There is a global increase in the prevalence of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) in Australia and New Zealand. Risk factors for HPV-positive OPSCC are male gender, white race, age older than 40 but younger than 59 years old, having multiple lifetime sex partners, having oro-genital and oro-anal sex. High-risk HPV subtypes play a major role in the pathogenesis of OPSCC, however, they play a much lesser role in oral squamous cell carcinoma (OSCC). Among the laboratory tests used to detect oncogenic HPV infection, polymerase chain reaction is a sensitive method but does not reflect the role of HPV in oncogenesis. While widely used, p16 immunohistochemistry is both a sensitive and a specific surrogate marker for oncogenic HPV infection in OPSCC, but not in OSCC. However, it is a useful prognostic marker in OPSCC. The current gold standard to accurately detect oncogenic HPV infection is E6/E7 mRNAin situ hybridization. Because both HPV-positive and p16-positive OPSCC have better short-term prognoses there is current debate and trials on treatment de-escalation in HPV-positive OPSCC. Dental practitioners can play an important role in early diagnosis of HPV-positive OPSCC.