Japan Withdraws HPV Vaccine Recommendation for Girls

Nick Mulcahy

June 25, 2013

UPDATED June 25, 2013 — The Japanese government withdrew its recommendation to use human papillomavirus (HPV) vaccines in girls last week, citing concerns from the public about adverse effects, according to news reports.

The announcement is in stark contrast to the pronouncement last week by health officials in the United States that vaccination rates in teenage girls should be increased after a study concluded that estimated vaccine effectiveness is "high."

The Japanese Ministry of Health, Labor, and Welfare is not suspending vaccination, but has instructed local governments not to promote the use of the medicine while analyses are conducted about adverse effects, such as long-term pain and numbness, according to the Japanese newspaper The Asahi Shimbun.

"The decision does not mean that the vaccine itself is problematic from the viewpoint of safety," said Mariko Momoi, who heads a ministry task force looking into the controversy and is a vice president of the International University of Health and Welfare in O-tawara, Tochigi, Japan. "By implementing investigations, we want to offer information that can make the people feel more at ease."

According to a report in the Japan Times, 8.29 million people had received the HPV vaccine as of December 2012, and there were 1968 cases of concerning adverse events reported as of March 2013. Of these adverse events, 106 were described as "serious cases of pains or body convulsions, pains in joints, or difficulty in walking."

Those numbers translate to a rate of 12.8 serious cases of adverse events per 1 million inoculations, according to the report. This compares unfavorably with the 0.9 serious adverse events per million influenza inoculations in Japan and the 2.1 serious adverse events per million inoculations of inactivated polio vaccine. However, the rate seen with the HPV vaccine is lower than that for the Japanese encephalitis vaccine, which is 26.0 serious cases per million inoculations.

According to the Japanese Ministry of Health, Labor, and Welfare Web site, 7 diseases are addressed by regular vaccination: diphtheria, acute poliomyelitis, measles, rubella, Japanese encephalitis, tetanus, and influenza.

The focus of the Japanese inquiry is not on injection-site reactions; instead, it is on systemic reactions.

Merck, which manufacturers and sells one of the vaccines, Gardasil, issued a comment about the Japanese decision.

"While direct causal relationship between the vaccines and serious symptoms observed after inoculation has not been established at this time, we fully understand the anxiety felt by many people in Japan. In response to this decision, we will continue to collaborate with all stakeholders, including (the health ministry), to monitor and verify safety data toward resumption of active promotion for HPV vaccination as soon as possible," according to a company spokesperson quoted in the trade publication Pharmalot.

Both Gardasil, which is a quadrivalent vaccine, and Cervarix (GlaxoSmithKline), which is bivalent, are approved for HPV vaccination in Japan.

GlaxoSmithKline has said that there is "no evidence" that systemic pain is related to Cervarix administration and that the company is providing information to Japanese officials, according to the industry trade Web site BioCentury.

At the same time as the Japanese health authorities were withdrawing their recommendation for HPV vaccination, a top health official in the United States was championing the inoculations.

The endorsement came by way of a study released yesterday by the US Centers for Disease Control and Prevention (CDC), which showed that the vaccine-type HPV prevalence decreased 56% among females 14 to 19 years of age since Gardasil was introduced in 2006.

The results "showing that the types of HPV that commonly cause cervical cancer has dropped by about half in teen girls since 2006 are striking, better than we'd hoped for, and should be a wake-up call for us to increase vaccination rates," CDC director Tom Frieden, MD, MPH, said during a telephone news conference about the study, as reported by Medscape Medical News.

The news was widely covered by major media, including a feature in The New York Times, entitled Will Parents Still Turn Down an 'Anti-Cancer Vaccine?'

In the United States, Gardasil was initially approved for females from 9 to 26 years of age, and approval was expanded to boys and men for preventing genital warts and anal cancer caused by certain types of HPV. GlaxoSmithKline's Cervarix is approved for the prevention of HPV in females 9 to 25 years. However, the new CDC study only involved Gardasil.

According to prescribing information for Gardasil in the United States, the most common systemic reactions in girls in American trials of Gardasil were headache (28.2%) and fever (13.0%). Arthralgia occurred in 1.2% of Gardasil recipients.

In the entire American Gardasil study population of 29,323 individuals, 0.04% had serious systemic adverse reactions that were judged to be vaccine-related by a study investigator.

According to prescribing information for Cervarix in the United States, the most common systemic reactions in girls in American trials were fatigue (54.6%) and headache (53.4%). Arthralgia occurred in 20.7% of Cervarix recipients.

In the entire Cervarix study population of 16,381 females, 5.3% of recipients reported serious adverse reactions.

More From Japan

In Japan, girls will continue to be able to receive the HPV vaccination for free. However, healthcare providers must now inform would-be recipients that the health ministry does not recommend it.

"We welcome the decision not to recommend the vaccination, even though it is a small step," said Mika Matsufuji, head of a parent group that says their children have suffered adverse effects from the vaccination. "Parents can decide whether their children should receive the vaccination or not," she said.


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