Vax  Gardasil

HPV Vaccination Controversy in Japan, Rates Plummet to 1%

Roxanne Nelson, BSN, RN

 

July 20, 2016

http://www.medscape.com

Controversy over human papillomavirus (HPV) vaccination in Japan has led to much confusion among healthcare professionals and parents, with the result that vaccination rates have plummeted, from around 70% to only 1%.

The situation in Japan is summarized by Ryo Konno, MD, of Jichi Medical University, Saitama Medical Center, Japan, speaking in a Lancet Oncology podcast that accompanied an article reviewing breast and cervical cancer screening.

Dr Konno explains that the Japanese government withdrew its recommendation for the HPV vaccine in 2013, after highly publicized cases of alleged adverse events in girls who had been vaccinated. He also says that the side effects are "a psychosomatic reaction" and that the whole controversy was started by an anti-HPV vaccination group.

Dr Konno recalls, "In March 2013, just before the start of a national HPV vaccination program in Japan, there was a major report without any medical evidence that some girls had suffered from severe and chronic pain as a result of the HPV vaccination."

That report, which appeared in the Japanese daily newspaper Asahi Shimbun, gave details of about 50 girls who suffered from complex regional pain syndrome and 100 girls who were absent from school after receiving the HPV vaccine.

According to Dr Konno, this report "was based on information that came from an anti-HPV vaccination group called Vaccine Victims.... These so-called victim girls were put at the forefront of the TV cameras and seen by a large audience."

The story became sensationalized and was repeated on television news programs and then on Internet websites by victim groups, Dr Konno said.

A few months later, in June 2013, the Japanese Ministry of Health, Labor and Welfare (MHLW) withdrew its recommendation for the HPV vaccine because of these reports of serious side effects associated with vaccination, but the vaccines were not withdrawn from the market.

The Minister of Health has said that girls can be vaccinated if parents understand the risks and benefits of the vaccine, but the vaccines could not be actively promoted, Dr Konno explained.

In the meantime, Japan has put in place a scheme to deal with chronic symptoms after HPV vaccination.

A Rocky Road

In Japan, the HPV vaccine Cervarix (GlaxoSmithKline) was approved in 2009; the vaccine Gardasil(Merck & Co) was approved in 2011.

A summary of the HPV vaccination program in Japan was published in May 2014 by the Center for Strategic and International Studies (CSIS). The report was authored by researchers from the Department of Infectious Disease Epidemiology at the London School of Hygiene and Tropical Medicine in the United Kingdom.

"From 2009, Cervarix was partly funded by the Suginami local government. By April 2010, 32 of the 1747 local governments had decided to provide funding for the HPV vaccine. In October 2010, the central and all local governments launched a temporary funding program, and in April 2013, the HPV vaccine was included in the National Immunization Program (but was optional) and was given for free," according to the CSIS report

The report also notes that by June 2013, an estimated 8.29 million people in Japan had received the HPV vaccine.

The report notes that the MHLW announcement of the withdrawal of its recommendation for HPV vaccination was made on June 14, 2013, a day after the World Health Organization (WHO) declared the HPV vaccine to be safe.

The MHLW issued a nationwide notice that although the HPV vaccine could still be given for free to girls aged 12 to 16 years, it should not be proactively promoted. At the time, it said that it was necessary to gather information about the side effects that had been reported.

On the day the announcement was made, a press conference was held by the Vaccine Adverse Reactions Review Committee featuring girls who alleged that they had been affected by the HPV vaccine. The report notes that the girls reported experiencing convulsions, seizures, severe headaches, and partial paralysis.

The report also notes that concerns about the HPV vaccine spread through Japanese social networks. "The absence of any media watchdog in Japan and the relatively lax libel laws mean that newspapers, news programs, social networks and victim support groups are able to publish unverified stories and videos of girls who claim to suffer from adverse events following HPV vaccination," the report authors comment.

Recalling the events, Dr Konno comments in the podcast: "On June 13, the WHO released a safety statement assuring us that the vaccine was safe, but the next day, the Japanese government decided to withdrew its recommendation for the vaccine.... The Ministry of Health did not correct the false claims that had been publicized because they did not have sufficient data to assess the causality of the events."

In December 2014, a symposium held by the Japan Medical Association and the Japanese Association of Medical Sciences concluded that HPV vaccines should be promoted only after issues regarding vaccine safety were settled.

"In general, it is never appropriate to discontinue the immunization program while awaiting the completion of an investigation," Dr Konno asserts.

But that is precisely what happened in Japan, and now it has made an investigation very difficult. "There is serious confusion over medical and legal terms," he noted.

Dr Konno emphasized that in 2013, the Minister of Health did not clearly communicate whether there was a causal relationship between the vaccine and the adverse events but said only that girls could be vaccinated if parents understood the risks and efficacy. Yet the vaccine could not be actively promoted.

"Health officials were so confused," he said. "Consequently, coverage from the vaccine dropped from 70% to only 1%.

He noted that in 2014, a committee associated with the Ministry of Health concluded that there was no evidence to suggest a causal link between chronic pain and the HPV vaccine. "The committee concluded that the girls were suffering from a functional somatic disorder caused by a psychosomatic reaction, so-called conversion disorder," Dr Konno said.

 The girls were suffering from a functional somatic disorder caused by a psychosomatic reaction. Dr Ryo Konno

Yet the Ministry of Health did not provide sufficient communication about this, Dr Konno commented, and media reports have been the only source of information for the public and health professionals for more than 3 years since the recommendation for the vaccine was withdrawn.

Dr Konno notes that a large body of evidence has shown that the benefit of the vaccine outweighs any risk. "But very few newspapers in Japan have reported these international statements, and the TV news has ignored them and reports mostly about the victims.

 This is no longer a medical decision but an emotional-based policy. Dr Ryo Konno

"The Minister of Health still cannot decide to resume the vaccine based on scientific evidence," Dr Konno said. "This is no longer a medical decision but an emotional-based policy."

At the EUROGIN Congress that was held last month in Salzburg, Austria, Dr Konno noted more than 300 of his colleagues from many countries have agreed to sign a petition asking the Japanese government to reinstate the HPV vaccination program.

In addition, a group of Japanese experts in obstetrics and gynecology has recently called for the Ministry to reinstate its recommendation for HPV vaccination, warning that otherwise there may be an increase in "highly preventable cervical and other HPV-related cancers."

Class Action Lawsuit

But the situation in Japan has become more complicated.

On July 27, a class action lawsuit will be filed against the Japanese government, which launched the national vaccination program, and the two manufacturers of the HPV vaccine in four district courts. The lawsuit is being filed on behalf of girls and women who say that they have suffered severe side effects as a result of receiving the vaccine.

When the lawsuit was first announced, there were 12 plaintiffs, aged 10 to 20 years, but according to the Japan Times, that number has since mushroomed to 64. Of this group, 28 will lodge their suit with the Tokyo District Court, six with the Nagoya District Court, 16 with the Osaka District Court, and 14 with the Fukuoka District Court.

They plan to demand 15 million ($140,682) in damages for each plaintiff, for a total of 960 million ($9 million), and may increase the amount in the future, depending on their symptoms.

The lawyers claim that the government's approval of the vaccine was illegal. They claim that the vaccine has caused nerve disorders and other problems due to the excessive immune reactions associated with its use. In addition, they say that the manufacturers bear product liability.

As quoted in the Japan Times, lawyer Masumi Minaguchi stated, "We aim to clarify the responsibilities of the government and the drugmakers through the lawsuits so that the victims can live without anxiety."

 

More Confusion Over Compensation

Independently of the lawsuit, several local governments have compensated girls for health problems believed to be related to HPV vaccination.

But there is confusion over the vaccine compensation program, comment Koichiro Yuji, MD, PhD, from the Institute of Medical Science at the University of Tokyo, Minatoku, and Haruka Nakada, JD, PhD, of the National Cerebral and Cardiovascular Center in Osaka, writing in an article published in Human Vaccines and Immunotherapeutics.

In Japan, approximately 3.38 million girls were vaccinated, and 2584 have complained of health problems, they report. A total of 98 girls who developed health problems applied for assistance from 2011 to 2014.

The majority of these girls (90%) received the HPV vaccine as a nonroutine vaccination, and according to the MHLW, 186 of the girls (0.005%) have not recovered from these events.

As of October 2014, no further cases have been processed. A total of 27 cases were settled, with 18 patients receiving compensation. Nine cases have been declined. The national program for HPV vaccine injury is currently suspended; 71 cases are still pending.

After the national program was suspended, a few of the local governments provided compensation programs for these cases, but the number doing so is extremely low only 16 of 1741 municipalities and 1 of 47 prefectures.

The authors emphasize that the current situation is "confusing due to the discrepancy in HPV vaccine injury compensation between those who received vaccinations under the immunization law and those who received them voluntarily."

HPV vaccine injury compensation programs also differ depending on whether the person was vaccinated before or after April 2013, when the Preventive Vaccination Law was amended.

Those who received routine vaccinations are able to be reimbursed for their medical expenses for both outpatient and inpatient treatment from the MHLW. For those who received nonroutine vaccinations, financial assistance is available from the Pharmaceuticals and Medical Devices Agency on the condition that the health problems warrant the equivalent of hospitalization.

The Ministry of Health is now planning to correct this discrepancy by increasing the level of assistance provided to those with health conditions stemming from nonroutine vaccinations, the authors note. In addition, the ministry plans to consult with an expert panel to draw up its relief program.

"No-fault compensation following adverse events attributed to vaccination is key for vaccine implementation, and the establishment of a new compensation program might be key to calming an anxious public in Japan," write Dr Yuji and Dr Nakada.

They also point out that efforts at compensation seem to be influenced primarily by the activities of HPV vaccine victim support groups and that overall, the suspension of the recommendation for the HPV vaccine has had a negative effect on global health.

"The Japanese government must manage the symptoms that sometimes follow the vaccination, restore public confidence, and provide a strong, evidence-based communication plan for the HPV vaccine," they conclude.

Dr Konno has received honoraria from Roche Diagnostics and BD and is the director of the Executive Board Members of the Japanese Expert Board for the Eradication of Cervical Cancer, which has received unrestricted funding from Qiagen; Merck, Sharp & Dohme; and GlaxoSmithKline. Dr Yuji and Dr Nakada have disclosed no relevant financial relationships. Their article was supported by Grant-in-Aid for Scientific Research.

Lancet Oncol. 2016;16:e305-e312. Abstract

Hum Vaccin Immunother. 2016;12:1321-1324. Abstract