What are the common side effects of Human Papillomavirus (HPV) vaccination?

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Last updated: June 12, 2025View editorial policy

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From the Guidelines

The most common side effects of HPV vaccination are generally mild and temporary, including pain, redness, or swelling at the injection site, fever, headache, fatigue, muscle or joint pain, and nausea, as reported in a study published in 2019 1. These side effects typically resolve within a few days. Some people may experience fainting, particularly in adolescents, which is why patients are typically advised to remain seated or lying down for 15 minutes after receiving the vaccine. Serious allergic reactions are extremely rare but can include difficulty breathing, hives, or swelling of the face and throat. The HPV vaccines (Gardasil 9 is currently the only one available in the United States) have been extensively studied and have a strong safety profile, as noted in a study from 2018 1. These side effects are generally considered minor compared to the benefits of protection against HPV-related cancers and diseases. The vaccine is typically administered in a 2-dose schedule for those who start the series before age 15, with doses given 6-12 months apart, or a 3-dose schedule for those who start at age 15 or older, with doses given at 0,1-2, and 6 months, as recommended by the Advisory Committee on Immunization Practices in 2019 1. Key points to consider include:

  • The HPV vaccine has a strong safety profile, with serious adverse events occurring in less than 0.1% of persons, as reported in a study from 2007 1.
  • The vaccine is highly effective in preventing HPV-related cancers and diseases, with a 97% effectiveness in protecting against cervical, vulvar, and vaginal cancer precursor lesions related to the 5 additional types, as noted in a study from 2017 1.
  • The vaccine is recommended for individuals 11 through 12 years of age, with a 2-dose schedule for those who start the series before age 15, and a 3-dose schedule for those who start at age 15 or older, as recommended by the Advisory Committee on Immunization Practices in 2019 1.

From the Research

Common Side Effects of HPV Vaccination

  • Injection site reactions, such as pain, swelling, and redness, are common side effects of HPV vaccination, usually of short duration and resolving spontaneously 2, 3
  • Systemic reactions, including fatigue, fever, gastrointestinal symptoms, and headache, have been reported, but are generally mild and self-limited 2, 3
  • Post-vaccination syncope has occurred, but can be avoided with appropriate care 2
  • Serious vaccine-attributable adverse events, such as anaphylaxis, are rare 2

Less Common Side Effects

  • Erythema multiforme, a cutaneous syndrome characterized by symmetric target lesions, has been reported as a rare side effect of the quadrivalent HPV vaccine 4
  • Abnormal pregnancy outcomes following inadvertent administration of HPV vaccine do not appear to be associated with vaccination 2
  • Case reports have linked HPV vaccination with new onset chronic conditions, including autoimmune diseases, but well-conducted population-based studies show no association 2

Comparison of HPV Vaccines

  • The bivalent HPV vaccine (Cervarix) has been associated with more adverse effects, including pain, swelling, and redness, compared to the quadrivalent HPV vaccine (Gardasil) 3
  • The quadrivalent HPV vaccine has been associated with more general symptoms, such as fatigue and fever, compared to the bivalent vaccine 3

Serious Adverse Events

  • Two large randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study, including deaths and serious systemic adverse events 5
  • The number needed to vaccinate and the number needed to seriously harm have been calculated for the 9-valent HPV vaccine, highlighting the importance of ongoing safety assessment 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review.

The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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