Background: Head and neck squamous cell carcinoma (HNSCC) is a significant global health burden. Approximately 25 percent of HNSCC cases are caused by human papillomavirus (HPV). These particular cancers of viral aetiology have been found to have distinct characteristics in regards to presentation, treatment and prognosis. Current advances in vaccinology have the capability to drastically decrease the incidence of HPV-positive HNSCC. Methods: A literature review was undertaken through MEDLINE/PubMED/Ovid databases. The terms “HPV,” “HNSCC,” “carcinogenesis,” “treatment,” “prognosis” and “vaccine” were searched. Only studies published in English were considered with 65 articles selected and analysed. Preference was given to studies published in the last ten years. Results: The incidence of HPV-positive HNSCC is increasing. Infection with HPV can result in cancer through the expression of oncogenic proteins which disrupt normal cellular turnover. Aggressive treatment is often undertaken causing significant morbidity in many patients. A proportion of patients die from this disease, suggesting that these cancers have a considerable impact on society. Conclusion: Human papillomavirus is an infectious agent that is likely transmitted through skin-to-skin contact. The virus integrates into the DNA of the host with the high oncogenic risk genotypes, HPV 16 and 18 being strongly linked to HPV-positive HNSCC development. Prevention through vaccination against these genotypes is currently an option for all individuals. The cervical cancer vaccines immunise non-exposed females against HPV 16 and 18. Vaccination of both males and females will prevent HPV-positive HNSCC.