Human Papillomavirus Genotype and DNA Methylation of TP53, PIK3CA as Integrated Biomarkers for Oropharyngeal Carcinogenesis -A Review

Abstract

Head and neck squamous cell carcinoma (HNSCC), especially oropharyngeal squamous cell carcinoma (OPSCC), has recently been found to be significantly associated with human papillomavirus (HPV) infection. The aim of this review is to understand the genetic roles of HPV, methylation of TP53, and PIK3CA in the development of OPSCC. Research publication articles from PubMed and many other were searched using goggle search engine. Over fifty journals of international reputes were obtained, out of which more than forty-five gives reputable results information on HPV and methylation of TP53, PIK3CA integration in OPSCC. PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC in patients treated with definitive chemo radiation (CRT). Recent landmark sequencing studies have demonstrated gene expression profiles and somatic mutations such as TP53, CDKN2A, PTEN, PIK3CA, EGFR, HRAS, FBXW7 and NOTCH in diverse anatomical sites of HNSCC. Head and neck squamous cell carcinoma (HNSCC) encompass a heterogeneous group of malignant neoplasms arising from the non- keratinizing epithelium of the upper aero digestive tract. Therefore, HPV, methylation of TP53 and PIK3CA are found to be indispensable Biomarkers in the development of OPSCC. Recent comprehensive large-cohort DNA  methylation analyses at a genome-wide scale have revealed that there is an HPV-associated HNSCC subtype with increased DNA methylation. However, there is still room for elucidation of the mechanism of HPV and DNA methylation. A more detailed understanding of the molecular basis of this subtype might lead to the development of new therapeutic strategies, such as therapeutic de-escalation in this subtype.