HPV acting on E-cadherin, p53 and p16: literature review

In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains uncertain. A systematic literature search was performed using PubMed, Cochrane library, Science Direct, and the Internet search, with language restricted to English. The search included published studies which dealt with detection methods of HPV-related oral and oropharyngeal cancers and biomolecular studies, particularly regarding the compromising of p53 p16 and e-cadherin’s. P53 Tumour suppressor protein p53 has several functions that are related to maintaining genomic stability and inhibiting cell proliferation in response to DNA damage. For preventing neoplasia to occur, the most important of these functions are cessation of cell growth and induction of either apoptosis or senescence. P16 is a cellular protein involved in cell cycle regulation. It is a cyclin-dependent kinase 4 (CDK4) inhibitor, and is integral to Rb mediated regulation of G1-S phase of the cell cycle. P16 is expressed at a very low level in normal cell as Rb inhibits transcription of p16. Various detection methods ranging from immunohistochemistry (IHC) to molecular techniques have been used to determine the HPV status of HNSCC. E-cadherin, a 120 kDa Type I classical cadherin, is expressed primarily on epithelial cells. It is found on the surface of keratinocytesand Langerhans cells (LC) and E-cadherin mediated adhesion between these cell types is required for LC retention in the epidermis. It is also an important tumour suppressor protein: its loss or inactivation is associated with epithelial-to-mesenchymal transition (EMT), a process involving dedifferentiation, infiltration and metastasis of tumours. Oral carcinogenesis is a multi-factorial process involving socioeconomic, environmental and microbial factors leading to multistep changes. Smoking and tobacco exposure seems to modify the survival and recurrence of HPV positive tumours and should be considered in future trials for risk stratification of HPV positive patients. HPV associated oropharynx cancer represents a distinct clinical and biologic entity with many unresolved issues that will be investigated in future translational, clinical research. We need to further explore and understand why the disease occurs predominantly in males, and whether the natural history of oral HPV infection differences in men and women.