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Two-dose HPV vaccine schedule as good as three-dose

Study supports US decision to set two-dose schedule for all three licensed HPV vaccines

Louise Prime

Tuesday, 22 November 2016

Adolescents’ antibody response to two doses of a 9-valent human papillomavirus (HPV) vaccine is as good as their response to a three-dose schedule, according to the latest research.* Experts pointed out** that evidence from this study, published online today in JAMA, supports the US’ decision last month to recommended a two-dose schedule for all three licensed HPV vaccines in the under-15s.

Researchers led from the University of Bergen in Norway collaborated on an international study to see whether or not HPV type-specific antibody responses would be non-inferior among 9-14-year-old girls and boys who had received two doses of the 9-valent HPV vaccine, compared with responses among 16-26 year-old girls and young women who had had the standard three doses of the same vaccine.

They enrolled a total of 1,518 participants (753 girls and 451 boys) from 52 sites across 15 countries. These were made up of five groups: 301 girls aged 9-14 years, to receive two doses six months apart; 301 boys aged 9-14 years, to receive two doses six months apart; 301 girls and boys aged 9-14 years, to receive two doses 12 months apart; 301 girls aged 9-14 years, to receive three doses over six months; and a control group of 314 adolescent girls and young women aged 16-26 years, to receive three doses over six months.

The study authors analysed data from 1,377 of the 1,474 people who completed the study. They found that at four weeks after the last dose of HPV vaccine, HPV antibody responses in girls and boys given two doses were non-inferior to HPV antibody responses in adolescent girls and young women given three doses. However, they pointed out that further research is needed to assess the persistence of antibody responses, as well as the effect on clinical outcomes.

They pointed out that an effective two-dose regimen could improve adherence to HPV vaccination programmes as it entails fewer visits, especially as vaccination rates remain suboptimal in many countries. They added: “Co-administration of the 9-valent HPV vaccine with diphtheria, tetanus, pertussis, polio, and meningococcal vaccines could also be completed at the same visit … use of a two-dose vaccination schedule could potentially reduce the total costs of HPV vaccination.”

In their accompanying editorial, experts from the US Centers for Disease Control and Prevention (CDC) and elsewhere pointed out that the CDC’s “important policy decision” in October 2016 to recommend a two-dose schedule for adolescents starting the HPV vaccination series before the age of 15 years is supported by the results of this new study as well as previously published data.

They said: “During the first decade of the HPV vaccination programme, knowledge has increased about these highly effective HPV vaccines. Population-level effects of vaccination programmes on infection and disease outcomes have exceeded expectations in many countries, and extensive safety evaluations have not identified concerns.

“In the second decade, reduced dose schedules might help achieve higher HPV vaccination coverage, advance HPV vaccine programme introductions in more countries, and further reduce the burden of HPV-associated cancers and disease worldwide.”


* Iversen O-E, Miranda MJ, Ulied A, et al. Immunogenicity of the 9-valent HPV vaccine using 2-dose regimens in girls and boys vs a 3-dose regimen in women. JAMA. Published online 21 November 2016. doi:10.1001/jama.2016.17615. [NB The study was sponsored and funded by Merck & Co, which manufactures the quadrivalent and nonavalent HPV vaccines.]

** Markowitz LE, Meites E, Unger ER. Two vs three doses of human papillomavirus vaccine: new policy for the second decade of the vaccination program. JAMA. Published online 21 November 2016. doi:10.1001/jama.2016.16393.

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