Abstract
H uman papillomavirus (HPV) is considered the main cause of the increasing incidence rates of oropharyngeal squamous cell carcinoma (OPSCC), and soon, the global burden of HPV-related OPSCC is predicted to exceed that of cervical cancer. Moreover, a different molecular profile for HPV-related OPSCC has been described, opening new promising targeted therapies and immunotherapy approaches. Epigenetic and microbiome-based exploration of biomarkers has gained growing interest with a view to the primary oropharyngeal cancer (OPC) screening. Understanding the role of the epigenetic mechanism and the changes that occur during pathogenesis shows appreciable progress in recent years. The different methylation status of DNA and miRNAs demonstrates the value of possible biomarkers discriminating even in different stages of dysplasia. Through whole-genome bisulfite sequencing, differentially methylated regions (DMRs) hold the key to recover missing information. O n the other hand, the microbiota investigation signifies a new biomarker approach for the evaluation of OPC. Along with known cofactors playing a major role in microbiota differentiation, HPV-related cases must be explored further for better understanding. The dynamic approach of the shotgun metagenomic sequencing will robustly fill the gap especially in species/strain level and consequently to biomarker detection. The constantly growing incidence of HPV-related OPC should lead us in further investigation and understanding of the unique features of the disease, more accurate diagnostic methods, along with the development and implementation of new, targeted therapies. This paper comprehensively reviews the significance of biomarkers based on epigenetics and microbiome profile in the accuracy of the diagnosis of the HPV-related cancer in the oropharynx.
Highlights
EpidemiologyHead and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide (Stein et al, 2015)
Human papillomavirus (HPV) was first discovered by Jabłoñska and Gerard Orth in 1978 where they demonstrated that the virus was able to infect basal keratinocytes in the skin or mucosal membranes (Human Papillomaviruses, 2006)
The assessment of p16 expression is routinely used along with the diagnosis of HPV infection, the gold standard remains the detection of HPV E6 and E7 messenger RNA expression via quantitative reverse transcription-polymerase chain reaction (PCR)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the eighth most common cancer worldwide (Stein et al, 2015). The association between p16 expression and HPV positivity does not exist among the nonOPCs. the assessment of p16 expression is routinely used along with the diagnosis of HPV infection, the gold standard remains the detection of HPV E6 and E7 messenger RNA (mRNA) expression via quantitative reverse transcription-PCR (qRT-PCR). The assessment of p16 expression is routinely used along with the diagnosis of HPV infection, the gold standard remains the detection of HPV E6 and E7 messenger RNA (mRNA) expression via quantitative reverse transcription-PCR (qRT-PCR) This is indicative of a transcriptionally active virus within tumor cells (Ndiaye et al, 2014). Some challenges exist, including the potential difficulty of identifying the primary tumor site in advanced-stage OPSCC and a lack of case-controlled studies, better prediction of HPV-OPSCC prognosis is expected using both the clinical and the pathologic data sets (Wang et al, 2015). Non-invasive screening must be further investigated through large-scale studies for early diagnoses, such as the cervix cases (Agorastos et al, 2019)
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