Preventing infection with HPV is likely the best strategy to decrease the incidence of anal cancer. The qvHPV and 9vHPV vaccines are highly immunogenic with the same serious adverse event rates as placebo. The qvHPV vaccine has been FDA approved since 2006 for the prevention of cervical, vaginal, and vulvar cancer and anogenital warts in girls and women from 9 to 26 years of age related to HPV types 6, 11, 16, and 18. In 2009, it was FDA approved for prevention of anogenital warts in men and anogenital dysplasia in males and females 9–26 years of age related to the same HPV types. Since being approved for use in women under the age of 26 years, several studies have been conducted evaluating the role of vaccinating other populations. Though not FDA approved for this population, the qvHPV vaccine is immunogenic, safe, and effective in the prevention of anogenital HPV disease in immunocompetent women and men up to 45 years of age. Although efficacy studies are underway in the HIV-positive population, the qvHPV vaccine has been shown to be safe and immunogenic is HIV-positive individuals up to 61 years of age. There is also some evidence that vaccination may decrease recurrence post treatment for HPV-related dysplasia. In 2014, the FDA approved a nine-valent (9vHPV) vaccine for use in 9–26-year-old women followed in 2015 by approval for use in men. In addition to the original four HPV types present in qvHPV, 9vHPV contains antigen an additional five oncogenic HPV types 31, 33, 45, 52, and 58. Current guidelines recommend vaccination in girls and women 9–26 years of age and boys and men 9–21 years of age. It is recommended that men at greater risk be offered the vaccine up to age 26.