Two-dose bivalent HPV vaccine affords ample protection

Two doses of the bivalent human papillomavirus (HPV) vaccine may effectively prevent incident HPV16/18 infections, with additional cross-protection against HPV31/33/45, over 4 years, as shown in a study from the Netherlands.

“This is one of the first population-based observational studies investigating the two-dose schedule in a regular immunization programme setting and indicates that protection is comparable to three-dose schedules and to observations from randomized clinical trials,” according to the investigators.

The analysis included 2,027 preadolescent girls, of whom 1,098 (54.2 percent) received their shot according to a two-dose schedule. There was a low prevalence of type-specific HPV infections in the first year of follow-up among both vaccinated and unvaccinated girls.

Meanwhile, the prevalence of any HPV type infection rose from 1.7 percent in year 1 to 11.0 percent in year 3 in the unvaccinated group and from 1.1 percent to 8.0 percent in the vaccinated group. HPV51 and HPV74 were the most common high-risk and low-risk type infections, respectively.

During the 4-year follow-up, the highest incidence rate of type specific infection was seen for HPV51 at 5.0 per 1,000 person-years among vaccinated girls and for HPV74 at 9.1 per 1,000 person-years among those who were unvaccinated. [Clin Infect Dis 2021;doi:10.1093/infdis/jiab250]

A multivariable Cox proportional hazards model showed that the two-dose schedule had a pooled vaccine effectiveness of 84.0 percent (95 percent confidence interval [CI], 27.0–96.5) against incident HPV16/18 infections and 86.5 percent (95 percent CI, 39.5–97.08) against cross-protective types HPV31/33/45.

“An important aspect of this study is that the two doses of HPV vaccination were routinely offered in the national immunization programme and replaced the initial three-dose schedule based on immunological data,” the investigators said.

Prior data on the three-dose schedule align well with the observations from the current two-dose study, they added. For example, findings from three-dose vaccine-eligible girls from the catch-up campaign (slightly older at vaccination compared to current participants) indicated that the vaccine effectiveness was 70 percent against incident HPV16/18 infections and 72 percent against HPV16/18/31/45 4 years after vaccination. [RIVM report 2015-0134; J Infect Dis 2018;217:1579-1589]

Another Dutch surveillance study among sexual health clinic visitors who received a three-dose schedule reported a vaccine effectiveness of 89.9 percent against prevalent HPV16/18 infections. [J Infect Dis 2018;217:213-222]

“Our findings are promising regarding future clinical impact of reduced-dosing schedules,” the investigators said.

However, they admitted that they lacked data to estimate vaccine effectiveness against persistent infections—another important endpoint for HPV vaccination according to the World Health Organization. “With prolonged follow-up of the current cohort, these estimates can be reported in the future.” [https://www.iarc.who.int/wp-content/uploads/2018/07/Prophylactic_HPV_VaccineTrials.pdf]