Human Papillomavirus Vaccination and Premature Ovarian Failure: A Disproportionality Analysis Using the Vaccine Adverse Event Reporting System

Abstract

Introduction There have been public health concerns about a potential association between human papillomavirus (HPV) vaccines and premature ovarian failure (POF) in young women. Objective To identify a potential safety signal of POF after HPV vaccination using the United States (US) Vaccine Adverse Event Reporting System (VAERS) database. Methods We manually selected relevant MedDRA preferred terms related to POF and identified in VAERS all POF reports in women less than 40 years of age between 2 July 1990 and 14 May 2018, followed by a review of narratives to confirm the cases. We conducted descriptive analyses on age, POF type, HPV vaccine type (HPV2, HPV4, HPV9), time to onset of POF, and dose rank. We described trends in reporting over time and assessed a potential safety signal using the proportional reporting ratio (PRR). Results Of the 228,341 eligible POF reports, 281 (0.1%) were suspected to be associated with HPV vaccines. Median patient age was 15 years (range 11-39 years). POF events consisted mainly of amenorrhea (80.4%) and premature menopause (15.3%). Mean number of reported POF events significantly increased after the first HPV vaccine launch in 2006 with 22.2 POF cases/year up from 1.4 POF cases/year before the launch. PRR was 46.1 (95% confidence interval: 31.7-67.2) and sensitivity analyses yielded similar estimates. Conclusion Our study suggests the presence of a potential safety signal of POF associated with HPV vaccination, which may only be partly attributed to notoriety bias. Due to the well-known limitations of spontaneous reporting data, further investigations are warranted.

MicroRNA-146 attenuates lipopolysaccharide induced ovarian dysfunction by inhibiting the TLR4/NF- κB signaling pathway

“…POI is a disease commonly, which seriously affects women’s reproductive function, even leads to lifelong infertility, affects mental and physical health, and brings great pain to individuals and families. Women under the age of 40 account for 1–2%, and young women under the age of 30 account for 0.1% [ 3 ]. The etiology of POI is unclear, and its pathogenesis is very complex, which has not been clarified so far.…”

Recommendations of the Polish Society of Gynaecologists and Obstetricians, Polish Paediatric Society, Polish Society of Family Medicine, Polish Society of Vaccinology, Polish Society of Oncological Gynaecology, and Polish Society of Colposcopy and Pathophysiology of the Uterine Cervix on prophylactic vaccinations against infections with human papillomaviruses in Poland

“…So far, none of the suspicions has been confirmed in analyses carried out on large vaccinated populations [11][12][13]. However, they remain the subject of further observations and debates [14][15][16].…”

Recommendations of the Polish Society of Gynaecologists and Obstetricians, Polish Paediatric Society, Polish Society of Family Medicine, Polish Society of Vaccinology, Polish Society of Oncological Gynaecology and Polish Society of Colposcopy and Pathophysiology of the Uterine Cervix on prophylactic vaccinations against infections with human papillomaviruses in Poland

“…HPV is the etiological factor of genital warts and recurrent laryngeal papillomatosis. So far, around 200 HPV genotypes have been classified, of which currently 14 (designated as: 16,18,31,33,35,39,45,51,52,56,58,59,66,68) are considered high risk genotypes of neoplastic lesions. The so-called low-risk genotypes 6 and 11 are responsible for the development of most genital warts and recurrent laryngeal papillomatosis.…”

“…So far, none of the suspicions has been confirmed in analyses carried out on large, vaccinated populations [12][13][14]. However, they remain the subject of further observations and debates [15][16][17]. In the HPV4 safety analysis including data from clinical trials and databases, in the 9-year post-marketing period, only syncope and local skin reactions were associated with vaccinations [18].…”