Japan relaunches its HPV vaccination drive. For thousands of women, it may be too late

Safety concerns led the government to stop recommending the shots in 2013

Three school-age girls in uniform reading books while standing in a library.
Japan’s government again recommends vaccination against human papillomavirus for girls ages 12 to 16.Ferrantraite/
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A version of this story appeared in Science, Vol 376, Issue 6588.Download PDF

Nine years ago, Japan’s health ministry made what many scientists regarded as a terrible mistake. Pressed by antivaccine activists who claimed debilitating side effects, it stopped recommending that Japanese girls get a vaccine that helps prevent cervical cancer. Now, in what public health officials say is a collateral benefit of the success of COVID-19 vaccines, the ministry has finally reversed its position. On 1 April, it will resume recommending that girls ages 12 to 16 get vaccinated against human papillomavirus (HPV)—“an important signal of confidence in the vaccine and its safety,” says Paul Bloem, HPV vaccine strategy lead at the World Health Organization (WHO).

But part of the damage can’t be undone. A modeling study published in The Lancet in 2020 estimated that the negligible vaccination rate between 2013 and 2019 would result in 25,000 preventable cervical cancer cases and up to 5700 deaths over time. A rapid catch-up campaign for the millions of women who missed their shots—which the government has now pledged to undertake—would only prevent 60% of that toll, the study said, because many of the women have already been infected with HPV. The disease causes nearly 3000 deaths annually in Japan, in part because cervical cancer screening rates are low.

Japan initially embraced HPV vaccines, approving GlaxoSmithKline’s bivalent shot—which protects against the two HPV types carrying the greatest cancer risk—in 2009, and Merck & Co.’s quadrivalent vaccine in 2011. In April 2013, the health ministry added both to the national immunization program and started to recommend vaccination.

But just 10 weeks later, an advisory panel suggested suspending the recommendation after a number of girls reported chronic pain, headaches, motor impairment, and other symptoms after immunization. The ministry complied, and the vaccination rate plummeted from about 70% to less than 1% of those eligible.

Such safety problems had not emerged in clinical trials, and in 2017, WHO’s Global Advisory Committee on Vaccine Safety said an extensive review of studies from around the world indicated the vaccines were “extremely safe.” In Japan, a nationwide survey that same year found unvaccinated girls suffer the symptoms attributed to the vaccines at similar rates as vaccine recipients.

Evidence for effectiveness grew as well. The vaccines were approved because they prevent HPV infection, but by the late 2000s, studies showed they reduced the incidence of precancerous lesions as well. Large studies in Sweden and England, reported in 2020 and 2021, respectively, showed vaccination in the early teen years cut the risk of cervical cancer by age 30 by 87% to 88%.

In other countries roiled by reports of side effects—including Denmark, the United Kingdom, and Colombia—authorities kept recommending the vaccines while investigating the claims, says Heidi Larson, head of the Vaccine Confidence Project at the London School of Hygiene & Tropical Medicine. Vaccination rates dipped, but quickly recovered. But in Japan, the government was slow to review the evidence while antivaccine pressure “just became louder and louder,” says Sharon Hanley, a cancer epidemiologist at Hokkaido University. Opponents held press conferences, seminars, and demonstrations, and more than 100 women and girls joined lawsuits against the health ministry and vaccine manufacturers.

Still, calls to reverse the policy increased. In 2017, 17 Japanese academic societies urged the ministry to resume support for vaccination. In 2020 and 2021, a group of parliamentarians led by cervical cancer survivor Junko Mihara asked the health ministry to reconsider its position. The COVID-19 pandemic demonstrated the power of vaccines to reduce severe illness and deaths, which eventually tipped the scales for the HPV vaccines as well, Hanley says. “Antivaccine rhetoric was also not given much space in the media” during the pandemic, she says. (About 80% of Japan’s population is fully vaccinated against COVID-19.) In October 2021, the health ministry’s advisory committee said there was no reason not to restart recommending HPV vaccination.

Many parents are still wary, and local governments and health care providers will have to convince them of the vaccines’ benefits. The shots are in short supply globally, particularly Merck’s latest, also approved in Japan, which protects against nine HPV types. And activists are not giving up. Resuming proactive recommendation “is without any scientific basis and is wrong as public health policy,” says Masumi Minaguchi, a lawyer representing plaintiffs suing the government. The lawsuits are working their way through Japan’s legal system and will continue to generate publicity.

But vaccination supporters believe the spell may have been broken. “I am confident coverage will resume to previous levels as quickly as it fell simply due to peer power,” Hanley says. To her, the 9-year interlude holds an important lesson: “When the government is not supporting [a vaccine], then the people won’t support it.”

Correction, 11 April, 10:30 a.m.: This story has been updated to correct the spelling of Masumi Minaguchi’s name.

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