The Role of Human Papillomavirus in Head and Neck Cancers

Abstract

Tobacco and alcohol are well-established risk factors for head and neck squamous cell carcinomas (HNSCC), but it can also develop in individuals not exposed to them. However, only a small proportion of tobacco exposed individuals have developed HNSCC, and there is an emerging tumoral population who lack exposure to these mentioned risk factors, suggesting that others factors can play a role in head and neck carcinogenesis. Over the past two decades, the role of high-risk human papilloma virus (HPV) has been studied through several studies worldwide, and data supporting its role as a causative agent in the development and progression of a subset of HNSCC has been controversial, with considerable variability in frequency depending on the population studied, tumor localization, quality of samples and technical resources utilized for HPV detection. As is the case in cervical and anogenital carcinomas, the most frequently detected high-risk HPVs in HNSCC are the 16 and 18 genotypes. The tonsils and oropharynx are the specific sites associated with higher risk of HPV oncogenic transformation, and investigations suggest that HPV infection in these anatomic sites is an independent risk factor for carcinogenesis. The establishment and maintenance of HPV genomes in the squamous epithelium and HPV-related HNSCC cancer is believed to be originated by oncogenic potential of HPV integration into host DNA genome and their ability to manipulate cell cycle regulators, resulting in deregulated expression of oncoproteins such as E6, which promotes degradation of the tumor suppressor protein p53, allowing cells to evade cell cycle checkpoints, and also E7, which binds to retinoblastoma protein (pRb) and could promote the entrance in S1 phase of cell cycle, leading to disruption of normal cell cycle controls. Following cell division, infected cells leave the basal layer, migrate towards the suprabasal regions and begin to differentiate. Increased understanding of cervical pathogenesis has led to confirmation of HPV as an etiological agent for cancers and consequently to the development of preventive vaccines targeting HPV antigens for the control of cervical cancer. The HPV vaccine was developed as a result of the achievement of core technologies able to produce virus-like