Human Papillomavirus (HPV) Vaccine Safety

Key points

  • Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States.
  • Some HPV infections can be persistent and can progress to cancer in both women and men later in life.
  • There is a vaccine that can prevent the infections that most commonly cause cancer.

Overview

Human papillomavirus (HPV) is spread through intimate skin-to-skin contact. HPV infections are so common that nearly all men and women will get at least one type of HPV at some time in their lives. HPV infections that do not go away can cause:

  • Cervical, vaginal, and vulvar cancers (in women).
  • Penile cancer (in men).
  • Anal cancer.
  • Cancer of the back of the throat (oropharynx).
  • Genital warts.

CDC is aware of public concern about the safety of HPV vaccine. Since the vaccine's introduction in 2006, vaccine safety monitoring and studies conducted by CDC, FDA, and other organizations have documented a reassuring safety record.

Available vaccines & manufacturer package inserts

Gardasil 9 and manufacturer insert

  • Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant; 9vHPV) was approved by FDA for use in 2014.
  • The safety of Gardasil 9 was studied in clinical trials with more than 15,000 participants before it was licensed and continues to be monitored.
  • Gardasil 9 protects against 9 types of cancer-causing HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

For HPV vaccine to be most effective, the series should begin prior to exposure to HPV.

Keep Reading: Vaccine Information Statement

While only 9vHPV has been available for use in the U.S. since late 2016, safety studies of 4vHPV (Gardasil) have provided important safety information relevant for 9vHPV. Both 9vHPV and 4vHPV are manufactured using a similar process, and contain 4 of the same antigens: HPV types 6, 11, 16, and 18. The 9vHPV vaccine adds 5 additional antigens, providing protection against 9 types of cancer-causing human papillomaviruses. Studies of 2vHPV (Cervarix) have also shown a favorable safety profile. While the vaccines target different HPV types, all three HPV vaccines are similar and made from a single protein of the HPV virus.

Who should & should not get the vaccine

CDC recommends HPV vaccination for everyone through age 26 years, if not vaccinated already. Teens and young adults who start the series at ages 15 through 26 years still need three doses of HPV vaccine. Three doses are also recommended for people with certain immunocompromising conditions ages 9 through 26 years.

Keep Reading: Who should & should not get the vaccine

Common side effects

  • Pain, redness, or swelling in the arm where the shot was given.
  • Fever.
  • Headache or feeling tired.
  • Nausea.
  • Muscle or joint pain.

When to call 911‎

Severe allergic reactions following vaccination are rare, but can be life threatening. If someone experiences symptoms of a severe allergic reaction, which can include hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, and weakness.

HPV vaccine is safe and effective at preventing HPV-related infections and cancers. Vaccines, like any medicine, can have side effects. Many people who get the HPV vaccine have no side effects at all. The most common side effects are usually mild, like a sore arm from the shot.

Report possible adverse events to VAERS‎
‎

The Vaccine Adverse Event Reporting System (VAERS) is an early warning system, co-managed by CDC and FDA, that monitors for potential vaccine safety problems. Healthcare providers and vaccine manufacturers are required by law to report certain adverse events (any side effect or health problem after vaccination that is concerning to you, even if you are not sure if the vaccine caused the event) following vaccination to VAERS; patients and caregivers can also submit reports.
Submitting a Vaccine Adverse Event Reporting System (VAERS) Report and Using VAERS Data

Reproductive concerns

HPV vaccines and primary ovarian insufficiency (POI)

Also known as "premature menopause," POI is a condition in which a woman's ovaries stop functioning before age 40.

Fact‎

CDC and FDA have not found any proof that HPV vaccines cause reproductive problems in women, including POI.123

HPV vaccines and fertility

HPV vaccination prevents infection with the HPV types that most commonly cause cervical cancer. In some cases, women develop cervical cancer before starting or finish having children. Treatment for cervical cancer (removal of the cervix and uterus, chemotherapy, and/or radiation) can keep a woman from being able to become pregnant. Preventing cervical cancer through HPV vaccination reduces this risk.

CDC works closely with the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) on HPV vaccination. Both organizations have information about HPV vaccine available on their websites. Also, the American College of Obstetrics and Gynecologists (ACOG) offers additional resources.

AAP HPV Vaccine Tools and Resources
AAFP HPV Vaccine Summary
ACOG HPV Guidelines and Recommendations

HPV vaccines and pregnancy

HPV vaccines are not approved or recommended for pregnant women. However, some pregnant women receive HPV vaccines because they don't know that they are pregnant at the time of vaccination, or otherwise receive an HPV vaccine when they shouldn't have.

Fact‎

CDC and vaccine manufacturers have monitored and studied HPV vaccine safety in women who received the vaccine when they were pregnant. The manufacturers for each vaccine have established pregnancy registries to follow outcomes for those women who were mistakenly vaccinated. Close monitoring has not found any health concerns. 4567If a woman receives HPV vaccine and later learns that she is pregnant, there is no reason to be alarmed.

Any woman who learns she was pregnant at the time she received an HPV vaccine is encouraged to contact the vaccine manufacturer. This will help us learn how pregnant women respond to the vaccine.

  • If a pregnant woman receives a dose of Gardasil 9 no intervention is needed. If she found out she was pregnant when starting the vaccination series, the remainder of the 3-dose series should be delayed until completion of pregnancy. She may contact Merck at 1-877-888-4231 if she has questions related to getting the vaccine while pregnant.
  • Doctors should report Gardasil 9 vaccination during pregnancy as early in the pregnancy as possible using the Merck Pregnancy Registries or calling 1-800-986-8999.
  • Pregnant women who received Gardasil 9 and their physician can also report to the Vaccine Adverse Event Reporting System (VAERS).

A closer look at the safety data

HPV vaccines are safe‎

Findings from many vaccine safety monitoring systems and more than 160 studies have shown that HPV vaccines have a favorable safety profile—the body of scientific evidence overwhelmingly supports their safety.

Of the reports to VAERS, 6% were classified as "serious." Of the other reports to VAERS relating to HPV, about 22% of the reports were not related to health problems, but were reported for reasons such as improper vaccine storage or the vaccine being given to someone for whom it was not recommended.

Over 100 million doses of HPV vaccines were distributed in the United States from June 2006 through December 2017. To date, most of CDC’s HPV vaccine safety monitoring and research has focused on Gardasil because it has accounted for the majority of HPV vaccine doses distributed in the United States. These safety efforts continue, now focusing on Gardasil 9.

Gardasil 9, Gardasil and Cervarix

  • In November 2019, initial post-licensure safety monitoring of Gardasil 9 was published in Pediatrics. In two separate articles, analyses from the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) were presented. Both included multiple years of data, and did not identify any unexpected safety problems with Gardasil 9. These findings support the favorable safety profile that was established in pre-licensure clinical trials.
    • Analysis from VSD: The Vaccine Safety Datalink conducted near-real time surveillance from October 2015 through October 2017, looking at 11 pre-specified adverse events. During this two-year time period, nearly 840,000 doses were administered to people aged 9-26 years at six VSD sites. No new safety concerns were identified.8
    • Analysis from VAERS: Researchers reviewed 7,244 reports submitted to the Vaccine Adverse Event Reporting System following HPV vaccination from December 2014 through December 2017. Of those reports, around 97% were classified as non-serious; around 3% were considered serious. The analysis did not detect any new or unexpected safety concerns.9
  • In 2014, before Gardasil 9 was licensed by the FDA, its safety was evaluated across seven studies. The safety findings from these pre-licensure studies show that Gardasil 9 has a similar safety profile to Gardasil, an earlier version of the vaccine. The main findings from these studies:
    • The most common side effect reported was pain, swelling, and redness in the arm where the shot was given.
    • These mild side effects may occur more often after Gardasil 9 vaccination than after Gardasil. Women and girls who received Gardasil 9 reported higher rates of swelling and redness where the shot was given than those who received Gardasil. Reports of swelling and redness also increased with each following dose for those receiving Gardasil 9.
  • From its licensure in June 2006 through December 2017 more than 80 million doses of Gardasil were distributed in the United States. During the same period, VAERS received 36,142 U.S. reports of adverse events following Gardasil vaccination. Overall, 93% were non-serious reports; 7% have been classified as serious. Gardasil is no longer available in the United States.
    • Although rare, fainting was found to happen after HPV vaccination. In response, FDA changed Gardasil's guidance for doctors to include information about preventing falls and injuries from fainting. CDC and the Advisory Committee on Immunization Practices included this guidance in the recommendations for HPV vaccination. Based on these recommendations, healthcare professionals should administer HPV vaccinations while the patient is seated or lying down.
    • The patient should then remain seated and be observed for 15 minutes. CDC continues to remind doctors and nurses to observe this guidance and to share this information with all their patients.
  • In 2014, CDC published a report analyzing health events reported to VAERS following Gardasil vaccination from June 2006 through March 2014. About 92% of the Gardasil reports were classified as non-serious. The most common adverse events reported were:: syncope (fainting); dizziness; nausea; headache; fever; and injection site reactions (pain, swelling, and redness).
  • In 2014, CDC published a report analyzing health events reported to VAERS following Gardasil vaccination from June 2006 through March 2014. About 92% of the Gardasil reports were classified as non-serious. The most common adverse events reported were:: syncope (fainting); dizziness; nausea; headache; fever; and injection site reactions (pain, swelling, and redness).10
  • From its licensure in October 2009 through December 2017, about 720,000 doses of Cervarix were distributed in the United States. During the same period, there have been 245 U.S. VAERS reports of adverse events following Cervarix vaccination. Overall, 96% were non-serious reports; 4% have been classified as serious.
    • Cervarix is no longer available in the United States.

Fainting and anaphylaxis

  • Syncope (fainting) may be caused by injected vaccines, including HPV vaccines. 1011
    • When fainting was found to happen after vaccination, FDA changed Gardasil’s guidance for doctors to include information about preventing falls and injuries from fainting after HPV vaccination. CDC and the Advisory Committee on Immunization Practices included this guidance in the recommendations for HPV vaccination. CDC continues to remind doctors and nurses to observe this guidance and to share this information with all their patients.
  • Very rarely, any vaccine, including HPV vaccine, can cause anaphylaxis. Some people are allergic to certain ingredients in vaccines. As recommended by ACIP, people who experienced a severe allergic reaction (e.g., anaphylaxis) to a previous vaccine dose or to a vaccine component, including yeast, should not receive the HPV vaccine.11

Guillain-Barré syndrome (GBS)

  • The risk of getting GBS following HPV vaccination is extremely rare.121314

Postural orthostatic tachycardia syndrome (POTS)

  • POTS is a condition that causes lightheadedness or fainting and a rapid increase in heartbeat upon standing.
  • Ongoing safety monitoring has not detected any safety concerns related to POTS following HPV vaccination.1415
  • The Vaccine Safety Datalink (VSD) is currently conducting a study to describe POTS among 9 to 30 year-olds who received any adolescent vaccination.

Complex Regional Pain Syndrome (CRPS)

  • CRPS is a rare condition of persistent pain that usually affects arms, legs, hands, or feet after an injury or trauma to that limb.
  • Evidence does not support a causal link between HPV vaccines and CRPS.1617

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

  • Chronic fatigue syndrome (ME/CFS) is a disabling and complex illness.
  • The Vaccine Safety Datalink (VSD) is currently conducting a study to describe CFS among 9-36 year-olds who received any vaccination.
  • Studies show no increased risk of ME/CFS among girls given HPV vaccine.15

Death

  • Evidence does not suggest a causal link between Gardasil and death.18

Gardasil HPV vaccine recall (2013) FAQs

Why was there a recall of the Gardasil HPV vaccine?

On December 16, 2013 CDC was informed by Merck that the company planned to implement a voluntary recall of one lot (lot J007354) of Gardasil [Human Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine, Recombinant], due to the potential for a small number of vials to contain glass particles as a result of breakage during the manufacturing process. These vials were distributed between August 20, 2013, and October 9, 2013. No other lots were affected.

If my child received one of the affected HPV vaccine vial injections, what could happen?

If a vaccine containing glass particles (tiny enough to get through a needle) is given to a patient, mild reactions routinely seen after vaccination may occur (for instance, redness or swelling at the injection site). There are multiple safety systems in this country that track and monitor vaccine safety, including the Vaccine Adverse Event Reporting System (VAERS), which allows anyone to report a possible vaccine side effect (also called "adverse event"). To date, no adverse events related to this lot of HPV vaccine have been reported other than mild reactions such as redness and swelling at the injection site. It is not expected that delayed side effects will occur.

If my child received the HPV vaccine injection from this affected lot, does he or she have to be vaccinated again?

If your child received HPV vaccination from this one affected lot, he or she does NOT have to be vaccinated again. The vaccine's effectiveness is not impacted by this problem. The HPV vaccine series is given in 3 shots over 6 months. Be sure that your child gets all 3 shots for full protection.

How will I know if my child received one of the affected HPV vaccinations?

Merck is currently contacting its direct customers (doctors' offices or clinics) who have purchased or received product from the affected lot. People who have recently received an HPV vaccine, including those who received vaccine from the affected lot, do not need to take any action as a result of this recall. Because no action is necessary, CDC is not asking doctors to notify patients who have received vaccine from the affected lot. However, if you want to know if your child received a dose of vaccine from the affected lot, you can ask his or her doctor.

How do I find out more information about this voluntary recall?

Hotline information‎

For questions about this recall or to report any adverse events following vaccination, please contact: Merck National Service Center at 800-444-2080.

Does CDC recommend HPV vaccination?

Yes. This recall was caused by an isolated problem in the vaccine manufacturing process. HPV vaccine continues to have a strong safety record, and CDC continues to recommend that all preteen girls and boys receive three doses of this cancer-preventing vaccine at age 11 or 12 years.

How CDC monitors vaccine safety

CDC and the Food and Drug Administration (FDA) are committed to ensuring that vaccines provided to the public are safe and effective. Once vaccines are licensed or authorized for emergency use in the United States, CDC and FDA continuously monitor them through several safety systems.

Keep Reading: About CDC's Vaccine Safety Monitoring Program

Resources

Who Should NOT Get Vaccinated with these Vaccines?
Who should NOT Get Vaccinated?
Human Papillomavirus (HPV) ACIP Vaccine Recommendations
ACIP Recommendations on HPV and other MMWR articles. Advisory Committee on Immunization Practices (A...
Contraindications and Precautions
Contraindications and Precautions: General Best Practice Guidelines for Immunization. Advisory Commi...
Immunization Schedules
Stay up-to-date on getting recommended vaccines. Here are immunization schedules for people of all a...
Vaccine & Immunization Information for Health Care Providers
CDC vaccine and vaccination information for U.S. health care providers.
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Content Source:
National Center for Emerging and Zoonotic Infectious Diseases (NCEZID)
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