings. Of seven lesion brushings collected, four were HPV positive. All participants with HPV detected in mucosal, tonsil, or lesion brushings were also positive in the OR sample. Among the rinse samples, 27 different genotypes were detected with HPV84 (n = 6), HPV55 (n = 5), and HPV83 (n = 5) being the most common. Multiple infections were detected in 17 samples (range 2–9, mean 1.9 types). As potential cofactors, only receptive oral sex was significantly associated with HPV (P = 0.018, odds ratio 2.9, 95% CI 1.2–6.9). Conclusion: Sampling is a significant factor for oral prevalence studies. Oral rinse provides the best representation for HPV in the oral cavity. To evaluate associated cofactors other than receptive oral sex, larger studies with case–control design are necessary.     

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。     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Low prevalence of human papillomavirus infection in the healthy oral mucosa of a Northern Italian population

J Oral Pathol Med (2012) 41 : 16–20 Background: Oral cancer is the sixth most common malignancy in developed countries, representing almost 3% of malignant tumors. Tobacco use and alcohol consumption are well‐established risk factors. However, the observation that most patients with oral cancer have not been exposed to these risk factors suggests that additional causes may promote oral carcinogenesis. A link has been suggested between human papillomavirus (HPV) and oral cavity cancer but the significance of HPV contribution to oral carcinogenesis as well as the prevalence of HPV infection in normal oral cavity mucosa remains debated. Methods: In this study, the prevalence of oral HPV infection was evaluated in 81 randomly selected Northern Italian subjects with clinically normal oral mucosa using a nested PCR on DNA extracted by oral smears. Results and conclusions: No HPV‐related lesions were detectable in any of the smears analyzed by cytological approach. nPCR identified HPV DNA in only one (1.2%) of the specimens obtained from clinically healthy oral mucosa and subsequent characterization assigned the positive case to HPV type 90. These data suggest that the incidence of HPV infection in the healthy population might be very low and that other risk factors are likely responsible to promote oral carcinogenesis.     

口腔鳞状细胞癌及白斑人乳头瘤病毒16型感染的临床研究

目的:探讨口腔鳞状细胞癌(OSCC)和白斑(LK)患者人乳头瘤病毒16型(HPV-16)感染和临床病理参数之间的相关性。方法:收集30例OSCC和5例LK患者的组织切片,所有病例均经病理学确诊,提取组织DNA,通过巢式PCR检测HPV-16感染情况。结果:HPV-16与TNM分级之间未见相关性,60岁以下女性患者的HPV-16感染率高于60岁以上女性患者(P=0.024),而男性患者未见HPV-16感染和年龄存在相关性(P=0.649)。结论:60岁以下女性OSCC及LK患者中出现较高的HPV-16感染率,提示这可能是新的致癌危险因子。