Human papilloma virus and Epstein-Barr virus in oral tumours and epithelial lesions

Abstract

Oral squamous cell carcinoma (OSCC) is considered a multifactorial disease, where tobacco use and alcohol habits are known risk factors. Other oral epithelial disorders, such as oral lichen planus (OLP) have an unknown aetiology. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) have, under certain circumstances, oncogenic potential. These viruses also have benign clinical manifestations in the oral cavity. Thus, we hypothesised that a combination of viral and chemical exposure is involved in the development of OSCC and other oral epithelial lesions and tumours as well. The aim of the present study was to evaluate the risk of HPV and EBV infection in conjunction with tobacco and alcohol exposure in the development of oral tumours and epithelial lesions. An expedient method was developed for DNA extraction from old formalin-fixed and paraffin-embedded biopsies. HPV and EBV prevalence was investigated with PCR, Southern blot hybridisation and immunohistochemical analysis. The study population consisted of consecutive patients with OSCC, OLP, and oral leukoplakia. Also patients with snuff-induced lesions were studied. A retrospective study on patients with intraosseous ameloblastomas was performed. Increased HPV prevalence (20.8%) was seen in 53 consecutive patients with OSCC, OLP, and oral leukoplakia, but no effect of tobacco and alcohol consumption was seen. None of the patients with snuff-induced lesions was HPV positive. 41% of the ameloblastomas were HPV positive at initial surgery, but this figure increased to 67% after surgical manipulation. 16.3% of the snuff-induced lesions were EBV positive but this was not statistically significant compared to the control patients (4.5%). Increased EBV prevalence was seen in OSCC (37.9%) and in OLP (26.1%) compared to controls. LMP1 immunohistochemistry confirmed that EBV was present in tumour cells and in the epithelium in OLP. No difference in EBV prevalence was seen in control patients with a smoking history compared to control patients with a non-smoking history. Neither tobacco use, alcohol consumption nor age influenced EBV prevalence. The main conclusions were that consumption of snuff and alcohol as well as smoking do not seem to facilitate HPV or EBV infection, either in tumours, epithelial lesions or in healthy oral mucosa. EBV is present in a substantial amount of OSCC and OLP and may be involved in the aetiology in these lesions. HPV infects oral epithelial lesions and tumours, but the infection is probably a late event in the course of these diseases.