Critical evaluation on roles of macrophagic myofasciitis and aluminum adjuvants in HPV vaccine–induced adverse events

Cervical cancer is caused by human papillomavirus (HPV) infection, which is preventable by HPV vaccines. In Japan, the HPV vaccination rate has remained extremely low due to the concerns for alleged neuropsychological symptoms or “diverse symptoms” following injections of two HPV vaccines, Cervarix and Gardasil, in HPV vaccine lawsuits. In the lawsuits, the attorneys' group has used several manuscripts proposing that aluminum (Al) adjuvant contained in HPV vaccines causes an immune‐mediated disease, called macrophagic myofasciitis (MMF), as well as pathology in the central nervous system (CNS). We scientifically evaluated these manuscripts describing the “Al adjuvant–induced pathologies,” particularly MMF. Although MMF patients have been reported to develop clinical symptoms/signs in various organs, including the CNS, muscle biopsy of the patients and animal experiments demonstrated that MMF pathology was localized only at the injected muscle. No muscle pathology which characterizes MMF was observed in any other muscles; thus, the systemic and neurological signs of MMF cases were irrelevant to localized MMF pathology. We evaluated that MMF‐like pathology was induced as a local inflammatory response following vaccinations; MMF pathology was not the cause of systemic inflammation or “diverse symptoms.” Lastly, MMF cases have been reported after vaccinations with Al‐hydroxide–containing vaccines exclusively. As Al‐hydroxide is a component of Cervarix, but not Gardasil, “diverse symptoms” following two HPV vaccinations in Japan cannot be explained by MMF. Our evaluation would help readers understand the validity of the manuscripts on the role of Al adjuvants or MMF for the alleged “diverse symptoms.”