CLINICAL QUESTION
Is one dose of human papillomavirus (HPV) vaccine as effective as two doses?
BOTTOM LINE
The large, well-designed study convincingly demonstrates that one dose of HPV vaccine is noninferior to two doses. (Level of Evidence = 1b)
SYNOPSIS
HPV vaccination is highly effective at preventing infection and cervical cancer, but it is underused. Barriers to vaccination are cost and the inability to return for follow-up to receive a second vaccination. The study enrolled unvaccinated females aged 12 to 16 years in Costa Rica from 2017 to 2020, when vaccination in that age group was not routine. Patients with previous infection were excluded. At enrollment, 20,330 participants were randomized to receive a bivalent (subtype 16 and 18 only) or nonavalent vaccine; 6 months later, they were randomized to receive a second dose of the same vaccine or vaccination with a diphtheria, pertussis, and tetanus vaccine as a control to maintain masking. Another group of unvaccinated females aged 16 to 21 years had HPV testing at baseline and at 6 months to allow for determination of vaccine efficacy.
For noninferiority assessment of one dose vs two doses of each vaccine, a noninferiority margin of no more than 1.25 additional infections per 100 women was prespecified. Vaccinated participants were followed up for 5 years with a clinic visit and testing for HPV at each visit from age 15 years onward. Visits occurred annually until age 15 years and then every 6 months. The primary outcome was an HPV infection that lasted at least 6 months and was assessed in the per-protocol population that received two doses (approximately 85% of participants in each group).
Overall vaccine effectiveness compared with the unvaccinated cohort was between 97.0% and 98.5% for all four groups. For the outcome of infection with subtypes 16 or 18, one dose was noninferior to two doses for the bivalent and nonavalent vaccines, with risk differences of −0.13 infections for the bivalent vaccine and +0.22 infections for the nonavalent vaccine per 100 people. For prevention of the nine subtypes in the nonavalent vaccine, one dose was noninferior to two doses (risk difference was +0.56 infections per 100 persons).
Study Design: Randomized controlled trial (double-blinded)
Funding Source: Government and foundation
Allocation: Concealed
Setting: Population-based
