Epigenetics of oropharyngeal squamous cell carcinoma: opportunities for novel chemotherapeutic targets

Abstract

Epigenetic modifications are heritable changes in gene expression that do not directly alter DNA sequence. These modifications include DNA methylation, histone post-translational modifications, small and non-coding RNAs. Alterations in epigenetic profiles cause deregulation of fundamental gene expression pathways associated with carcinogenesis. The role of epigenetics in oropharyngeal squamous cell carcinoma (OPSCC) has recently been recognized, with implications for novel biomarkers, molecular diagnostics and chemotherapeutics. In this review, important epigenetic pathways in human papillomavirus (HPV) positive and negative OPSCC are summarized, as well as the potential clinical utility of this knowledge.This material has never been published and is not currently under evaluation in any other peer-reviewed publication.

Keywords: Chemotherapy; Epigenetics; Human papillomavirus; Oropharyngeal cancer; Squamous cell carcinoma.

Fig. 1

Summary of epigenetic pathways involved in oropharygeal squamous cell carcinoma. Oncogenic human papillomavirus integrated into the human genome, resulting in the expression of HPV-associated proteins E6 and E7. This results in alterations of p53, Rb and Polycomb Repressive Complex (shown here including EZH2, SUZ12, EED and HOXD) related pathways with downstream epigenetic deregulation in OPSCC. Overexpression of P16INK4a occurs as a result of loss of Rb and is used as clinical surrogate marker for HPV-positive OPSCC. *FOXM1 and HOTAIR are presumed to have a role in OPSCC based on studies in OCSCC