Rethinking Human Papillomavirus Vaccine for Oral and Oropharyngeal Cancer Prevention and Global Implementation

Human papillomavirus (HPV) is a DNA virus with over 170 types, which can be divided into high-risk or low-risk types based on their oncogenicity. High-risk types, most notably HPV-16 and -18, have long been associated with cervical cancer. The incidence rate for cervical cancer due to HPV has been steadily declining since the 1980s, and the recently U.S. Food and Drug Administration (FDA)-approved 9-valent HPV vaccine (9vHPV) will likely sustain the downward trend. However, oral and oropharyngeal cancers (OOCs), which are also caused by HPV according to research over the past decade, have seen a rising incidence rate that is projected to increase by 50% over the next 15 years. The mechanism by which HPV causes OOC is similar to that by which it causes cervical cancer. This new finding that HPV not only causes cervical cancer but also OOC changes how clinicians view OOC prevention, diagnosis, and treatment. Unlike HPV-positive genital or anal cancers, OOC are two times more prevalent in men than in women. However, current vaccine programs around the world usually only cover females ages 12 to 26. Moreover, 9vHPV, which targets the L1 major capsid protein of HPV, has not yet been proven to prevent OOC. The high cost of the vaccine along with type-restricted immunity is encouraging scientists to develop a novel vaccine that targets the L2 minor capsid protein; this new vaccine could cover many more HPV types than 9vHPV and potentially prevent OOC in addition to cervical cancer. This article provides an overview of the link between HPV and OOC, the pathogenesis of HPV, an evaluation of the current vaccine as a prophylactic agent, and an exploration of an alternative HPV vaccine. Investigating these topics will allow us to better understand neglected HPV-positive OOCs, re-evaluate the current vaccine strategy that often ignores OOCs, and finally put an end to the HPV epidemic.