What is the recommended dosing schedule for the 9‑valent human papillomavirus vaccine (Gardasil 9) based on age and immune status?

HPV Vaccine Dose Schedule

For individuals starting HPV vaccination before age 15, administer 2 doses at 0 and 6–12 months; for those starting at age 15 or older, or for any immunocompromised person regardless of age, administer 3 doses at 0,1–2, and 6 months. 1

Age-Based Dosing Algorithm

Routine Initiation

• Start HPV vaccination at age 11–12 years (can begin as early as age 9) 2, 1
• Initiating at age 9–10 rather than waiting improves on-time completion rates 3
• Vaccination is most effective when given before sexual debut; approximately 24% of adolescents report sexual activity by 9th grade 1

Two-Dose Schedule (Age <15 at First Dose)

• Eligibility: Any person who receives the first dose before their 15th birthday 2, 1
• Timing: Second dose given 6–12 months after the first dose 2, 1
• Minimum interval: 12 weeks (approximately 3 months) between doses 1
• Key principle: Longer intervals produce stronger immune responses than shorter intervals 1
• Younger adolescents (9–14 years) achieve significantly higher antibody titers than older individuals receiving 3 doses, supporting this reduced schedule 1

Three-Dose Schedule (Age ≥15 at First Dose)

• Eligibility: Any person who receives the first dose at age 15 or older 2, 1
• Timing:
  • Dose 1: Day 0
  • Dose 2: 1–2 months after first dose
  • Dose 3: 6 months after first dose 2, 1
• Minimum intervals:
  • 4 weeks between dose 1 and dose 2
  • 12 weeks between dose 2 and dose 3 1, 3

Special Populations Requiring Three Doses

All immunocompromised persons require a 3-dose schedule regardless of age at initiation. 1, 4 This includes:

• HIV infection 1, 4
• Solid organ transplant recipients 1, 4
• Immunosuppressive therapy 1, 4
• Other immunocompromising conditions 2, 1

Seroconversion rates in transplant recipients are lower (53–68% per HPV type) compared to immunocompetent individuals 1

Catch-Up Vaccination

Ages 13–26 Years

• Universal catch-up vaccination is recommended for all persons through age 26 who are not adequately vaccinated 2, 4, 3
• No shared clinical decision-making required in this age group 4
• Applies regardless of gender, sexual orientation, or prior HPV exposure 3
• Even sexually active individuals should be vaccinated, as they are unlikely to have been infected with all vaccine HPV types 2, 1

Ages 27–45 Years

• Catch-up vaccination is NOT universally recommended 2, 4
• Shared clinical decision-making is advised for selected individuals 2, 4
• The number needed to vaccinate to prevent one cancer rises from 202 (routine program) to 6,500 when extending to age 45 2, 4
• Extending vaccination to age 45 would prevent only an additional 0.5% of cancer cases compared to stopping at age 26 4, 3

Factors favoring vaccination in ages 27–45: 2, 4

• New or anticipated sexual partners
• Men who have sex with men
• Immunocompromised status
• Few lifetime sexual partners

Factors against vaccination in ages 27–45: 2, 4

• Long-term mutually monogamous relationship
• Most sexually active adults already exposed to multiple HPV types
• Substantially lower vaccine effectiveness due to prior infections

HPV vaccines are not licensed for use in adults >45 years. 2, 4

Managing Interrupted Series

Critical principle: If the series is interrupted, do NOT restart—resume from where you left off. 1, 3

• No maximum time interval exists between doses 1
• The vaccine does not lose effectiveness if doses are delayed 1
• The age at first dose determines the schedule, not when subsequent doses are given 1
• Example: A patient who started at age 14 qualifies for the 2-dose schedule even if the second dose is given years later 1

Current Vaccine Product

Gardasil 9 (9-valent HPV vaccine) is the only HPV vaccine available in the United States since January 2017. 1, 4, 3

• Protects against HPV types 6,11,16,18,31,33,45,52,58 1, 4
• Prevents approximately 92% of HPV-related cancers in the United States (~32,100 of 34,800 annual cases) 3
• Prevents ~90% of genital warts caused by HPV types 6 and 11 1, 4
• Administered as 0.5 mL intramuscular injection into the deltoid muscle 1

Important Clinical Considerations

Pre-Vaccination Testing

No pre-vaccination testing is required or recommended 2, 1, 3

• No Pap smear needed 1
• No HPV DNA testing needed 1
• No antibody testing needed 1, 3
• No clinical antibody test can determine immunity status 4, 3

Not Contraindications to Vaccination

The following are NOT contraindications: 1, 4

• History of genital warts
• Abnormal Pap test results
• Positive HPV DNA test
• Prior sexual activity
• Current sexual activity

Contraindications and Precautions

Absolute contraindication: Immediate hypersensitivity to yeast or any vaccine component 1, 4

Precautions: 1, 4

• Defer vaccination in persons with moderate or severe acute illness
• Postpone vaccination during pregnancy; if pregnancy discovered during series, delay subsequent doses until after delivery
• Routine pregnancy testing before vaccination is not required
• Breastfeeding is NOT a contraindication—lactating individuals may safely receive HPV vaccine

Administration Details

• Can be co-administered with other age-appropriate vaccines (e.g., Tdap, MCV4) using separate syringes at different anatomic sites 1
• Patients should sit or lie down for 15 minutes after vaccination due to syncope risk, especially in adolescents 1
• Most common side effect is headache (up to 50% of patients) 1

Cervical Cancer Screening

Cervical cancer screening must continue regardless of HPV vaccination status. 2, 1, 4, 3

• The vaccine does not protect against all oncogenic HPV types 2, 1
• Follow existing cervical cancer screening guidelines for all women 2, 3
• Vaccination does not replace screening 3

Cancer Prevention Impact

HPV vaccination prevents approximately 28,500–32,100 cancers annually in the United States: 4, 3

• Virtually all cervical cancers (100% HPV-associated)
• ~90% of anal cancers
• ~70% of oropharyngeal cancers
• 60–70% of vaginal, vulvar, and penile cancers

Common Pitfalls to Avoid

1. Do not delay vaccination waiting for "optimal" timing—24% of adolescents report sexual activity by 9th grade 1

2. Do not restart an interrupted series—continue from the point of interruption 1, 3

3. Do not require pre-vaccination testing—it provides no actionable information 3

4. Do not withhold vaccination from sexually active individuals—they remain at risk for HPV types not yet acquired 2, 1

5. Do not give only 2 doses to immunocompromised persons—they require 3 doses regardless of age at initiation 1, 4

6. Do not assume vaccination eliminates the need for cervical cancer screening 2, 3