What is the effectiveness of Gardasil 9 (Human Papillomavirus 9-valent Vaccine) at preventing Human Papillomavirus (HPV) infection?

Effectiveness of Gardasil 9 in Preventing HPV Infection

Gardasil 9 is highly effective at preventing HPV infection, with up to 97% effectiveness against cervical, vulvar, and vaginal cancer precursor lesions related to the 9 HPV types it targets, and provides protection against approximately 90% of HPV-related cancers when administered before HPV exposure. 1, 2

Coverage and Protection

Gardasil 9 (9-valent HPV vaccine) provides protection against:

• The original 4 HPV types in the quadrivalent vaccine (6,11,16,18)
• Five additional high-risk HPV types (31,33,45,52, and 58)
• Together, these 9 types are responsible for:
  • Approximately 90% of cervical cancers
  • 90% of genital warts (types 6 and 11)
  • Significant protection against vulvar, vaginal, anal, penile, and potentially oropharyngeal cancers 1, 3

The expanded coverage of Gardasil 9 represents a substantial improvement over earlier vaccines:

• HPV types 16 and 18 alone are responsible for ~70% of HPV-related cancers
• The additional 5 types in Gardasil 9 account for another 14% of HPV-related cancers in women and 4% in men 1

Efficacy Data

In Clinical Trials

• In women who were HPV-naive before vaccination:
  • 100% efficacy (97.96% CI, 76% to 100%) for preventing HPV16/18-related CIN2/3 and adenocarcinoma in situ 1
  • 100% efficacy (97.5% CI, 88% to 100%) for preventing HPV6/11/16/18-related external genital warts or vulvar/vaginal intraepithelial neoplasia 1
  • 97% effectiveness against cervical, vulvar, and vaginal cancer precursor lesions related to the 5 additional types in Gardasil 9 1

In Real-World Settings

• Post-vaccination studies have demonstrated:
  • 64% decrease in 4vHPV type prevalence among girls 14-19 years of age
  • 34% decrease among women 20-24 years of age 1
  • Notable decreases in HPV 6/11/16/18 among vaccinated compared to unvaccinated women 4

Factors Affecting Effectiveness

Age at Vaccination

• Optimal timing: Vaccination is most effective when administered before exposure to HPV (before sexual activity begins)
• Higher immune responses are observed in younger age groups:
  • Geometric mean antibody titers against all HPV types were higher in 9-14 year-olds compared to 16-26 year-olds 1
  • This supports the recommendation for routine vaccination at ages 11-12 years 1, 2

Prior HPV Exposure

• Critical limitation: The vaccine is not effective against current HPV infections with vaccine types 5
• In intention-to-treat analyses including women regardless of baseline HPV status:
  • Reduction of HPV16/18-related CIN2/3 or AIS was only 39% (95% CI, 23% to 52%)
  • Reduction of HPV6/11/16/18-related genital warts was 69% (95% CI, 58% to 77%) 1
• Individuals with prior exposure to some HPV types can still benefit from protection against other types included in the vaccine 2

Dosing Schedule

• Current recommendations:
  • Ages 9-14 years: 2-dose schedule (0,6-12 months)
  • Ages 15-26 years: 3-dose schedule (0,1-2,6 months)
  • Immunocompromised individuals: 3-dose schedule regardless of age 1, 2
• The immune response with a 12-month interval between doses was more robust than with a 6-month interval 1

Special Considerations

Duration of Protection

• Follow-up data from clinical trials have shown protection for up to 4-5 years 1
• Longer-term studies are ongoing to evaluate antibody persistence 1
• The need for booster doses has not yet been established 6

Herd Protection

• HPV vaccination has demonstrated herd protection effects, benefiting unvaccinated individuals through reduced circulation of vaccine-type HPV in the population 4

Limitations and Caveats

1. Pre-existing infections: Gardasil 9 is prophylactic, not therapeutic - it cannot treat existing HPV infections 2

2. Incomplete coverage: While covering 9 HPV types, it does not protect against all oncogenic HPV types

3. Need for continued screening: Regular cervical cancer screening is still recommended regardless of vaccination status 2

4. Population differences: Effectiveness may vary based on sexual behavior and prior HPV exposure - efficacy is highest in individuals with no prior HPV exposure 1, 2

5. Long-term efficacy: While short to medium-term efficacy is well-established, longer-term protection beyond 5 years continues to be studied 1, 6

In conclusion, Gardasil 9 represents a significant advancement in HPV prevention with its expanded coverage of HPV types and high efficacy when administered before HPV exposure. For optimal protection, vaccination should occur before the onset of sexual activity.