No therapeutic vaccines have been approved for treatment or cure of HPV and HPV-associated cancers. Currently available HPV vaccines are prophylactic, meaning they can  prevent infection by select types of the virus known to cause disease and abnormal cell development. There exist three FDA-approved HPV vaccines: Gardasil, Cervarix and Gardasil 9. In 2006, the FDA approved the Gardasil vaccine for girls and women aged 9 to 26 and was also approved for use in males aged 9 to 15 in 2014 (Stanley, 248). Gardasil is quadrivalent (4vHPV), meaning it protects against four types of HPV related to cervical cancer and genital warts. Cervarix, the bivalent HPV vaccine (2vHPV), was approved in 2009 for protection against two strains of HPV known to cause cervical cancer in females specifically (Stanley, 248). The nonavalent vaccine (9vHPV), the third and final FDA-approved HPV vaccine, protects against nine types of HPV, including both high-risk (..causing cancer) and low-risk (..causing genital warts) types. This prophylactic vaccine, named Gardasil 9, is the only HPV vaccine available in the United States since it offers the greatest coverage against the virus (Gallego et al., 2020). Gardasil 9 was initially approved in 2014 for use by males and females aged 9 to 26, but its application was expanded in 2018 to include people aged 27 to 45 (“FDA approves,” 2018). 

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Despite their varying coverage, the bivalent, quadrivalent, and nonavalent vaccines share the same biological mechanism. They are classified as subunit vaccines because they use non-living antigenic components of the pathogen, rather than pieces of the living virus, to elicit a humoral immune response in the host (Twitchell, 2018). HPV vaccines are “synthetically manufactured from the oncogenic protein subunit component L1 virus-like particles” (VLPs) (Gallego et al., 2020). L1 is a major structural protein responsible for assembling the icosahedral viral capsid and attaching to host cells. When recombined with a vaccine vector (i.e. yeast or insect virus), L1 is inoculated into a healthy host where it is expressed in large quantities and self-assembles into empty viral capsids classified as VLPs (Stanley, 248). These VLPs “mimic the organization and conformation of authentic native viruses but lack the viral genome,” so they are noninfectious but are still recognized by the immune system as antigenic (Roldão et al., 2017). Consequently, L1 VLPs stimulate the production of neutralizing antibodies that can serve as protection against future HPV infections. It is interesting to note that “antibody titers for 9vHPV are 10 to 100-fold greater than antibody titers produced by natural infection,” conveying the effectiveness of the HPV vaccine (Gallego et al., 2020). 

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All HPV vaccines are administered in a series of two or three doses, depending on the age of initial vaccination. It is recommended that the series is initiated in males and females at 11 or 12 years of age. Those that initiate the vaccine series between ages 9 and 14 should be given two doses in a 6- to 12- month period, while patients who receive their first vaccine between ages 15 and 26 should be given three doses in a 6-month period (Gallego et al., 2020). Ongoing research suggests that a single dose of the HPV vaccine may have the same immunogenic effects as two- and three-dose series (Sankaranarayanan et al., 2018). The duration of protection by a single dose has not been studied beyond seven years, so additional data is needed to determine its long term efficacy in comparison to multiple dose schedules (Sankaranarayanan et al., 2018). Introducing a single-dose HPV vaccine would decrease concerns of accessibility and cost relevant to current vaccine series, ultimately improving HPV vaccination rates.