Is a single dose of Human Papillomavirus (HPV) vaccine effective?

HPV Vaccination Single Dose Effectiveness

A single dose of HPV vaccine provides high protective efficacy against persistent HPV infections and associated neoplasia with long-term protection demonstrated for up to 15 years post-vaccination. 1

Current Recommendations for HPV Vaccination Dosing

Standard Dosing Recommendations

• For individuals initiating vaccination before their 15th birthday, the recommended immunization schedule is 2 doses of HPV vaccine (0,6–12 month schedule) 2
• For individuals initiating vaccination on or after their 15th birthday, or for persons with certain immunocompromising conditions, the recommended immunization schedule is 3 doses of HPV vaccine (0,1–2,6 month schedule) 2
• HPV vaccination is routinely recommended at age 11 or 12 years, but can be started as early as age 9 years 2

Recent Evidence Supporting Single-Dose Regimens

• A 2024 prospective cohort study with 12-year follow-up demonstrated that a single dose of quadrivalent HPV vaccine provides 92.0% efficacy against persistent HPV 16 and 18 infections, comparable to the efficacy observed with 2-dose (94.8%) and 3-dose (95.3%) regimens 1
• No high-grade precancers associated with HPV 16 and 18 were detected among single-dose vaccinated participants, compared with 8 precancers detected among unvaccinated women 1
• The National Advisory Committee on Immunization (NACI) in Canada recently updated recommendations to support a 1-dose schedule for individuals 9 to 20 years of age based on evidence showing high effectiveness against HPV infection with follow-up of up to 11 years 3

Efficacy Considerations by Dosing Schedule

Single-Dose Efficacy

• Significant effectiveness was found in 18 out of 30 studies that evaluated one-dose HPV vaccination regimens 4
• Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two, and one doses, particularly when vaccination occurred prior to sexual activity 4
• Infectious disease modeling shows that a 1-dose strategy in males and females is expected to have similar health outcomes over the short and long term compared to two doses 3

Multi-Dose Efficacy

• Two-dose HPV vaccine schedules showed no difference in seroconversion from three-dose schedules in many studies 5
• The immune response with a 12-month interval between 2 doses was more robust than that measured when the interval was only 6 months 2
• Geometric mean antibody titers against all HPV types in the 9-valent HPV vaccine were higher in the 9- through 14-year-old age groups than in the 16- through 26-year-old women 2

Important Considerations for Vaccination

Age at Vaccination

• Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination 4
• The rationale for administering the HPV vaccine routinely at the 11- through 12-year-old visit is based on data indicating the greatest protection will be achieved by giving the vaccine before the adolescent becomes sexually active 2
• There is remarkably high incidence of HPV infection after sexual initiation, with cumulative incidence of nearly 40% within the first 2 years after first having sexual intercourse among college women 2

Potential Biases in Effectiveness Studies

• Observational studies of HPV vaccine effectiveness have many biases that could affect interpretation of results 4
• Most biases in studies were rated as serious and would likely result in lower effectiveness estimates with fewer doses 4
• Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias provide more valid effectiveness estimates 4

Special Populations

Immunocompromised Individuals

• Individuals considered immunocompromised and individuals infected with HIV should receive a 3-dose series regardless of age 3
• Vaccination is recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously 2

Adults Over Age 26

• The FDA has licensed HPV vaccines for adults up to age 45, though the ACIP recommends shared clinical decision-making for adults aged 27 through 45 years 2
• Vaccine effectiveness might be low among persons with risk factors for HPV infection or disease (e.g., adults with multiple lifetime sex partners and likely previous infection with vaccine-type HPV) 2

Practical Implementation

• If the HPV vaccine schedule is interrupted, the vaccine series does not need to be restarted 2
• If the series is interrupted after the first dose, the second dose should be administered as soon as possible, and the second and third doses should be separated by an interval of at least 12 weeks 2
• HPV vaccine can be administered at the same visit as other age-appropriate vaccines using separate syringes at different anatomic sites 2

While the traditional multi-dose regimens remain standard in many countries, the emerging evidence supporting single-dose effectiveness represents a potential paradigm shift that could significantly improve vaccination coverage rates and reduce barriers to protection against HPV-related cancers.