CATEGORY: WOMEN’S HEALTH
One dose of the HPV vaccine protected adolescent girls against the virus types that cause most cervical cancers just as well as two doses did: in a randomized trial of 20,330 girls in Costa Rica, vaccine effectiveness was at least 97% in every study group across five years of follow-up, and the gap between one dose and two amounted to a fraction of one infection per hundred girls.1 For a vaccine the trial’s authors note has been underused around the world, a schedule that is half as long could mean far more girls protected.
The Virus Behind Most Cervical Cancers
HPV—human papillomavirus—is one of the most common viruses passed between people through intimate contact, and two of its types, 16 and 18, are responsible for the large majority of cervical cancers. The HPV vaccine trains the immune system to block the infection before it can take hold, which is why it is given in early adolescence, well before most exposure happens. Multi-dose schedules, though, mean more clinic visits, more cost, and more girls who start the series but never finish it—one reason the researchers set out to learn whether the second dose was adding anything.
Four Groups of Girls, Five Years of Testing
The ESCUDDO trial assigned girls aged 12 to 16 by chance to one of four groups: one or two doses of a two-type (bivalent) vaccine, or one or two doses of a nine-type (nonavalent) vaccine. What counted as failure was a new HPV type 16 or 18 infection that appeared between the first and fifth year and persisted for at least six months on repeat testing—brief infections the immune system clears on its own are common and mostly harmless. Alongside the randomized groups, a separate survey enrolled 3,005 unvaccinated girls and young women, giving the researchers a real-world benchmark for how much infection the vaccine was preventing.
The Margin They Allowed, and the Gap They Found
Going in, whether one dose could match two was genuinely an open question—the researchers wrote that emerging data suggested a single dose may protect, but that the answer was uncertain. A noninferiority trial works like a high-jump bar set in advance: the team declared that one dose would count as equivalent only if it conceded no more than 1.25 infections per 100 participants, and it cleared that bar with room to spare. The observed difference was 0.13 infections per 100 participants in favor of one dose for the bivalent vaccine, and 0.21 per 100 in favor of two doses for the nonavalent vaccine—both far inside the margin. Measured against the unvaccinated group, effectiveness was at least 97% in all four vaccinated groups, and no safety concerns were identified.1
A Kenyan Trial Reached the Same Answer Earlier
The Costa Rica result did not appear out of nowhere. In a randomized trial of 2,275 young women in Kenya, a single dose of either HPV vaccine was tested against a control vaccine: over 18 months, exactly one persistent HPV 16/18 infection occurred in each single-dose vaccine group, against 36 in the control group—an efficacy of 97.5%.2 Worth keeping in view: both trials measured persistent infection, the established precursor the vaccine is designed to block, not cervical cancer itself, which develops over decades—and how long single-dose protection lasts beyond the five years studied is still being tracked.
Key Takeaways
- One dose of either HPV vaccine was statistically noninferior to two doses at preventing persistent HPV 16/18 infection over five years, with effectiveness of at least 97% in every vaccinated group.
- The endpoint was persistent infection—the precursor the vaccine is designed to block—not cervical cancer itself, which takes decades to develop.
- An earlier randomized trial in Kenya found single-dose efficacy of 97.5%, so the result has now appeared independently on two continents.
- How long single-dose protection lasts beyond the five-year study window is still being followed.
References
- 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
- 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