In Japan, a significant number of adolescent girls complained unusual symptoms after human papillomavirus (HPV) vaccination, and the vast majority of them were initially diagnosed as having psychiatric illness because of the absence of pathologic findings, radiological images and specific abnormalities in laboratory test results. Later, these symptoms were supposed to be adverse effects after HPV vaccination, and the recommendation for HPV vaccination was withdrawn by Japanese Ministry of Public Health, Labour and Welfare 4 years and 9 months ago. However, a causal link has not been demonstrated between HPV vaccination and the development of these symptoms. Our study has shown that the period of HPV vaccination considerably overlapped with that of unique postvaccination symptom development, adding that new patients with possible HPV vaccine-related symptoms have not appeared during our recent 28-month follow-up period. This social episode has now subsided in Japan.
This is a preview of subscription content, log in to check access.
This study was supported by a grant from a Health and Labour Science Research Grant on Emerging and Re-emerging Infectious Diseases (Establishment of Treatments and Providing Information on Symptoms after HPV vaccination, H28-001) to S.I. from the Ministry of Public Heath, Labour and Welfare, Japan.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.CrossRefGoogle Scholar
FUTURE II study group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–7.CrossRefGoogle Scholar
Jeurissen S, Makar A. Epidemiological and economic impact of human papillomavirus vaccines. Int J Gynecol Cancer. 2009;19:761–71.CrossRefGoogle Scholar
Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol. 2014;21:135–9.CrossRefGoogle Scholar
Brinth L, Theibel AC, Pors K, Mehlsen J. Suspected side effects to the quadrivalent human papillomavirus vaccine. Dan Med J. 2015;62:A5064.PubMedGoogle Scholar
Brinth LS, Pors K, Theibel AC, Mehlsen J. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papillomavirus. Vaccine. 2015;33:2602–5.CrossRefGoogle Scholar
Palmieri B, Poddighe D, Vadalà M, Laurino C, Carnovale C, Clementi E. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res. 2017;65:106–16.CrossRefGoogle Scholar
Martínez-Lavín M. Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheum. 2014;20:392–3.CrossRefGoogle Scholar
Kinoshita T, Abe R, Hineno A, Tsunekawa K, Nakane S, Ikeda S. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53:2185–200.CrossRefGoogle Scholar
Ozawa K, Hineno A, Kinoshita T, Ishihara S, Ikeda S. Suspected adverse effects after human papillomavirus vaccination: a temporal relationship between vaccine administration and the appearance of symptoms in Japan. Drug Saf. 2017;40:1219–29.CrossRefGoogle Scholar
Carnovale C, Damavandi PT, Gentili M, Pozzi M, Antoniazzi S, Radice S, et al. On the association between human papillomavirus vaccine and sleep disorder: evaluation based on vaccine adverse reporting systems. J Neurol Sci. 2017;373:179–81.CrossRefGoogle Scholar
Hirai T, Kuroiwa Y, Hayashi T, Uchiyama M, Nakamura I, Yokota S, et al. Adverse effects of human papillomavirus virus vaccination on central nervous system: neuro-endocrinological disorders of hypothalamo-pituitary axis. Auton Nerv Syst. 2016;53:49–64.Google Scholar
Kuroiwa Y, Yokota S, Nakamura I, Nakajima T, Nishioka K. Human papilloma virus vaccination (HPVV)-associated neuro-immunopathic syndrome (HANS): a comparative study of the symptomatic complex occurring in Japanese and Danish young females after HPVV. Auton Nerv Syst. 2018;55:21–30.Google Scholar