Questions about HPV Vaccine Safety

Safety Monitoring for HPV Vaccines

All vaccines used in the United States are required to go through years of extensive safety testing before they are approved and licensed by the U.S. Food and Drug Administration (FDA). After vaccines are licensed, CDC and FDA continue to monitor for any rare or new problems that may happen after vaccination.

CDC uses three systems to monitor the safety of vaccines after they are licensed:

Learn more about the vaccine safety monitoring systems and how these systems work together to protect America’s health

About VAERS, reported adverse events, and safety data

The Vaccine Adverse Event Reporting System (VAERS) is a national vaccine safety monitoring system co-managed by CDC and FDA. The system accepts reports of adverse events following vaccination from vaccine manufacturers, healthcare professionals, and the public. It serves as an early warning system to detect possible safety problems that require further evaluation; however, the safety data the system provides has limitations.

VAERS data limitations include reporting biases, inconsistent data quality and completeness, and a lack of unvaccinated comparison groups. Because of these limitations, VAERS generally cannot determine if a vaccine caused a reported adverse event. While some reported adverse events may be caused by vaccination, others may be coincidental and not related to vaccination. Learn more about VAERS and the safety data it provides.

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.

Among all reports to the Vaccine Adverse Event Reporting System (VAERS) following HPV vaccines, the most frequently reported symptoms overall were:

  • Dizziness
  • Fainting
  • Headache
  • Nausea
  • Fever
  • Pain, redness, and swelling in the arm where the shot was given

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.


Gardasil 9
®
Gardasil 9 is currently the only HPV vaccine available in the United States. From its licensure in December 2014 through December 2017, over 28 million doses of Gardasil 9 have been distributed in the U.S. During the same period, VAERS received 7,244 U.S. reports of adverse events following Gardasil 9 vaccination. Overall, 97% of reports were classified as non-serious reports; 3% have been classified as serious.

Gardasil®
From its licensure in June 2006 through December 2017more 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.

Cervarix®
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.

Which adverse events are considered “serious”?

By regulation, an adverse event is defined as seriousexternal icon if it involves any of the following outcomes:

  • death
  • a life-threatening adverse event
  • a persistent or significant disability or incapacity
  • a congenital anomaly or birth defect
  • hospitalization, or prolongation of existing hospitalization

Some deaths among people who received an HPV vaccine have been reported to the Vaccine Adverse Events Reporting System (VAERS). This does not mean that the vaccine caused the death, only that the death occurred after the person got the vaccine. CDC and FDA investigate all reports of death following vaccination.

Gardasil 9
From December 1, 2014 through December 31, 2017, when about 28 million doses of Gardasil-9 had been distributed in the United States, VAERS received 7 reports of death. Among these reports, only 2 were verified through medical record review, autopsy reports or death certificates. The other reports were considered hearsay (based on secondhand information), meaning there was not enough information to confirm whether the death occurred.

Gardasil
Also, from June 2006 through December 2017, when about 80 million doses of HPV vaccine had been distributed in the United States, VAERS received 183 reports of death after people received Gardasil. Among the 183 reports of death, CDC researchers were able to review medical records, autopsy reports or death certificates among 67 reports and verified that the person had died. The remaining 116 reports could not be further studied because there was not enough information included in the report to verify that a person had died.

After careful review of every reported death that has happened after Gardasil or Gardasil-9 vaccination, CDC concluded there was no pattern of death occurring with respect to time after vaccination, and there was no consistent vaccine dose number or combination of vaccines given among the reports. In summary, the evidence did not suggest a causal link between Gardasil and the reported deaths.

The Vaccine Safety Datalink (VSD) also conducted a study evaluating death 30 days following Gardasil. After a review of all the participating health plans’ data to identify death occurring 0-30 days after Gardasil vaccination, there were 13 deaths identified of which 9 were due to external causes such as accident, homicide, or suicide. Of the 4 remaining deaths, two were determined unrelated to vaccination and the other two did not have sufficient evidence to confirm or rule out whether Gardasil caused the death. In analyses that included comparisons of the rate of death following Gardasil in this study to national rates of death for all causes in the United States, the risk of death was not increased during the 30 days following vaccination and no deaths were found to be causally associated with vaccination after clinical review. Read the published article, “Vaccination and 30-day Mortality Risk in Children, Adolescents, and Young Adults.”external icon

Yes. When fainting (or syncope) 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.

General HPV Vaccine Safety

Yes. The safety of HPV vaccine has been well studied. All three HPV vaccines went through years of extensive safety testing before it was licensed by the FDA, which only licenses a vaccine if it is safe, effective, and the benefits outweigh any risks.

  • Gardasil 9 was studied in more than 15,000 women and men.
  • Gardasil was studied in 29,000 women and men.
  • Cervarix was studied in more than 30,000 women.

After licensure, HPV vaccine safety monitoring by CDC and FDA continues to look for rare or new problems that may happen after vaccination. Since HPV vaccine became available in 2006, there have been many large safety studies conducted in the United States and other countries with reassuring findings. There have been no confirmed safety signals (i.e. higher than expected number of adverse events) observed, with the exception of syncope (fainting).

Fainting and related symptoms (such as jerking movements) can happen after any medical procedure, including vaccination. Some people, especially teens, faint after being vaccinated. To prevent fainting-related injuries, people receiving HPV vaccines should sit or lie down during vaccination, then patients should be observed for 15 minutes after receiving the shot.

Although rare, a severe allergic reaction called anaphylaxis can also occur following HPV vaccines.

CDC continues to monitor the safety of HPV vaccines and provides updates to the Advisory Committee on Immunization Practices (ACIP), as well as the World Health Organization’s Global Advisory Committee for Vaccine Safety (GACVS). See an overview of CDC’s vaccine safety publications.

Gardasil 9 is the only HPV vaccine currently available for use in the United States.

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.

Vaccines, like any medicine, can have side effects. Some people who get an HPV vaccine have no side effects at all. Some people report having mild side effects, like a sore arm from the shot for a day or two. The most common side effects are usually mild and go away on their own.

Common side effects of HPV vaccine:

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

Some people should not get HPV vaccine (Gardasil 9) or should wait.

  • Anyone who has ever had a life-threatening allergic reaction to any component of HPV vaccine, or to a previous dose of HPV vaccine, should not get the vaccine. Anyone with severe allergies, including an allergy to yeast, should talk to their doctor before getting the vaccine.
  • HPV vaccine is not recommended for pregnant women. However, receiving HPV vaccine when pregnant is not cause for alarm. Women who are breastfeeding may get the vaccine.
  • People who are mildly ill (low-grade fever of less than 101 degrees, a cold, runny nose, or cough) when a dose of HPV vaccine is planned can still be vaccinated. People with a moderate or severe illness should wait until they are better.

If you or your child has a severe allergic reaction or other health emergency, call 9-1-1 or go to the nearest hospital.

Look for any signs or symptoms that concern you, such as signs of a severe allergic reaction, very high fever, or behavior changes. Signs of a severe allergic reaction can include hives, swelling of the face and throat, difficulty breathing, a fast heartbeat, dizziness, and weakness. These would start a few minutes to a few hours after the shot is given.

After seeing a doctor, the reaction should be reported to the Vaccine Adverse Event Reporting System (VAERS). This system is used to report any side effect or adverse event following vaccination. Your doctor can file this report, or you can do it yourself through the VAERS website or by calling 1-800-822-7967.

Reproductive Concerns

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. There is no current evidence that HPV vaccines cause reproductive problems in women.

What is primary ovarian insufficiency (POI)?

Also known as “premature menopause,” this is a condition in which a woman’s ovaries stop functioning before age 40. Causes of primary ovarian insufficiency include:

  • Genetics
  • Chemicals in the environment
  • Cancer treatments
  • Cigarette smoking
  • Autoimmune disorders
  • Some viral infections

However, in many cases it’s not possible to determine the cause. CDC and FDA have not found any proof that HPV vaccines cause POI.

How has CDC and FDA addressed the concern of HPV vaccines and POI?

As part of ongoing safety monitoring of HPV vaccines, CDC has reviewed reports of POI to VAERS following both Gardasil 9 and Gardasil vaccination. CDC has also conducted additional safety research on HPV vaccine in the VSD.

Gardasil 9
Between December 1, 2014 and Dec 31, 2017, when 28 million doses of Gardasil 9 had been distributed in the United States, VAERS received 3 reports of POI following Gardasil 9 vaccination. The 3 reports were determined to be hearsay reports (based on secondhand information), meaning there was not enough information to confirm a diagnosis of POI.

Gardasil
Between January 2009 and December 2015, more than 60 million doses of Gardasil were distributed for use in the United States. During this time period, VAERS received 17 reports of POI following Gardasil vaccination. Two of these reports had a physician diagnosis of POI; the remaining 15 reports were considered hearsay reports (based on secondhand information), meaning there was not enough information to confirm the diagnosis. Read the published article, “Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015external icon.

FDA and CDC reviewed the confirmed POI reports, investigating whether or not there was a pattern that might indicate the vaccine was causing the problem. There were no patterns found, making it unlikely the vaccine was the cause.

CDC’s Clinical Immunization Safety Assessment Project (CISA) also reviewed current literature regarding HPV vaccines and POI. The review found that the current evidences is insufficient to suggest or support that HPV vaccinations cause POI. Read the published review, “Primary Ovarian Insufficiency and Human Papilloma Virus Vaccines: A Review of the Current Evidence.”external icon

To examine this issue further, CDC conducted a VSD study of reports of POI following adolescent vaccination, including HPV vaccination among girls 9-26 years of age. Among 199,078 girls followed, only one confirmed case of POI was identified where the patient received HPV vaccine. This patient received HPV vaccine 23 months before her first clinical evaluation of having a delayed first period. Overall, the study found no increased risk of POI following HPV vaccination or any adolescent vaccination. Read the published article, “Primary Ovarian Insufficiency and Adolescent Vaccinationexternal icon.

CDC and FDA continue to closely monitor the safety of HPV vaccines.

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 Resourcesexternal icon

AAFP HPV Vaccine Summaryexternal icon

ACOG HPV Guidelines and Recommendationsexternal icon

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.

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. If 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 Registriesexternal icon 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).

As part of ongoing safety monitoring of HPV vaccines, CDC has monitored pregnancy outcomes for women who were mistakenly given HPV vaccines during their pregnancies. Both VAERS and the VSD have supported these efforts:

Gardasil 9

From December 2014 through December 2017, when approximately 28 million doses of Gardasil-9 were distributed in the United States, VAERS received 82 reports of pregnant women vaccinated with Gardasil 9; 60 reports did not describe an adverse event and were submitted only to report the occurrence. Of those reporting an adverse event, the most frequently reported were miscarriage and injection site reactions (three reports each; 3.7%). The observed number of VAERS reports of miscarriages were not considered to be unusual as miscarriage may occur in up to 1/3 of all pregnancies. Injection site reactions after vaccination, such as soreness or swelling where the shot was given, are the most common side effects. They are usually mild and go away on their own. Overall, researchers found no unexpected patterns of adverse event reporting. Read the published article, “Safety of 9-valent human papillomavirus vaccine administration among pregnant women: Adverse events reported in the Vaccine Adverse Event Reporting System (VAERS), 2014-2017external icon.”

Gardasil

In a review of reports to VAERS between June 2006 and December 2013, there were 147 reports of Gardasil administered to pregnant women. There were no unexpected patterns of adverse events in developing babies, nor were there any reported maternal or infant deaths. The most frequent adverse event reported was fever. Read the published article, “Safety of quadrivalent human papillomavirus vaccine (Gardasil) in pregnancy: adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006-2013external icon.

VSD conducted a study evaluating the risk of miscarriage after inadvertent Gardasil vaccination of pregnant women. Between 2008 and 2014, 2,800 pregnancies with Gardasil exposure were identified. Researchers found that inadvertent Gardasil exposure before and during pregnancy was not significantly associated with an increased risk of miscarriage. Read the published article, “Risk of Spontaneous Abortion After Inadvertent Human Papillomavirus Vaccination in Pregnancyexternal icon.

VSD also conducted a study looking at maternal and infant outcomes following Gardasil vaccination of women who were mistakenly vaccinated while pregnant. Between 2007 and 2013, 720 women received Gardasil at some point two weeks before their last menstrual cycle or two weeks after, and 638 women were mistakenly given Gardasil while pregnant. Administration of Gardasil during pregnancy or right before becoming pregnant was not associated with adverse pregnancy or birth outcomes. Read the published article, “Maternal and Infant Outcomes After Human Papillomavirus Vaccination in the Periconceptional Period or During Pregnancyexternal icon.

Other Medical Concerns

Guillain-Barré syndrome (GBS) is a rare disorder where a person’s own immune system damages nerve cells, causing muscle weakness and sometimes paralysis. Most people recover fully from GBS, but some experience long-term nerve damage.

Gardasil 9

The Vaccine Adverse Event Reporting System (VAERS) continually monitor reports of GBS following Gardasil 9. Between December 1, 2014 and December 31, 2017, when approximately 28 million doses of Gardasil 9 had been given out in the United States, there were 4 confirmed reports of GBS. Read the article “Safety monitoring of 9-valent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS).external icon

The Vaccine Safety Datalink (VSD) also monitored for GBS following Gardasil 9 vaccination. Between October 2015 through October 2017, in VSD nearly 840,000 doses of Gardasil 9 were administered and researchers did not find a safety signal of GBS after HPV vaccination. Read the article, “Near Real-Time Surveillance to Assess the Safety of the 9-valent Human Papillomavirus Vaccineexternal icon.”

Gardasil
VSD conducted monitoring for GBS following Gardasil vaccination from August 2006 to December 31, 2015. During this time, 2,773,185 doses of Gardasil were administered to males and females aged 9-26 years. Using medical records to confirm cases of GBS, there was 1 GBS case in a male. The study provides evidence that the risk of getting GBS following HPV vaccination is extremely rare. Read the published article, “Risk of Guillain-Barré Syndrome following quadrivalent human papillomavirus vaccine in the Vaccine Safety Datalink.external icon

POTS is a condition that causes lightheadedness or fainting and a rapid increase in heartbeat upon standing. The cause is unknown, but doctors think POTS may be associated with a number of risk factors and syndromes, including recent viral illness, head trauma, physical deconditioning, and nervous system problems.

Gardasil 9, Gardasil, and Cervarix
From June 2006 through August 2015, more than 80 million HPV vaccine doses were distributed in the United States. During this time period, VAERS received 29 reports of POTS following HPV vaccination. Of these reports, 28 followed Gardasil vaccination, which accounted for the majority of HPV vaccinations in the United States during this time period. CDC’s safety review did not detect any unusual or unexpected patterns among the cases. Read the published article, “Reports of Postural Orthostatic Tachycardia Syndrome After Human Papillomavirus Vaccination in the Vaccine Adverse Event Reporting System.external icon

In November 2015, the European Medicine’s Agency completed a detailed review of available POTS data from young women who received HPV vaccines. The review found that the evidence does not support a causal link between HPV vaccines and POTS. Read the published article, “Review concludes evidence does not support that HPV vaccines cause CRPS or POTSpdf iconexternal icon.”

Ongoing safety monitoring through VAERS has not detected any safety concerns related to POTS following HPV vaccination.

VAERS has also conducted a formal review of POTS following Gardasil 9 vaccination. Between December 1, 2014 and December 31, 2017, when over 28 million doses of Gardasil 9 had been given out in the United States, VAERS received 17 reports of POTS. Among those, 6 reports partially met diagnostic criteria of POTS.

The Vaccine Safety Datalink (VSD) is currently conducting a study to describe POTS among 9 to 30 year-olds who received any adolescent vaccination.

Some people who get the HPV vaccine may have some pain in the arm where the shot was given. Usually this pain is mild and goes away quickly. Swelling and redness also sometimes occur after HPV vaccination.

CDC is aware of reports (in Japan and elsewhere) of chronic pain following HPV vaccines. Some of these reports were described as potential cases of Complex Regional Pain Syndrome (CRPS), a rare condition of persistent pain that usually affects arms, legs, hands, or feet after an injury or trauma to that limb.

Gardasil 9, Gardasil, and Cervarix

CDC reviewed reports to VAERS of CRPS following Gardasil 9 vaccination between December 1, 2014 and December 31, 2017. Of the 7,244 reports following HPV vaccination, there was 1 report of CRPS; however, because of incomplete information, the report could only be classified as “possible CRPS.”

A safety review of reports to VAERS from June 2006 through July 2015 identified 22 reports of CRPS following HPV vaccination. At that time, over 67 million doses of HPV vaccine had been distributed in the United States. The findings included 21 reports of CRPS following Gardasil vaccination and 1 report following Cervarix vaccination. The review concluded that CRPS following HPV vaccination is rare. Read the published article, “HPV Vaccination and Complex Regional Pain Syndrome: Lack of Evidenceexternal icon.
In November 2015, the European Medicine’s Agency completed a detailed review of available data on CRPS in young women who received HPV vaccines. The review found that the evidence does not support a causal link between HPV vaccines and CRPS. Read the published article, “Review concludes evidence does not support that HPV vaccines cause CRPS or POTSpdf iconexternal icon.

The Vaccine Safety Datalink (VSD) is currently conducting  a study to describe CRPS among 9 to 30 year-olds who received any adolescent vaccination.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness. People with ME/CFS have overwhelming fatigue that is not improved by rest. While researchers have not yet identified a cause of ME/CFS, some symptoms can be treated or managed. CDC is aware of reports of chronic fatigue syndrome following HPV vaccines and continues to monitor for any unusual or unexpected patterns among reported cases.

The Vaccine Safety Datalink (VSD) is currently conducting a study to describe CFS among 9-36 year-olds who received any vaccination.

Gardasil
In a review of reports to the Vaccine Adverse Event Reporting System (VAERS) between June 2006 and September 2015, there were 20 reports of ME/CFS following Gardasil vaccination. At that time, over 80 million doses of Gardasil had been distributed in the United States. No unusual or unexpected patterns of reporting of CFS following HPV vaccine were detected.

In addition, a 2017 study published by the Norwegian Institute of Public Health observed no increased risk of ME/CFS among girls given HPV vaccine through the Norwegian national immunization program between 2009 and 2014. Read the published article, “HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norwayexternal icon.

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