Abstract
Disruption of DNA methylation patterns is one of the hallmarks of cancer. Similar to other cancer types, human papillomavirus (HPV)-driven head and neck cancer (HNC) also reveals alterations in its methylation profile. The intrinsic ability of HPV oncoproteins E6 and E7 to interfere with DNA methyltransferase activity contributes to these methylation changes. There are many genes that have been reported to be differentially methylated in HPV-driven HNC. Some of these genes are involved in major cellular pathways, indicating that DNA methylation, at least in certain instances, may contribute to the development and progression of HPV-driven HNC. Furthermore, the HPV genome itself becomes a target of the cellular DNA methylation machinery. Some of these methylation changes appearing in the viral long control region (LCR) may contribute to uncontrolled oncoprotein expression, leading to carcinogenesis. Consistent with these observations, demethylation therapy appears to have significant effects on HPV-driven HNC. This review article comprehensively summarizes DNA methylation changes and their diagnostic and therapeutic indications in HPV-driven HNC.
Highlights
This review aims to summarise and evaluate the current state of knowledge on DNA methylation changes associated with human papillomavirus (HPV)-driven head and neck cancer (HNC) and to discuss the diagnostic and therapeutic implications of these methylation changes
Studies conducted to investigate methylation patterns of HPV-driven HNC have demonstrated the ability of HPV oncoproteins to promote DNA methyltransferases (DNMT) activity
Long interspersed nuclear element 1 (LINE1) methylation in HPV-driven HNC compared to healthy controls is not clear, as it has been reported that HPV-negative tumors tend to have hypomethylated LINE1 regions [69]
Summary
Head and neck cancers (HNCs) are a diverse group of cancers arising in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, nasal cavity, and paranasal sinuses [1]. The oropharynx can be considered as the hotspot of HPV-driven cancers in the head and neck region, as the vast majority of these cancers arise in the palatine tonsils and base of the tongue [6,7]. These cancers have clinically and biologically distinct features from their HPV-negative counterparts in terms of their gene expression profiles, mutation burden, epigenetic profiles, and treatment response [8,9,10,11]. This review aims to summarise and evaluate the current state of knowledge on DNA methylation changes associated with HPV-driven HNCs and to discuss the diagnostic and therapeutic implications of these methylation changes
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