Human Papilloma Virus, Epstein-Barr Virus, and Herpes Simplex Virus Type-1 in Oral Squamous Cell Carcinomas from Three Populations
Abstract: Most oral squamous cell carcinoma (OSCC) is believed to develop via a multistep process of cumulative gene damage in epithelial cells. Increasing incidence of OSCC and evidence that traditional risk factors may not be responsible directed us to investigate the prevalence of virus in pre- and malignant samples.The integration of the DNA from human papillomavirus (HPV), Epstein-Barr virus (EBV), and Herpes simplex (HSV) into the human genome is associated with the expression of oncogenes and the down-regulation of tumor-suppressor genes in OSCC carcinogenesis. This thesis compared samples from India and Sudan, two countries on two continents having a documented high incidence of oral cancer, with specimens from Sweden, with its known low incidence of oral cancer. Each region has, in addition to smoking, a unique non-smoked tobacco habits with documented carcinogenic effects. These countries also typify areas of low and high socioeconomic living conditions with their expected impact on disease development. The study populations were selected from tobacco users and nonusers with OSCC, oral sub-mucous fibrosis (India), oral lichen planus (Sweden), oral leukoplakia with and without dysplasia and snuff-induced lesions (Sweden and Sudan). An expedient method was developed for extracting DNA from old formalin-fixed and paraffin-embedded biopsies. The prevalence of HPV, EBV, and HSV was investigated using PCR/DNA sequencing and southern blot hybridization analysis. We found HPV and EBV to be most prevalent in samples of tissue characterized as normal, with decreasing prevalence in dysplastic and malignant lesions. This intriguing finding that prevalence decreases as neoplastic development proceeds warrants further investigation. Our data do not at first sight support the conclusion that viruses and tobacco use jointly interact with cell mechanisms in the development of oral cancer.
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