Meet the Insidious Players: Review of Viral Infections in Head and Neck Cancer Etiology with an Update on Clinical Trials

Head and neck cancers (HNC) occur in the upper aerodigestive tract and are among the most common cancers. The etiology of HNC is complex, involving many factors, including excessive tobacco and alcohol consumption; over the last two decades, oncogenic viruses have also been recognized as an important cause of HNC. Major etiological agents of nasopharynx carcinoma and oropharyngeal carcinoma include Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), both of which are able to interfere with cell cycle control. Additionally, the association of hepatitis C and hepatitis B infection was observed in oral cavity, oropharyngeal, laryngeal, and nasopharyngeal cancers. Overall prognoses depend on anatomic site, stage, and viral status. Current treatment options, including radiotherapy, chemotherapy, targeted therapies and immunotherapies, are distributed in order to improve overall patient prognosis and survival rates. However, the interplay between viral genome sequences and the health, disease, geography, and ethnicity of the host are crucial for understanding the role of viruses and for development of potential personalized treatment and prevention strategies. This review provides the most comprehensive analysis to date of a vast field, including HNC risk factors, as well as viral mechanisms of infection and their role in HNC development. Additionally, currently available treatment options investigated through clinical practice are emphasized in the paper.