Fewer Doses of the HPV Vaccine Protected Adolescent Girls Just as Well

CATEGORY: WOMEN’S HEALTH

Does the second dose of the HPV vaccine add anything? A trial of 20,330 girls in Costa Rica put that question directly, and the answer was no. One dose protected adolescent girls against the virus types behind most cervical cancers as well as two doses did. Effectiveness ran at 97% or better in every study group across five years of follow-up, and the distance between one dose and two came to a fraction of one infection per hundred girls.¹ The vaccine is underused around the world, the authors note. A schedule half as long could mean far more girls covered.

Two Virus Types, Most of the Cancer

HPV is short for human papillomavirus. It passes between people through intimate contact, and two of its types, 16 and 18, account for the large majority of cervical cancers. The HPV vaccine teaches the immune system to block the infection before it can take hold, which is why it goes to girls in early adolescence, well ahead of most exposure. Longer schedules carry a cost, though. More clinic visits, more money, and more girls who start the series and never come back for the rest of it.

Four Groups of Girls, Five Years of Swabs

None of the girls chose her own schedule. The ESCUDDO trial drew it for her, sorting participants aged 12 to 16 into four arms: one or two doses of a two-type (bivalent) vaccine, or one or two doses of a nine-type (nonavalent) vaccine. Failure had a narrow definition. It meant a new HPV 16 or 18 infection that surfaced between the first year and the fifth and then persisted for at least six months on repeat testing. Short infections the immune system clears by itself are common and mostly harmless, so they did not count. A separate survey of 3,005 unvaccinated girls and young women ran alongside the randomized arms, which gave the researchers a real-world yardstick for how much infection the vaccine was heading off.

A Margin of 1.25, a Gap of 0.13

Going in, the question was genuinely open. The researchers wrote that emerging data hinted a single dose might protect, but that the answer was uncertain. A noninferiority trial works like a high-jump bar set in advance: one dose would count as equivalent only if it gave up no more than 1.25 infections per 100 participants. It cleared that bar with room to spare. The measured difference was 0.13 infections per 100 in favor of one dose for the bivalent vaccine, and 0.21 per 100 in favor of two doses for the nonavalent vaccine. Against the unvaccinated group, effectiveness was at least 97% in all four vaccinated arms, and no safety concerns were identified.¹

Kenya Had Already Found the Same Thing

A randomized trial of 2,275 young women in Kenya tested one dose of either HPV vaccine against a control vaccine. Over 18 months, exactly one persistent HPV 16/18 infection occurred in each single-dose group, against 36 in the control group: an efficacy of 97.5%.² Both trials counted persistent infection, the established precursor the vaccine is built to block. Neither counted cervical cancer itself, which takes decades to develop. How long one dose keeps working past the five years studied is still being tracked.

Key Takeaways

• The endpoint here was persistent infection, the precursor the vaccine is designed to stop, not cervical cancer itself.
• One dose of either HPV vaccine was statistically noninferior to two at preventing persistent HPV 16/18 infection over five years, with effectiveness of at least 97% in every vaccinated group.
• Kenya’s earlier randomized trial put single-dose efficacy at 97.5%, so the answer has now come back the same on two continents.
• Protection beyond the five-year window is still being followed.

References

1. Kreimer AR, Porras C, Liu D, et al. Noninferiority of One HPV Vaccine Dose to Two Doses. The New England Journal of Medicine. 2025;393(24):2421–2433. link
2. Barnabas RV, Brown ER, Onono MA, et al. Efficacy of single-dose HPV vaccination among young African women. NEJM Evidence. 2022;1(5):EVIDoa2100056. link