Single-dose HPV vaccine noninferior to two doses, large trial finds
A trial randomized more than 20,000 adolescent girls in Costa Rica to receive one or two doses of human papillomavirus (HPV) vaccine between November 2017 and February 2020 and followed them for 60 months to assess the rate of new HPV type 16 or 18 infections.
One dose of either a bivalent or nonavalent human papillomavirus (HPV) vaccine protected against HPV16 or HPV18 infection and was noninferior to two doses, a randomized controlled trial found.
To determine whether a single dose of an HPV vaccine would provide similar protection to two doses, researchers randomized 20,330 girls ages 12 to 16 years in Costa Rica to receive one or two doses of a bivalent HPV vaccine or one or two doses of a nonavalent HPV vaccine between November 2017 and February 2020. New HPV type 16 or 18 infection from month 12 to month 60 and persistence for at least six months was the primary endpoint. Investigators defined the noninferiority margin as 1.25 infections per 100 participants. To assess effectiveness, trial participants were compared with 3,005 unvaccinated participants enrolled in a survey. Findings were published by the New England Journal of Medicine on Dec. 3.
The researchers found that one vaccine dose was noninferior to two doses in preventing HPV16 or HPV18 infection for both the bivalent and nonavalent vaccines. The rate difference was −0.13 infection per 100 participants (95% CI, −0.45 to 0.15) between one and two doses of the bivalent vaccine and 0.21 infection per 100 participants (95% CI, −0.09 to 0.51; ) between one and two doses of the nonavalent vaccine (P<0.001 for noninferiority for both comparisons). The effectiveness was 98.2% (95% CI, 96.1% to 99.6%) for one dose of the bivalent vaccine and 97.8% (95% CI, 95.6% to 99.3%) for two doses; efficacy for the nonavalent vaccine was 97.0% (95% CI, 94.3% to 99.1%) for one dose and 98.5% (95% CI, 96.7% to 99.7%) for two doses. No safety concerns were identified.
Limitations include that data were lacking on previous HPV infection rates among survey participants and that trial participants were only followed for five years. “The evidence from this trial supports the WHO [World Health Organization] alternative recommendation for single-dose HPV vaccination to achieve higher coverage while maintaining sufficiently high efficacy,” the study authors concluded.
An accompanying editorial endorsed this finding, calling the results the “strongest evidence to date” to support the WHO recommendation. “We have the evidence and tools to eliminate cervical cancer. What remains is the collective will to implement them equitably, effectively, and now,” the editorialists wrote.