BACKGROUND AND PURPOSE:

• An association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency has been suggested but has not been confirmed in observational studies
• Concerns about fertility are an impediment to vaccination uptake
• Hviid et al. (JAMA Network Open, 2021) evaluated the risk of primary ovarian insufficiency after quadrivalent human papillomavirus (4HPV) vaccination

METHODS:

• Retrospective cohort study
• Participants
  • Danish-born girls and women
  • 11 to 34 years
  • Follow up from 2007 through 2016
• Exposures
  • 4HPV vaccination
  • No vaccination
• Study design
  • Cox proportional hazards regression was used to estimate hazard ratios (HRs) of primary ovarian insufficiency
  • Adjustments for age, calendar period
  • Propensity score was used to assess health care use, as increased interaction with healthcare system could lead to a greater likelihood of receiving a diagnosis
  • Additional analysis included: Follow-up following vaccination | Age at first vaccination | Calendar period at first vaccination (2007 to 2011 and 2012 to 2016)
• Primary outcome
  • Hospital contacts for primary ovarian insufficiency
  • Rates of primary ovarian insufficiency
• Secondary outcome
  • Secondary composite outcome of amenorrhea and oligomenorrhea

RESULTS:

• 996,300 girls and women | 6,781,166 person-years of follow-up
  • 4HPV vaccinated: 50.8%
  • Unvaccinated: 49.2%
• Primary ovarian insufficiency diagnoses
  • After 4HPV vaccination: 54
  • Unvaccinated: 90
• Median (IQR) age of primary ovarian insufficiency diagnosis: 26.94 (12.68) years
• No significant difference in risk for primary ovarian insufficiency with 4HPV vaccination
  • Adjusted HR 0.96 (95% CI, 0.55 to 1.68)
• No association seen for secondary outcomes (composite amenorrhea and oligomenorrhea)
  • Adjusted HR 1.09 (95% CI, 0.97-1.22)

CONCLUSION:

• There was no association between 4HPV vaccination and increased risk for primary ovarian insufficiency or amenorrhea/oligomenorrhea 
• A limitation of this study is that primary ovarian insufficiency is a relatively rare finding in passive databases
• The authors conclude

The HPV vaccines are cancer-preventing vaccines, and, thus, the lackluster uptake in many countries is disheartening

Our study provides much-needed support for the ovarian safety of the 4HPV vaccine, which is of key importance for clinical and public health personnel when addressing parental concerns about fertility issues associated with vaccination

There is currently little evidence for an association between 4HPV vaccination and primary ovarian insufficiency

On the contrary, the vaccine protects against infections that may decrease fertility 

Learn More – Primary Sources:

Association Between Human Papillomavirus Vaccination and Primary Ovarian Insufficiency in a Nationwide Cohort

Related ObG Topics:

HPV Vaccines: Cochrane Reviews Looks at the Evidence with Multi-Year Follow-Up

The HPV Vaccine Leads to a Reduction in Cervical Precancers in Young Women in the U.S.

MMWR Update: The Impact of Vaccination on HPV Prevalence Among Young Women in the US

Beyond High-Risk Lesions: HPV Vaccination and Impact on Invasive Cervical Cancer Risk