How many doses of Human Papillomavirus (HPV) vaccine, such as Gardasil (quadrivalent human papillomavirus vaccine) or Gardasil 9 (nonavalent human papillomavirus vaccine), are recommended for anal cancer prevention?

From the Guidelines

The recommended HPV vaccination schedule for anal cancer prevention consists of 2-3 doses, depending on age at initiation, with a 2-dose schedule for those under 15 and a 3-dose schedule for those 15 and older or immunocompromised, as recommended by the Advisory Committee on Immunization Practices (ACIP) and supported by recent guidelines 1. The HPV vaccine, including Gardasil and Gardasil 9, has been shown to be effective in preventing anal cancer by targeting HPV types 6,11,16, and 18, with Gardasil 9 offering additional protection against types 31,33,45,52, and 58 1. Key points to consider when administering the HPV vaccine for anal cancer prevention include:

• Age at initiation: individuals under 15 should receive a 2-dose schedule, while those 15 and older or immunocompromised should receive a 3-dose schedule 1
• Vaccine type: both Gardasil and Gardasil 9 are effective, but Gardasil 9 offers broader protection against more HPV types 1
• Timing: vaccination should ideally occur before potential exposure to HPV through sexual contact, but is still beneficial for sexually active individuals who may not have been exposed to all vaccine-preventable HPV types 1 The 9-valent vaccine has been shown to be noninferior to the quadrivalent vaccine and prevents infection and disease related to the additional viral strains included in the vaccine, with a calculated efficacy of 96.7% for the prevention of high-grade cervical, vulvar, or vaginal disease related to those strains 1.

From the Research

Anal Cancer Vaccination Doses

The number of doses for anal cancer vaccination using Human Papillomavirus (HPV) vaccines, such as Gardasil (quadrivalent human papillomavirus vaccine) or Gardasil 9 (nonavalent human papillomavirus vaccine), is as follows:

• For girls aged 9-14 years, a two-dose schedule is recommended 2
• For girls ≥ 15 years of age, a three-dose schedule is recommended 2
• The Centers for Disease Control and Prevention (CDC) also recommends HPV vaccination for everyone through the age of 26 years, and adults aged 27-45 years who might be at risk of new HPV infection and benefit from vaccination 2

Efficacy of HPV Vaccines

The efficacy of HPV vaccines against anal cancer and precancerous lesions has been demonstrated in several studies:

• A study published in 2011 found that the quadrivalent HPV vaccine was effective in preventing anal intraepithelial neoplasia associated with HPV-6,11,16, or 18 infection in men who have sex with men 3
• A study published in 2016 found that the quadrivalent HPV vaccine prevented vaccine-associated persistent anal HPV infections as well as anal intraepithelial neoplasia grades 2-3 (AIN2+) in young MSM not previously infected 4
• A study published in 2020 found that the bivalent vaccine was effective against anal HPV positivity among female sexually transmitted infection clinic visitors in the Netherlands 5
• A study published in 2024 found that HPV vaccination at a younger age was associated with substantially reduced risk of anal HSIL or worse in the general population 6

Vaccine Schedules

The vaccine schedules for HPV vaccination are as follows:

• A two-dose schedule is recommended for girls aged 9-14 years 2
• A three-dose schedule is recommended for girls ≥ 15 years of age 2
• The use of a single-dose HPV vaccination schedule remains controversial 2