HPV plays a vital role in the development of cervical cancers and oropharyngeal cancers, but it is controversial whether HPV is involved in oral cancer development and to what extent. In this review, the clinical characteristics, diagnosis, treatment, and prognosis of HPV-positive oral cancers are summarized, and the mechanisms of HPV-related oral cancer development are discussed. HPV DNA positivity rates are 20-30% in oral squamous cell carcinoma (OSCC), and HPV16 is the most common high-risk HPV. E6/E7 mRNA positivity rates are 2-6% in OSCC. Detection of both high-risk HPV DNA and E6/E7 mRNA is recommended to determine the presence of active HPV, in agreement with high-risk HPV infection in OSCC. Surgical treatment is the first-line therapy for HPV-positive and -negative oral cancer, but there is no unified view about the prognosis of HPV-positive OSCC patients. HPV16 may play a vital role in malignant transformation in oral epithelial dysplasia, and a model of synergistic carcinogenic impact of HPV and tobacco smoking is predicted. Additionally, it is hypothesized that there are different HPV-associated oral cancers, such as integrated HPV DNA-positive OSCC with stable E6/E7 expression and episomal HPV DNA-positive OSCC. In summary, the role of HPV in oral carcinogenesis seems to be limited because of the low E6/E7 positivity in OSCCs; however, episomal HPV DNA may play a vital role in the malignant transformation of HPV-positive oral premalignant lesions. Further investigation is required to promote new insights into the role of episomal HPV DNA in oral carcinogenesis.
Keywords: Human papillomavirus; Oral cancer; Oral epithelial dysplasia.
© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.