Therapeutic Vaccines for HPV-Associated Malignancies

Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPVrelated health issues. The approval of Gardasil (R) as a prophylactic vaccine for high-risk HPV 16 and 18 and low-risk HPV6 and 11 for people aged 11-26 in 2006, and of Cervarix (R) in 2009, revolutionized the field and has since reduced HPV infection in young populations. Unfortunately, prophylactic vaccination does not induce immunity in those with established HPV infections or HPV-induced neoplasms, and there are currently no therapeutic HPV vaccines approved by the US Food and Drug Administration. This comprehensive review will detail the progress made in the development of therapeutic vaccines against high-risk HPV types, and potential combinations with other immunotherapeutic agents for more efficient and rational designs of combination treatments for HPV-associated malignancies.