What is the efficacy difference between dose 1 and dose 2 of the Human Papillomavirus (HPV) vaccine?

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Last updated: February 28, 2025View editorial policy

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From the Guidelines

The efficacy of the HPV vaccine is significantly higher after the second dose, with over 90% efficacy against targeted HPV types, compared to approximately 50-80% efficacy after the first dose alone. The HPV vaccine has been shown to provide primary protection against cancers related to HPV types 16 and 18, which are responsible for ∼70% of HPV-related cancers in the United States 1. The 9-valent HPV vaccine (9vHPV) includes coverage for the original 4 HPV types (6,11,16, and 18) in the quadrivalent vaccine and for the high-risk HPV types 31,33,45,52, and 58, which are responsible for an additional 14% of HPV-related cancers in women and 4% of HPV-related cancers in males in the United States 1.

The immune response with a 12-month interval between the 2 doses was more robust than that measured when the interval was only 6 months 1. Geometric mean antibody titers against all HPV types in the 9vHPV vaccine were higher in the 9- through 14-year-old age groups than in the 16- through 26-year-old women 1. For adolescents aged 9-14, a two-dose schedule (0,6-12 months) is now considered sufficient for full protection, while those 15 and older still require three doses (0,1-2,6 months) to achieve optimal immunity 1.

Key points to consider:

  • The HPV vaccine provides significant protection against HPV-related diseases, including cervical cancer
  • The second dose of the HPV vaccine acts as a booster, strengthening and prolonging the immune response initiated by the first dose
  • Completing the recommended dosing schedule is crucial to maximize protection against HPV-related diseases
  • The 9vHPV vaccine provides broader protection against HPV types compared to the quadrivalent vaccine
  • Health care provider recommendation and physician attitude play a major role in the decision to vaccinate against HPV 1

From the Research

Efficacy Difference Between Dose 1 and Dose 2 of the HPV Vaccine

  • The efficacy of the Human Papillomavirus (HPV) vaccine has been studied in various doses, including one-dose, two-dose, and three-dose schedules 2, 3, 4, 5, 6.
  • Studies have shown that two doses of the HPV vaccine can provide comparable immunogenicity to three doses when administered to younger girls 2.
  • A systematic review and meta-analysis found that a two-dose schedule for HPV vaccine provides satisfactory immunological outcomes in adolescent girls, with geometric mean concentrations (GMC) of antibodies against HPV16 and HPV18 being non-inferior or inconclusive compared to a three-dose schedule 6.
  • Another study found that most studies evaluated impact of buffer periods (lag time) for case counting and different intervals between doses for two-dose vaccine recipients, and that significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose 5.
  • The World Health Organization (WHO) has recommended a 2-dose schedule for teens who begin the series before age 15, with doses spaced a minimum of 6 months apart 3, 4.
  • Some jurisdictions with limited resources may consider initiating a one-dose vaccination with the possibility of giving the second dose later in life if judged necessary, to facilitate vaccination implementation and accelerate the impact on cervical cancer and other HPV-associated diseases 2.

Key Findings

  • Two doses of the HPV vaccine can provide comparable immunogenicity to three doses in younger girls 2.
  • A two-dose schedule provides satisfactory immunological outcomes in adolescent girls 6.
  • Significant effectiveness was found among studies that evaluated one, two, and three doses of the HPV vaccine 5.
  • The WHO recommends a 2-dose schedule for teens who begin the series before age 15 3, 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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