miRNAs in human papilloma virus associated oral and oropharyngeal squamous cell carcinomas

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world with 600,000 new cases diagnosed annually. Tobacco and alcohol use have been associated as the principal etiological factors of this pathogenesis. The incidence of smoking-associated HNSCC has declined, while human papilloma virus (HPV)-associated HNSCC is on the rise. There are currently no clinically validated biomarkers to detect this cancer at an early stage (cancers independent of HPV status). It is well-established that the aberrant expression of miRNAs can lead to tumorigenesis. miRNA expression differences have also been demonstrated in HPV-positive and HPV-negative HNSCC tumor tissues as well as in body fluids. Therefore, miRNAs have the potential to provide an unprecedented insight into the pathogenesis of HNSCC and serve as potential biomarkers. This review addresses HNSCC disease burden and the regulation of miRNA by HPV viral oncoproteins, potential miRNA biomarkers and future perspectives. miRNA provides an unique opportunity to fulfill the current clinical challenge in HNSCC patient management by enabling early detection followed by targeted interventions, leading to a significant reduction in mortality and morbidity.

Keywords::

• head and neck squamous cell carcinoma
• human papilloma virus
• miRNA
• oral and oropharyngeal cancers
• viral oncoprotein E6
• viral oncoprotein E7

Acknowledgement

The authors wish to thank Mr Arutha Kulasinghe for editing the manuscript.

Financial & competing interests disclosure

The authors acknowledge financial support from the Queensland Centre for Head and Neck Cancer, The Queensland Government and the Princess Alexandra Hospital. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, with 600,000 new cases annually.

• Human papilloma virus (HPV)-associated HNSCC is increasing. HPV+ve and HPV–ve HNSCCs display different biological and clinical pathologies, making one debate whether it should be considered as a different tumor group.

• miRNA expression profiles significantly vary between HPV+ve and HPV–ve HNSCC. Therefore, miRNA can be used as potential biomarkers for the detection of and stratification of HNSCC.

• The biological roles of miRNAs in ‘healthy cells’ include cellular proliferation, differentiation, apoptosis, cell cycle regulation and development.

• HPV oncoprotein E6 is documented to dysregulate the expression of miRNAs, 125a, 126, 142-5p, 155, 181a/b, 218, 221, 222, 24a, 29a, 33, 363, 379 and 497.

• HPV viral oncoprotein E7 alters the expression of miRNAs 15a and 224, while in combination, (E6 and E7) it down-regulates the expression of miRNAs 127-3p, 145 and 20b.

• miRNA may hold the promise as biomarkers for detecting HNSCC at an early stage, allowing targeted therapy. This will result in significantly improving the 5-year survival rate.

Notes