Authors: Hirokuni Beppu, Masumi Minaguchi, Kiyoshi Uchide, Kunihiko Kumamoto, Masato Sekiguchi, Yukari Yaju
The human papillomavirus (HPV) vaccine has been linked to a number of serious adverse reactions. The range of symptoms is diverse and they develop in a multi-layered manner over an extended period of time. The argument for the safety and effectiveness of the HPV vaccine overlooks the following flaws: (i) no consideration is given to the genetic basis of autoimmune diseases, and arguments that do not take this into account cannot assure the safety of the vaccine; (ii) the immune evasion mechanisms of HPV, which require the HPV vaccine to maintain an extraordinarily high antibody level for a long period of time for it to be effective, are disregarded; and (iii) the limitations of effectiveness of the vaccine. We also discuss various issues that came up in the course of developing, promoting and distributing the vaccine, as well as the pitfalls encountered in monitoring adverse events and epidemiological verification.
In this paper, we review the adverse reactions following human papillomavirus (HPV) vaccination in Japan, and the measures taken by the Ministry of Health, Labour and Welfare (MHLW) (1) to withdraw active recommendation of the vaccine. These measures triggered domestic and international controversy. We also discuss various problems that occurred while developing, promoting and distributing the vaccine; the pitfalls encountered in monitoring adverse events and epidemiological verification; and the influence of big pharma on healthcare policy and research.
- Overview of the HPV vaccine issue in Japan
HPV vaccines were approved later in Japan than in the western countries (October 2009 for Cervarix, and July 2011 for Gardasil). The vaccination rate was initially low. However, after a campaign for the promotion of the vaccine, which led to government subsidisation of the cost of the vaccine in November 2010, the vaccination rate increased exponentially. This was followed by an unexpected increase in reports of adverse events (AEs). Importantly, these vaccines gave rise to a large number of serious AEs. Table 1 shows the number of reports of serious AEs/adverse drug reactions (ADRs), defined according to the ICH E2A guidelines (2), submitted with respect to HPV vaccines by vaccine manufacturers and medical professionals at the end of February 2016 (3). These numbers far exceed those for other vaccines, even if one allows for the probability that vigilance would be higher for a newly introduced vaccine than an older, time-tested one (4, 5) (Fig. 1). As these data have been compiled from voluntary reports, the actual incidence of AEs may well be far higher (6, 7).