Is the Human Papillomavirus (HPV) vaccine still effective for a young adult who received doses at 19, 21, and 23 years old?

HPV Vaccine Effectiveness with Delayed Dosing Schedule (Ages 19,21,23)

Yes, the HPV vaccine series completed at ages 19,21, and 23 will still provide protection, but the effectiveness is substantially reduced compared to vaccination at younger ages—likely offering only 22% protection against cervical precancer (CIN2+) rather than the 75% protection seen with vaccination before age 17. 1

Age-Related Effectiveness Decline

The effectiveness of HPV vaccination decreases dramatically with increasing age at vaccination:

• Before age 17: 75% effectiveness against CIN2+ 1
• Ages 17-19: 46% effectiveness against CIN2+ 1
• Age 20 or older: Only 22% effectiveness against CIN2+, which was not statistically significant in screened populations 1

Population-level data from Scotland demonstrates this age gradient starkly: Women vaccinated at ages 19-21 had 5.31 times higher odds of testing positive for HPV 16/18 compared to those vaccinated at ages 15-16 (30.3% vs 7.7% positivity rates). 1

Why Effectiveness Decreases with Age

The reduced effectiveness at older ages occurs because:

• HPV acquisition typically occurs soon after sexual debut, with 39% of college-aged women acquiring HPV within 24 months of first sexual activity 1
• By age 19-26, approximately 50% of individuals have had 4 or more sexual partners, substantially increasing likelihood of prior HPV exposure 1
• The vaccine is prophylactic only—it prevents new infections but does not treat existing infections or clear current HPV-related disease 2, 3
• Prior exposure to vaccine-type HPV eliminates protection for those specific types, and many sexually active adults have already been exposed to HPV 16 and/or 18 1, 4

Current Guideline Recommendations

The American Cancer Society (2016) endorses vaccination through age 26 but with important caveats: 1

• Providers should inform individuals aged 22-26 who have not been previously vaccinated that vaccination at older ages is less effective in lowering cancer risk 1
• The ACS explicitly states that vaccination should not be deferred with the expectation that later vaccination will be similarly effective 1
• The ACS does not endorse shared decision-making for ages 27-45 due to low effectiveness and minimal cancer prevention potential 1, 2

The CDC/ACIP recommends catch-up vaccination through age 26 for all persons not adequately vaccinated, regardless of sexual history or prior HPV exposure 1, 2

Extended Dosing Intervals

Regarding the specific dosing schedule (2-year intervals between doses):

• Standard 3-dose schedule for those ≥15 years is 0,1-2 months, and 6 months 5, 3
• Clinical trials showed that protocol violations, including dosing interval variations up to 1 year, did not negatively impact efficacy 5
• The extended intervals in this case (2 years between doses) exceed studied protocols, but longer intervals between doses generally produce stronger antibody responses 5, 6

Practical Clinical Implications

Despite reduced effectiveness, completing the series still provides meaningful benefit: 1

• Protection against HPV types not yet encountered remains valuable 2, 3
• The nonavalent vaccine (Gardasil 9) protects against 9 HPV types (6,11,16,18,31,33,45,52,58), so even with prior exposure to some types, protection against others is beneficial 2, 3
• No prevaccination testing (Pap or HPV testing) is recommended to determine appropriateness of vaccination 1

Critical Pitfall to Avoid

Do not assume that completing the series at older ages provides equivalent protection to on-time vaccination—the evidence clearly demonstrates age-dependent effectiveness, with the most dramatic decline occurring after age 20. 1, 7 The vaccine remains safe and licensed through age 26, but counseling should acknowledge the substantially reduced cancer prevention potential compared to vaccination at ages 11-12 as recommended. 1