Possible Role Of Human Papilloma Virus In Oral Diseases- An Update

摘要

Human papillomaviruses (HPV) has been an area of interest since last two decades because of its potential role in the pathogenesis of malignant tumors. Approximately 35 years ago a role of human papillomaviruses (HPV) in cervical cancer has been postulated. Today it is well established that this very heterogeneous virus family harbours important human carcinogens, causing not only the vast majority of cervical, but also a substantial proportion of other anogenital and head and neck cancers. This review will cover some of the pathogenetic aspects of papillomavirus research; it tries briefly to analyze the present state of linking HPV to human cancers and other oral lesions and will discuss some emerging developments. Introduction HPV infection is known to be a necessary element for the development of cervical cancer in women, and is also a risk factor for the development of anal, penile, and vulvar cancers.1 Recently HPV infections in oral cavity have also been proposed. The oral cavity is lined by a mucous membrane consisting of a stratified squamous epithelium and lamina propria made up of dense connective tissue. The squamous epithelium of the gingiva, hard palate and the dorsum of the tongue is completely keratinized with a superficial horny layer, whereas in the lip, cheek, vestibular fornix, alveolar mucosa, floor of mouth and soft palate, the epithelium is non-keratinized. Thus, the histology of oral mucosa resembles that of the uterine cervix, other lower genital tract or skin, depending on the anatomic site. On the basis of these morphological similarities, one can anticipate the presence of both the mucosal and cutaneous human papilloma virus (HPV) types in different squamous cell lesions of the oral mucosa.2 Such benign oral lesions include squamous cell papilloma (SCP), condyloma, verruca and focal epithelial hyperplasia (FEH), leukolplakia, lichen planus, oral squamous cell carcinoma shown to be linked with HPV. The role of HPV in premalignant and malignant oral lesions has been a controversial issue. However, a recent meta-analysis has confirmed HPV as an independent risk factor for oral carcinoma. HPV is the most prevalent infection world wide with several new cases diagnosed every year.2 HPV genome and its implication in oncogenic mechanism Human papilloma virus (HPV) Papilloma viruses are epitheliotropic viruses present in the skin and mucosa of several animals. In humans, more than 70 types have been described.3 Mucosal and genital HPVs, consisting of about 30 types, are divided into low risk (HPVs 6, 11, 42, 43 and 44) and high risk (HPVs 16, 18, 31, 33, 35, 45, 51, 52 and 56), according to their presence in malignant lesions of the cervix.4 Recognized initially as sexually transmitted agents, HPVs are now considered human carcinogens.5 Functionally high risk HPV infection contributes to carcinogenesis and tumor progression predominantly through the actions of two viral oncogenes, E6 and E7. These oncogenes are consistently expressed in cervical cell lines and in human cancers.6,7 Both of these oncogenes interact with and inhibit the activities of critical components of cell cycle regulatory systems, in particular E6 with p53 and E7 with Rb.8,6,7 The E7 protein interacts with pRB and inactivates this cellular protein.9 As a consequence, E2F transcription factor is released from pRB-E2F complex, leading to transcriptional activation of several genes involved in cell proliferation.10 Binding of the E6 protein to the p53 promotes the degradation of the latter through a ubiquitin-dependant proteolysis system. Also of significance is that on completion of the degradation of p53 by the ubiquitin-dependant proteolysis system, the E6 protein is free to interact again with remaining p53 molecules, leading to further degradation of the latter.11 The products of genes E6 and E7 are essential in the process of HPVinduced cellular immortalization and transformation. 12,13The variants are thought to differ in their biologi