A growing proportion of oropharyngeal cancers are related to HPV infection. More than 130 HPV types are known and classified as lowrisk or high-risk based on their oncogenic potential; HPV16 is the most commonly found and is present in ~90% of HPV-OSCCs. Two metaanalyses of case-control studies have provided epidemiological evidence of the causative role of HPV in OSCC supported strong correlation between HPV16 exposure and HNSCC in certain anatomical sites. Indeed, a strong correlation has been described between HPV-16 detection at the time of diagnosis with tonsillar cancer. Biologically, the integration of high-risk HPV DNA into the host genome can lead to the expression of oncogenes E6 and E7 in the host cell; however, 60% of HPV-positive OSCC can contain extrachromosomal (episomal) virus. The E6 oncogene provokes the degradation of TP53. The E7 oncogene is implicated in binding and destabilizing of the tumor suppressor retinoblastoma (pRb). HPV-OSCC differs from HPV-driven cervical cancer, during which cervical smear and HPV DNA are widely used for screening in clinical practice; in HPV-OSCC there's no identified oropharyngeal premalignant lesion and the presence of HPV DNA in the oral cavity or oropharynx is not directly linked to subsequent development of HNSCC. Although detection of HPV16 DNA by Polymerase Chain Reaction (PCR) in both salivary oral rinses and plasma has demonstrated marked sensitivity and specificity, it has not been incorporated into clinical practice as a screening tool