Risk Factor For Oral Carcinogenesis Research Articles

Heterogeneity: A stumbling block in the expression of human papillomaviruses 16 in oral squamous cell carcinoma

Background: Tobacco and smoking are the established risk factors for oral cancer, but studies have reported the occurrence of oral cancer, even in the absence of these established factors. This indicates the need to identify other possible risk factors. In recent years, viral carcinogens have gained interest in which human papillomaviruses (HPVs) are the most researched risk factor in oral carcinogenesis. Therefore, we conducted this study to evaluate the presence of HPV-16 in potentially malignant and malignant lesions of the oral cavity. Methods: The current study comprised 40 patients, and they were divided into two groups: Group A: 20 patients with histopathologically diagnosed oral potentially malignant disorders (leukoplakia/erythroplakia) and Group B: 20 patients with histopathologically diagnosed oral squamous cell carcinoma (OSCC). Tissue samples were collected from all patients and made into formalin-fixed paraffin-embedded (FFPE) blocks. Polymerase chain reaction (PCR) test was carried out to detect the presence of HPV-16. Results: In our study, we found that none of the FFPE tissue samples was positive for the HPV-16 genome using the conventional PCR technique. The level of significance (P value) was set at P

Role of human papilloma virus infection and oral-genital contact in oral cancer ethiopathogenesis

Head and neck squamous cell carcinoma and especially oropharyngeal squamous cell carcinoma is a very significant cause of morbidity and mortality. The majors risk factors of these tumors are tobacco smoking, chewing and alcohol consumption. But there is a group, non-drinking and non-smoking, patients with oropharyngeal squamous cell carcinoma. In these patients may be oral-genital contact and human papillomavirus infection the major risk factor for oral carcinogenesis. Aim of this review is to point out this fact in correlation with clinical studies and clinical conclusion for medical practice (Fig. 1, Ref. 32).

Cigarette smoke condensate promotes pro‐tumourigenic stromal–epithelial interactions by suppressing miR‐145

Exposure to factors released from tobacco during chewing or smoking is recognized as a major risk factor for oral carcinogenesis and influences the phenotype of oral epithelial cells and fibroblasts within the underlying stroma. Micro(mi)RNA can regulate the expression of genes within cells, and previous studies show that tobacco products can alter the miRNA profiles in lung epithelial cells. However, the molecular alterations occurring in oral fibroblasts exposed to tobacco constituents remain to be elucidated. Oral fibroblasts were exposed to cigarette smoke condensate (CSC) and miRNA expression compared to untreated controls using tiling low-density arrays (TLDA). Expression of miRNA-145 was confirmed by quantitative (q)RT-PCR. The effect of CSC on fibroblast cell viability, motility and matrix metalloproteinase (MMP)-2 expression was measured using MTS, a wound scratch assay and qRT-PCR, respectively. Oral cancer cell migration in response to culture supernatants from mock, control or pre-miR-145-transfected CSC-treated fibroblasts was analysed by chemotaxis assay. TLDA analysis identified widespread changes in the miRNA expression profile of fibroblasts exposed to CSC. Pri-, pre- and mature miRNA-145 were significantly down-regulated in response to CSC, and this was accompanied by up-regulated expression of MMP-2 and increased migration of fibroblasts compared to untreated controls. Re-expression of miR-145 abrogated the ability of fibroblasts to promote oral cancer cell chemotaxis in response to CSC. These findings suggest that tobacco constituents influence the expression of miRNA within oral fibroblasts promoting a phenotype that increases oral cancer migration and sheds new light on the mechanisms underlying oral cancer pathogenesis.

Detection of Human Papillomavirus DNA in Intraosseus Ameloblastoma*

Human Papillomavirus (HPV) infection has been shown as a risk factor in oral carcinogenesis. The association between HPV and benign and malignant neoplasm of oral mucosa, especially surface epithelium-derived tumors, is well established. The role of HPV in pathogenesis of odontogenic cysts and tumors has been published in few articles. The aim of this study was detection of HPV in Iranian patients with intrabony ameloblastoma and investigation of specific risk factors associated with ameloblastoma. One hundred intrabony ameloblastoma and 50 age-sex matched samples as controls were evaluated by polymerase chain reaction for the detection and typing of HPV. Fisher exact and chi square tests were used to assess the data. HPV DNA was detected in 32% of patients and 10% of controls. HPV-6 was the most prevalent genotype (31.6%) in infected cases. It was followed by HPV-11 (12.5%), HPV-16 (12.5%) and HPV-31 (3.1%). We found a significant association between presence of HPV and location of tumor (p = 0.02), traumatic history (p = 0.03) and ododontic therapy (p = 0.01). These findings indicated that HPV-6 probably is one of the most important etiologic agents in causing intraosseous ameloblastoma in Iranian population. © 2006 Academic Journals Inc., USA.

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

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). 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. 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. 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.

Correlation between c-Jun and human papillomavirus in oral premalignant and malignant lesions

c-Jun, one of the components of the transcription factor activating protein-1 (AP-1), is suggested as a factor in malignant progression of oral lesions. c-Jun and other AP-1 components relationships with human papillomavirus (HPV) infection have been investigated, but not yet focusing on oral carcinogenesis. The aim of this study was to verify whether c-Jun immunohistochemical expression is related to HPV DNA detection in oral premalignant and malignant lesions. Fifty cases diagnosed as oral leukoplakias, with different degrees of epithelial dysplasia, and as oral squamous cell carcinomas (OSCC) were submitted to immunohistochemistry to detect c-Jun and to in situ hybridization with signal amplification to assess HPV DNA. It was verified that c-Jun nuclear expression increased according to the degree of dysplasia within the lesion, with the greatest expression in OSCC. The same did not happen concerning HPV infection--a discrete proportional relation was observed in indexes found in leukoplakia with no dysplasia, leukoplakia with dysplasia and OSCC, but statistically insignificant. When separating the group of leukoplakia by degrees of dysplasia, this relation of proportion was not observed. Nevertheless, the overall prevalence of HPV infection was 24% and the high-risk HPV types were the most frequently identified, which does not allow excluding HPV as a risk factor in oral carcinogenesis. When relating c-Jun expression and HPV infection, no statistically significant relationship is observed. Results suggest then that malignant progression mediated by c-Jun is independent of the presence of HPV in oral carcinogenesis.

Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis.

Matrix metalloproteinase-2 (MMP-2) can degrade extracellular matrix and basement membrane, and play an important role in the development and progression of multiple carcinomas, including oral squamous cell carcinoma (OSCC). A -1306C-->T polymorphism in the MMP-2 promoter disrupts Sp1-binding site, and results in reduction of transcriptional activity. This study aimed to assess the association of such genotype with the risk of OSCC and oral submucous fibrosis (OSF), which is a precancerous condition that exhibits excessive collagen production and etiologically links to areca use. Genomic DNA from the blood samples of 121 OSCC cases, 58 OSF cases and 147 controls were amplified by polymerase chain reaction (PCR) and subjected to denaturing high-performance liquid chromatography (dHPLC) analysis for genotyping. The OSCC were further classified into buccal squamous cell carcinoma (BSCC) and non-buccal squamous cell carcinoma (NBSCC), according to the site of involvement. Fisher's exact test and unconditional logistic regression models were used for statistical analysis. Subjects carrying CC genotype had nearly twofold increased risk for developing OSCC when comparing with CT or TT genotype. Subjects carrying CC genotype had more apparent risk (greater than fourfold) for developing NBSCC. However, no increase in risk for lymph node metastasis or advanced stage was identified in OSCC cases carrying such genotype. Preliminarily data suggest no significant association between subjects carrying CC genotype and the development of BSCC or OSF. This is the first paper demonstrating that functional genotype of MMP-2 promoter is a risk factor for oral carcinogenesis, particularly for the subsets occurring on non-buccal site.

Presence of human papillomavirus in malignant oral lesions

The purpose of this study was to investigate the prevalence of human papillomavirus 6/11 and 16/18 in patients, with oral lesions clinically diagnosed as leucoplakia, attending the School of Dentistry, University of São Paulo State/UNESP, Brazil. After paraffin embedded process, in the sections staining with H&E, 30 biopsies were screened and separated on 3 groups: 10 oral lesions without dysplasia, 10 with dysplasia, and 10 with invasive squamous cell carcinoma. The lesions with dysplasia were classified in agreement with Van Der Wall's histopathological standard method. Oral lesions were investigated for the presence of human papillomavirus (HPV) by in situ hybridization with wide-spectrum, 6/11 and 16/18 biotinylated probes. HPV 16/18 was found in 20% (n = 2) of the leucoplakia with severe-degree dysplasia. The presence of HPV 16/18 in malignant lesions suggests its importance as a risk factor for oral carcinogenesis.

P53 polymorphism, human papillomavirus infection in the oral cavity, and oral cancer.

Human papillomavirus (HPV) infection has emerged as a risk factor in oral carcinogenesis. An arginine-coding polymorphism of the tumor suppressor protein p53 at codon 72 is more readily degraded by the HPV oncoprotein E6. Our objective was to evaluate the association between p53 polymorphism at codon 72 and HPV infection in the oral cavity, as well as its association with oral cancer. Oral squamous cells from 202 patients with oral cancer and 333 age-sex frequency matched controls were evaluated by polymerase chain reaction for the presence and type of HPV and for alleles of codon 72 in p53. Fisher exact test and chi(2) tests were used to evaluate the data. The p53 codon 72 polymorphism is not associated with HPV infection, whether comparing HPV-negative controls with HPV-positive controls or comparing HPV-negative cases with HPV-positive cases. Additionally, we found no association with the codon 72 polymorphism and oral cancer, whether comparing HPV-negative controls with HPV-negative cases or comparing HPV-positive controls with HPV-positive cases. There is no association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.