Abstract
Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins p16INK4A and p14ARF and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of p16INK4A is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival.
Highlights
Head and neck cancer is one of the most prevalent malignancies and causes a significant burden of morbidity and mortality each year, accounting for over half a million new cases worldwide, mostly men [1]
It has become clear that in many tumor types specific epigenetic features can be distinguished and that DNA hypermethylation is a major determinant of the “epigenome.” The key question remains whether extended knowledge of cancer epigenetics will result in a new molecular classification of this disease in welldefined and more uniform subcategories
In this review we have focussed on oral and oropharyngeal squamous cell carcinoma as subcategories of head and neck squamous cell carcinoma (HNSCC), which are likely to have their own distinct epigenetic profile. How these differences do occur is not clear, but they might be explained by the alternative aetiologies of head and neck tumors since risk factor exposure is different for age, ethnicity, and geographic location
Summary
Head and neck cancer is one of the most prevalent malignancies and causes a significant burden of morbidity and mortality each year, accounting for over half a million new cases worldwide, mostly men [1] This cancer encloses a wide variety of malignant tumors with squamous cell carcinoma (SCC) being, by far, the most common subtype. Tobacco and alcohol consumption are major aetiological risk factors in head and neck squamous cell carcinoma (HNSCC) [4, 5] These two factors contribute to the development of HNSCC, especially affecting men in advanced age and women due to increasing smoking rates among female gender during the past decades.
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