HPV Vaccine Safety and Effectiveness Data

More than 15 years of monitoring and research have accumulated reassuring evidence that human papillomavirus (HPV) vaccination provides safe, effective, and long-lasting protection against cancers caused by HPV infections.

Data from Clinical Trials

Each HPV vaccine—9-valent HPV vaccine (Gardasil® 9), quadrivalent HPV vaccine (Gardasil®), and bivalent HPV vaccine (Cervarix®)—went through years of strict safety testing before the U.S. Food and Drug Administration (FDA) licensed it. Each vaccine was found to be safe and effective in clinical trials.

Gardasil 9 was studied in clinical trials with more than 15,000 females and males.

Gardasil was studied in clinical trials with more than 29,000 females and males.

Cervarix was studied in clinical trials with more than 30,000 females.

Since late 2016, Gardasil 9 has been the only HPV vaccine available for use in the United States.

Vaccine Safety Monitoring Data

With more than 135 million doses of HPV vaccines distributed in the United States, there are robust data showing that HPV vaccines are safe.

Like any vaccine or medicine, HPV vaccines can cause side effects. The most common side effects reported through CDC’s Vaccine Adverse Event Reporting System (VAERS) are pain, redness, or swelling in the arm where the vaccine was given, dizziness, syncope (fainting), nausea, and headache.
With the exception of syncope, which is more common among adolescents after receiving any vaccine, there have been no confirmed adverse events occurring at higher than expected rates following HPV vaccination.
On very rare occasions, a person may have a serious allergic reaction (anaphylaxis) to any vaccine, including HPV vaccines. In the United States, anaphylaxis following vaccination has a reported rate of 3 cases per 1 million doses administered. People with severe allergies to any component of a vaccine should not receive that vaccine.

Vaccine Safety Monitoring in the United States

The United States monitors safety of all vaccines through several systems:

Vaccine Adverse Events Reporting System (VAERS) is a spontaneous reporting system that serves as an early warning system to detect possible safety problems that may be related to vaccination. Anyone can submit a report to VAERS. However, it is generally not possible to find out from VAERS data if a vaccine caused the adverse event, and the reports often lack details and sometimes contain errors.
Vaccine Safety Datalink (VSD) is a collaborative project between CDC and eight healthcare organizations that monitors the safety of vaccines and conducts rigorous vaccine safety assessments.
Clinical Immunization Safety Assessment Project (CISA) conducts vaccine safety clinical research and assesses complex clinical adverse events following vaccination.

While only Gardasil 9 has been available for use in the United States since late 2016, safety studies of Gardasil have provided important safety information relevant for Gardasil 9 (Gardasil and Gardasil 9 are similar types of vaccines and are produced by the same manufacturer). Studies of Cervarix have also shown a favorable safety profile. While the vaccines prevent infections with some different HPV types, all three HPV vaccines are similar, and based on a single protein of the human papillomavirus.

What is an adverse event?

An “adverse event” is any health problem that happens after a shot or other vaccine. An adverse event might be truly caused by a vaccine, or it might be pure coincidence.
An adverse event is defined by law as “serious” if it is life-threatening or results in death, a persistent or significant disability or incapacity, congenital anomaly or birth defect, hospitalization, or prolongation of existing hospitalization.
VAERS data alone usually cannot be used to answer the question, “Does a certain vaccine cause a certain adverse event?” This is mainly because adverse events reported to VAERS may or may not be caused by vaccines.
VAERS reports help provide medical professionals at CDC and FDA with a signal of a potential adverse event that needs to be studied further.

Data on Gardasil 9 (9vHPV)

VAERS (data from December 2014 through December 2017)(1)
- Approximately 28 million doses of Gardasil 9 distributed in the United States
- 7,244 reports of adverse events (AEs)
- 97% of AEs classified as non-serious and 3% classified as serious*
VSD (data from October 2015 and October 2017)(2)
- Weekly analyses to detect associations between Gardasil 9 administration and pre-specified adverse events (anaphylaxis, allergic reaction, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism) among males and females age 9–26 years from seven VSD sites
- >838,991 doses of Gardasil 9
- No statistically significant risk was detected for any of the pre-specified AEs following Gardasil 9 vaccination.

Data on Gardasil (4vHPV)

VAERS (data from June 2006 through December 2017)
- >80 million doses distributed in the United States
- 36,142 reports of adverse events (AEs)
- 93% of AEs classified as non-serious reports and 7% classified as serious*
VSD (data from August 2006 through October 2009)(3)
- Weekly analyses to detect associations between Gardasil administration and pre-specified AEs (Guillain–Barré syndrome, stroke, venous thromboembolism, appendicitis, seizures, syncope, allergic reactions, and anaphylaxis) among 9–26-year-old females from seven VSD sites
- >600,000 doses of Gardasil
- No statistically significant risk was detected for any of the pre-specified AEs following Gardasil vaccination.

Gardasil is no longer available in the United States.

Data on Cervarix (2vHPV)

VAERS (data from October 2009 through December 2017)(4)
- Approximately 720,000 doses of Cervarix distributed in the United States
- 245 reports of adverse events (AEs)
- 96% of AEs classified as non-serious and 4% classified as serious*

Cervarix is no longer available in the United States and was not administered at any of the VSD sites; therefore, no safety monitoring was conducted through the VSD network.

Vaccine Safety Studies of Specific Conditions

More than 160 studies have been conducted in multiple countries to look at whether specific adverse events can be linked to HPV vaccine.(5) These studies have shown HPV vaccines have a reassuring safety profile with no confirmed serious adverse events following vaccination.
Some studies have focused on specific outcomes such as venous thromboembolism, Guillain–Barré syndrome, and diabetes, while other studies have investigated multiple different health problems.(3, 6-23)

Complex Regional Pain Syndrome (CRPS)

VAERS (data from June 2006 through July 2015)
- >67 million doses of Cervarix and Gardasil distributed in the United States
- 21 reports of CRPS following Gardasil and one report following Cervarix out of the total 31,935 reports of adverse events following HPV vaccination in VAERS.(21) These 22 reports were not confirmed as CRPS cases.
VAERS (data from December 2014 through December 2017)
- Approximately 29 million doses of Gardasil 9 distributed in the United States
- One report of CRPS following Gardasil 9 identified out of the total 7,244 reports(1)
- As the information provided in VAERS was insufficient to confirm the diagnosis, the case was classified as “possible” CRPS

Postural Orthostatic Tachycardia Syndrome (POTS)

VAERS (data from June 2006 through July 2015)
- >84 million Gardasil doses distributed in the United States
- 13 confirmed cases of POTS following Gardasil identified out of the total 40,735 reports(24)
VAERS (data from December 2014 through December 2017) (1)
- Approximately 29 million doses of Gardasil 9 distributed in the United States
- 17 possible cases of POTS following Gardasil 9 identified out of the total 7,224 reports
- Six reports met clinical diagnostic criteria
- Remaining reports did not contain enough information to confirm a diagnosis of POTS

Primary Ovarian Insufficiency (POI)

VAERS (data from January 2009 through December 2015)
- >60 million doses of Gardasil distributed in the United States
- 17 reports of POI following Gardasil identified out of the total 19,760 reports(25)
- Two reports had a physician diagnosis of POI
- The remaining 15 reports were considered hearsay reports, meaning there was not enough information to confirm the diagnosis
- FDA and CDC reviewed the confirmed POI reports, investigating whether there was a pattern that might indicate the vaccine was causing the problem. No unusual or unexpected patterns were detected, making it unlikely the vaccine was the cause.
VSD conducted a study of POI following adolescent vaccinations, including HPV vaccination.
- Study included 199,078 females 9–26 years of age(18)
- 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

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

VAERS (data from June 2006 through September 2015)
- >80 million doses of HPV vaccine distributed in United States
- 20 reports of ME/CFS following Gardasil identified out of the total 40,735 reports
- No unusual or unexpected patterns of reporting ME/CFS following HPV vaccine were detected
A study from Norway found no increased risk of ME/CFS among girls aged 10–17 years who received Gardasil(10)
A study from Netherlands found no increased incidence of long-term fatigue among adolescent girls following introduction of Cervarix (19)
Two studies in Demark, one with over 300,000 vaccinated girls, showed no evidence of a causal link between Gardasil vaccination and diffuse autonomic symptoms. (26, 27)

Autoimmune Conditions

Several large studies have looked at whether HPV vaccines cause autoimmune disease. Many different autoimmune diseases have been studied, including Guillain–Barré syndrome, multiple sclerosis, and diabetes. To date, these studies have not found any association between HPV vaccination and autoimmune conditions.(6-9, 12-18, 20, 28)

Death

VAERS received seven reports of death following Gardasil 9 from December 1, 2014, through December 31, 2017, when about 29 million doses had been distributed in the United States.
VAERS also received 183 reports of death following Gardasil from June 2006 through September 2015, when about 80 million doses had been distributed.
With about 720,000 doses of Cervarix distributed in the United States, VAERS received no reports of death following this vaccine.
Five of the reported deaths for Gardasil 9 and 116 for Gardasil could not be further studied because there was not enough information included in the report to verify that a person had died.
Among the remaining reports, CDC reviewed medical records, autopsy reports, or death certificates and verified the person had died.
The review of available information did not suggest a causal link between HPV vaccines and the reported deaths.

Vaccine Effectiveness Studies

Studies in the United States and other countries have shown that HPV vaccination is already preventing cancer-causing infections, anogenital warts, and cervical precancers. Some data from other countries have found early evidence of a vaccine effectiveness against cervical cancer.

Monitoring HPV vaccine prevalence is ongoing in the United States. As early as 4 years after Gardasil licensure, vaccine-type HPV infections had decreased 56% among 14–19-year-old females.(29)
Within 12 years of vaccine introduction, infections with the four HPV types prevented by Gardasil decreased 88% among 14–19-year-old females and 81% among 20–24-year-old females in the United States.(30)

An analysis of healthcare claims data examined trends in anogenital warts among a large group of private health insurance enrollees in the United States. The study found that between 2006 (the first year HPV vaccination was recommended for females) and 2014, prevalence of anogenital warts among females decreased 61% among 15–19-year-olds and 44% among 20–24-year-olds.(31)
Small declines in males in these age groups were observed starting after 2009. The initial decline in males was likely due to herd effects, as routine vaccination of boys was recommended in 2011.

Compared to 2008–2009, cervical precancer rates among screened females in 2014–2015 were 50% lower in 18–20-year-olds and 36% lower in 21–24-year-olds.(32)
The percentage of cervical lesions due to HPV types prevented by HPV vaccination has dropped by 40% in vaccinated women since vaccines were introduced.(33)

Juvenile-onset recurrent respiratory papillomatosis is a rare but serious disease caused by HPV acquired at birth. JORRP has declined significantly in the United States since vaccination was introduced in 2006.(34)

Decreases in prevalence of vaccine-type HPV infections, anogenital warts, and cervical precancers have been observed in more than 14 countries with HPV vaccination programs, including Australia, Scotland, and others.(35)
In Sweden and Denmark, women who had been vaccinated in their teens have been shown to have a lower risk of cervical cancer as adults.(36, 37)

Duration of Protection Studies

Data from clinical trials and ongoing research show that HPV vaccination provides long-lasting protection.

Protection by HPV vaccination lasts for more than 10 years without becoming less effective.(38, 39, 40, 41)
Studies are ongoing to further evaluate the duration of protection.
No data indicate that the protection from HPV vaccination lessens over time.

HPV Vaccine Safety

HPV Vaccine Safety – FAQs

Fact Sheet: What Parents Should Know About HPV Vaccine Safety and Effectiveness

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