Human Papillomavirus (HPV)
- Human papillomavirus (HPV) is the most commonly sexually transmitted infection in the U.S. and there are more than 200 known HPV types, the majority of which are not harmful;1
- About 75% of HPVs have been associated with non-cancerous warts (papillomas) on the hands, chest, arms and feet, such as low-risk HPV types 6 and 11;2
- About 40 HPV types have been found in the mucosal surfaces of the cervix, vagina, vulva, anus, penis, mouth and throat, including the most common high-risk (cancer-causing) HPV types 16 and 18. High-risk HPV types are associated with development of cancer of the cervix and five other genital and oral cancers affecting women and men;3
- HPV infection is experienced by the majority of sexually active women and men and is naturally cleared from the body within two years by more than 90 percent of those who become infected4. Antibodies to the type of HPV that caused the infection remain in the body to help prevent future re-infection with that same HPV type;5
- Sometimes HPV infection does not clear from the body naturally and the infection becomes chronic.6
- Women who are chronically infected with HPV for many years and who don’t get pre-cancerous cervical lesions promptly identified and treated can develop cervical cancer and die.7
- High risk factors for developing HPV-related cancers include: smoking, multiple sexual partners, long-term oral contraceptive use, multiple births, weakened immune system, co-infection with Chlamydia or HIV, poor nutrition, heavy drinking and smoking, and chronic inflammation;8
- After Pap smear tests that screen for cancerous conditions became a routine part of gynecological health care for American women in the 1960’s, U.S. cervical cancer cases dropped by 75 percent.9 Women are recommended to get regular Pap tests throughout their life whether or not they get HPV vaccinations;10
- In 2014, there were 42,394 new HPV related cancer cases reported,11 which represents less than three percent of all cancers diagnosed in the U.S.12 and one one hundredth of a percent (.0001) of the U.S. population.13
- In 2015, the Centers for Disease Control (CDC) and National Institutes of Health (NIH) estimated that 12,845 American women were diagnosed with cervical cancer and that there were 4,175 related deaths.14
- The CDC currently recommends two doses of Gardasil 9,15 the only Food and Drug Administration (FDA) approved HPV vaccine currently available in the U.S. Gardasil 9, manufactured by Merck, was licensed in 2014 to prevent cervical, vulvar and anal cancers caused by high risk HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts caused by low risk HPV types 6 and 11; and precancerous lesions caused by all of these HPV types.16 The vaccine is approved for use by females and males ages 9 to 26 years.17 Two additional FDA approved HPV vaccines, Gardasil,18 the original HPV vaccine licensed in 2006, covering HPV types 6, 11, 16, and 18, and Cervarix vaccine,19 licensed in 2009, covering HPV types 16 and 18 are currently not available in the U.S.
- Merck’s original Gardasil vaccine was studied for less than two years in about 1,200 girls under age 16 before it became the first U.S. licensed HPV vaccine. Prior to licensure, Gardasil was not studied in children with health problems or in combination with all other vaccines routinely given to American adolescents, such as Tdap and meningococcal vaccines.20
- To evaluate safety, rather than uniformly comparing Gardasil to an inert saline placebo, the vaccine was compared to its bioactive aluminum adjuvant component.21 Later, the majority of Gardasil 9 clinical trial results were bootstrapped by comparing the new Gardasil 9 vaccine to the old Gardasil vaccine.22
- After the original Gardasil vaccine was licensed for 11-12 year old girls and young women, thousands of adverse reaction reports were filed for: sudden collapse with unconsciousness within 24 hours, seizures, muscle pain and weakness, disabling fatigue, Guillain Barre Syndrome (GBS), facial paralysis brain inflammation, rheumatoid arthritis, lupus, blood clots, premature ovarian failure, optic neuritis, multiple sclerosis, strokes, heart and other serious health problems, including death.23 Similar reports have been filed for the Gardasil 9 vaccine,24 even though the recommended number of doses was reduced from three to two.
- Using the MedAlerts search engine, as of April 30, 2018, the federal Vaccine Adverse Events Reporting System (VAERS) contains more than 58,992 reports of HPV vaccine reactions, hospitalizations, injuries and deaths and, includes 430 related deaths, 794 hospitalizations, and 2,773 disabling conditions. Over 45 percent of the reported serious adverse events occurred in children and teens 12-17 years of age.
- As of June 29, 2018, 387 claims were filed with the federal Vaccine Injury Compensation Program (VICP) for injuries and deaths following HPV vaccination, which included 14 deaths and 376 serious injuries. Less than a third of claims received compensation.
Food & Drug Administration (FDA)
Centers for Disease Control (CDC)
Vaccine Reaction Symptoms & Ingredients
Our Ask 8, If You Vaccinate webpage contains vaccine reaction symptoms and more.
Search for Vaccine Reactions
NVIC hosts MedAlerts, a powerful VAERS database search engine. MedAlerts captures symptoms, reactions, vaccines, dates, geographic locations and more.
Reporting a Vaccine Reaction
Since 1982, the NVIC has operated a Vaccine Reaction Registry, which has served as a watchdog on VAERS. Reporting vaccine reactions to VAERS is required by law. If your doctor will not report a suspected vaccine reaction, you have the right to report it yourself.
IMPORTANT NOTE: NVIC encourages you to become fully informed about HPV and the HPV vaccine by reading all sections in the Table of Contents , which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.
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Learn More About HPV and HPV Vaccine
What Is HPV?
Human papillomaviruses are double-stranded DNA viruses found in the squamous epithelial cells on the surface of the skin and also the mucous membranes of the body.25 There are more than 200 known types of human papilloma viruses (HPVs) and most are not harmful.26 In the majority of cases, the human immune system clears HPV infections without symptoms or complications.27
More than 90 percent of those who become infected naturally clear the infection from the body within two years.28 Antibodies to the HPV type causing the infection remain in the body to help prevent future infections but the protection may not be life-long.29
Low Risk HPV Types - About 75 percent of HPVs have been associated with non-cancerous warts (papillomas) on the hands, chest, arms and feet, such as low-risk (wart-causing) HPV types 6 and 11.30 Low-risk HPV types associated with genital warts differ from high-risk HPV types that can be associated with development of cancer after years of chronic infection.31
High Risk HPV Types - About 40 HPV types have been found in the body’s mucosal membranes, such as the mucosal surfaces of the cervix, vagina, vulva, anus, penis, mouth and throat, including the most common high-risk HPV types 16 and 18. High-risk HPV types are associated with cancer of the cervix and five other genital and oral cancers affecting women and men if the HPV infection does not clear and becomes a chronic infection.32 High-risk HPV types currently include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73 and 82.33
The National Cancer Institute states that “Virtually all cervical cancers are caused by HPV infections, with just two HPV types, 16 and 18, responsible for about 70 percent of all cases.”34 HPV type 16 causes 95 percent of all anal cancers, 50 percent of all vulvar cancers, 65 percent of all vaginal cancers, 35 percent of all penile cancers and more than half of the oropharyngeal cancers in the United States.35
Is HPV Contagious?
Yes, HPV is contagious and more than 40 HPV types can be transmitted through sexual contact with an infected person. These 40 HPV types are found in the mucosal membranes of the body and transmitted through vaginal, oral or anal sex.36 Most of these HPV infections are asymptomatic and result in no clinical disease.37 Per the CDC, “More than 90% of new HPV infections, including those caused by high-risk HPV types, clear or become undetectable within 2 years, and clearance usually occurs in the first 6 months after infection.”38 In very rare cases, genital HPV types can be spread from mother to infant.39
Most HPV types - 75 percent - are skin (cutaneous) infections and are spread by skin-to-skin contact and are not sexually transmitted.40 Cutaneous HPV types can be found on the arms, hands, feet and legs41 and are associated with common warts.42
The CDC acknowledges that there are gaps in scientific knowledge about how, why and when HPVs are transmissible as noted below:
“HPV is presumably communicable during the acute infection and during persistent infection. This issue is difficult to study because of the inability to culture the virus. Communicability can presumed to be high because of the large number of new infections estimated to occur each year.”43
What is the history of HPV in America and other countries?
The first recorded research linking a sexually transmitted disease to cervical cancer dates back to an 1842 study by Rigoni-Stern, an Italian physician. After reviewing 80 years of female death certificates, he noted that cervical cancer deaths almost exclusively occurred in married or widowed women, and prostitutes.44 Early cervical cancer research focused on the Herpes Simplex II virus45 46 but this theory was disproven in 1984.47
In 1965, the first published HPV study characterized its DNA.48 Prior to 1965, papillomavirus studies focused on rabbit papillomavirus and its association to cancer.49 During the 1970’s, more than one type of HPV was recognized and by 1972, work was underway to evaluate an association between HPV and cervical cancer.50
In 1982, several studies associating HPV type 6 with genital warts, but not cervical cancer, were published.51 In 1983, HPV type 16 was identified in cervical cancer cells.52 A year later, HPV type 18 was linked to cervical cancer.53
HPV infections are endemic around the world and public health officials believe that it is the most common sexually transmitted infection in the U.S. with an estimated 14 million new infections occurring annually.54 Public health officials estimate that 79 million people in the U.S. are infected with HPV, a common infection in adolescents and young adults.55
Prevalence in U.S. Women – A 2007 study of female HPV prevalence reported that 26.8 percent of 14 to 59 year olds were infected but, among 20 to 24 year olds, 44.8 percent were infected.56 Low-risk HPV types 6 and 11 and high-risk HPV types 16 and 18 detected in 3.4 percent of females evaluated in the study. Researchers concluded that:
- Although HPV infection is common, studies suggest approximately 90 percent of infections clear within 2 years,
- HPV is common among U.S. females but the prevalence of the HPV types contained in the vaccine is relatively low, and
- High-risk HPV types are detected in 99 percent of cervical cancers and worldwide, approximately 70 percent of cervical cancers are due to HPV types 16 and 18.
In the early 1960’s, after Pap smear tests to screen for cancerous conditions became a routine part of women’s gynecological health care in the U.S., cases of HPV associated cervical cancer dropped by 75 percent.57 By 2006, the year Gardasil came to market, because of Pap test screening, new annual cervical cancer cases declined to about 9,700 and deaths to about 3,700 within a U.S. population of more than 300 million.58
Prevalence in U.S. Men - A 2006 review of 40 HPV prevalence studies found that, among U.S. males, prevalence rates ranged from 1.3 to 72.9 percent.59 The researchers concluded that:
- Data on the frequency of acquisition and the duration of HPV infection in men are limited,
- HPV prevalence rates in men vary widely and have been reported to be as high as what has been reported in women, and
- Screening for HPV infection in men is not routinely recommended because infection is very common, no FDA-approved screening test is available and HPV infection does not increase the risk of disease or cancer in men or their sex partners.
Can HPV Cause Injury and Death?
HPV infection usually causes no symptoms and most women and men clear the infection within one to two years.60 Antibodies to the HPV type that caused the infection remain in the body to help prevent future infections of that HPV type but the duration of protective immunity is unknown.61
Most, But Not All, HPV Infections Resolve Spontaneously - Sometimes an HPV infection does not clear from the body and thus, becomes a chronic infection. After many years of undetected chronic HPV infection, cervical and other genital or oral cancers can develop and cause disability or death. The CDC states that, “Although the incidence of infection is high, most infections resolve spontaneously. A small proportion of infected persons become persistently infected; persistent infection is the most important risk factor for the development of cervical cancer.”62
Persistent HPV infection associated with development of cervical cancer is clinically manifested in women by cervical intraepithelial neoplasia (CIN), which are referred to as “pre-cancerous” lesions. Low-grade CIN (CIN 1) may spontaneously resolve when infection clears from the body or it may progress to CIN 2 or CIN 3, which may lead to cervical cancer, if the pre-cancerous lesions are left undetected and untreated for years.63
The American Cancer Society states “Cervical cancer tends to occur in midlife and is most frequently diagnosed in women between the ages of 35 and 44. It rarely develops in women younger than 20. Many older women do not realize that the risk of developing cervical cancer is still present as they age. More than 15 percent of cases of cervical cancer are found in women over 65. However, these cancers rarely occur in women who have been getting regular tests to screen for cervical cancer before they were 65.”64
Women Need Pap Test Screening - Whether women have gotten HPV vaccinations or not, routine Pap test screening is recommended for all women to detect high grade CINs and receive prompt treatment in order to prevent cervical cancer from developing.65 66
Six HPV-Related Cancers - In addition to cervical cancer, there are five other cancers associated with chronic HPV infection: mouth and throat (oropharyngeal), vaginal, penile, anal and vulvar. In 2018, the American Cancer Society estimates that in the U.S. (population of over 325 million):
- About 13,240 cases of invasive cervical cancer will be diagnosed and result in 4,170 deaths.67
- About 51,540 cases of oral cavity or oropharyngeal cancer will be diagnosed and result in 10,030 deaths.68
- About 5,170 cases of vaginal cancer will be diagnosed and result in 1,330 deaths.69
- About 2,320 cases of penile cancer will be diagnosed and result in 380 deaths.70
- About 8,580 cases (5,620 in women and 2,960 in men) of anal cancer will be diagnosed and result in 1,160 deaths (680 in women and 480 in men).71
- About 6,190 cases vulva cancers will be diagnosed and result in 1,200 deaths.72
The CDC states, “About 10% of women with high-risk HPV on their cervix will develop long-lasting HPV infections that put them at risk for cervical cancer. Similarly, when high-risk HPV lingers and infects the cells of the vulva, vagina, penis, anus, or the oropharynx (back of the throat, including the base of the tongue and tonsils), it can cause cell changes called precancers. These may eventually develop into cancer if they're not found and removed in time and are much less common than cervical cancer. Less is known about how many people with HPV will develop cancer in these areas.”73
Low Number of HPV-Related Cancer Deaths – Each year, six HPV associated cancers cause about 18,000 deaths,74 less than three percent of the 595,000 annual U.S. cancer deaths.75.
Who is at highest risk for getting HPV?
Non-cutaneous HPVs are typically transmitted sexually. Over the course of their lifetime, more than 80 percent of women and 90 percent of men will become infected with at least one HPV type.76
Risk factors for acquiring HPV are directly related to sexual behavior of the individual and their partners. Epidemiologic studies are inconclusive as to whether other risk factors including genetics, age of sexual initiation, number of pregnancies, lack of circumcision of male partner, and tobacco use increase a person’s susceptibility to HPV infection.77
Who is at highest risk for suffering complications from HPV?
Risk factors for developing cancer, including HPV associated cancers, differ depending upon the cancer type, personal health, and lifestyle choices including those related to smoking, drinking and diet. That said, having one or more risk factors (or no risk factors) does not necessarily determine whether or not cancer will develop.
At highest risk of suffering HPV infection complications are the less than ten percent of women and men who do not naturally clear high-risk HPV infections and therefore, become chronically infected.78
According to the National Cancer Institute, factors that can increase the risk of developing cancer following chronic infection with high-risk HPV types include:79
- Having a weakened immune system
- Having many children (increases cervical cancer risk)
- Long-term oral contraceptive use (increases cervical cancer risk)
- Poor oral hygiene (increases oropharyngeal cancer risk)
- Chronic inflammation
The American Cancer Society80 lists the following risk factors for developing cervical cancer (after years of undiagnosed and untreated chronic infection with high risk HPV types):
- Chlamydia Infection
- Poor diet and obesity
- Long term oral contraceptive use
- Multiple full term pregnancies (three or more)
- Young age (under 17 years old) at the first full term pregnancy
- Poverty/lack of access to Pap tests
- Women whose mothers took the hormonal drug Diethystilbestrol (DES) during pregnancy (1940-1971)
- Family history of cervical cancer
Oral cavity and oropharyngeal cancers:81
- Tobacco use
- Alcohol use
- Heavy drinking and smoking
- HPV infection
- Gender (men at greater risk)
- Age (over age 55)
- UV Light
- Poor nutrition
- Weakened immune system
- Stem cell transplant recipients
- Genetic syndromes
- History of Lichen Planus disease
- HPV infection
- Other genital cancers (increased risk for women)
- HIV infection
- Multiple sexual partners
- Lowered immunity
- Race and gender
Vaginal and vulvar cancers:83
- HPV infection
- Cervical precancer or cervical cancer
- Weakened immune system
- Chronic vulvar itching or burning
- HPV infection
- Poor hygiene combined with lack of circumcision
- Smoking and other tobacco use
- UV light treatment of psoriasis
- Age (over age 55)
Can HPV be prevented and are there treatment options?
HPV infection prevention options focus on refraining from or limiting sexual activity in terms of numbers of partners and consistent use of condoms during all types of sexual activity including vaginal, anal and oral. There are no recommended treatments for HPV infection, which usually clears naturally, but there are options for treating genital warts and pre-cancerous lesions that develop after chronic infection.
Treatment Options: Anogenital warts and precancerous lesions are currently the only two conditions that warrant treatment.85
Treatment options for anogenital warts include use of anti-tumor medications, cryotherapy or surgical removal.86 Without treatment, anogenital warts may resolve spontaneously, remain the same, or may increase in number and size.87 HPV testing of genital warts is not recommended because the results will not affect treatment.88
Treatment options for precancerous cervical cells often identified subsequent to a Pap test, include the following options: cryotherapy (a process to freeze and destroy the cells), laser therapy (use of light beam to remove or kill the cells), loop electrosurgical excision procedure (LEEP) (electric current is passed through a wired loop and used as a blade to excise abnormal cells) and conization (cone-shaped tissue sample is cut away by either a laser, a knife, or by use of the LEEP procedure). Only cells determined to be cervical intraepithelial neoplasia, grade 2 (CIN-2) or higher require treatment due to their higher than average potential of progression to cancer if left untreated. Screening for all women who have had CIN-2 or higher lesions should continue for at least 20 years.89
The FDA has approved three vaccines: Cervarix, Gardasil, and Gardasil 9 for the prevention of HPV infection.90 Currently, only Gardasil 9, a 9-valent recombinant vaccine targeting HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, is available for use in the U.S.91
According to the CDC, in addition to recommending the HPV vaccine, prevention options include:92
- Abstaining from sexual activity (vaginal, anal, and oral).
- Using physical barriers, such as condoms, to reduce the risk of HPV transmission.
- Engaging in a monogamous relationship with an uninfected partner.
Stories & Photos of Gardasil Vaccine Reactions
What is HPV vaccine?
There are three FDA licensed HPV vaccines, however only one, Gardasil 9, approved in 2014 and manufactured by Merck, is currently available in the United States. Initially, HPV vaccines were given as a series of three shots over 6 months to protect against HPV infection and the health problems that ongoing HPV infection can cause. In 2016 the CDC recommended a two dose series with second dose administration between 6 to 12 months from the first dose.93 Below is information on the HPV vaccines licensed in the U.S.
- Gardasil 9: FDA approved Gardasil 9 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. According to Merck’s product insert, Gardasil 9 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
- Gardasil: FDA approved Gardasil for use in 2006. The safety of Gardasil was studied in clinical trials with more than 29,000 participants before it was licensed. According to Merck’s product insert, Gardasil protects against HPV types 6, 11, 16, and 18.
- Cervarix: FDA approved Cervarix for use in 2009. The safety of Cervarix was studied in clinical trials with more than 30,000 participants before it was licensed. According to GlaxoSmithKine’s product insert, Cervarix protects women and girls against HPV types 16 and 18.
Vaccines, like any medicine, can have side effects. Some people who get HPV vaccine have no side effects at all. Some people report having very mild side effects, like a sore arm from the shot. According to manufacturer product inserts,94 the most common side effects reported are usually mild and include:
- Pain, redness, or swelling in the arm where the shot was given
- Headache or feeling tired
- Muscle or joint pain
According to the Gardasil 9 product insert,95 brief fainting spells and related symptoms (such as jerking movements) can happen after any medical procedure, including vaccination. Sitting or lying down for about 15 minutes after a vaccination can help prevent fainting and injuries caused by falls.
On very rare occasions, severe (anaphylactic) allergic reactions can occur after vaccination. People with severe allergies to any component of a vaccine should not receive that vaccine.
Gardasil 996 is approved for use in girls and women ages 9 through 26 to prevent genital warts caused by Human Papillomavirus (HPV) types 6 and 11 and for the prevention of cervical, anal, vaginal, and vulvar cancers associated with HPV types 16, 18, 31, 33, 45, 52, and 58. Per the manufacturer’s product insert, Gardasil 9 also targets the following dysplastic and precancerous lesions associated with HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58:
- Cervical intraepithelial neoplasia (CIN) grade 1
- Cervical adenocarcinoma in situ (AIS) and cervical intraepithelial neoplasia (CIN) grade 2/3
- Anal intraepithelial neoplasia (AIN) grades 1, 2, and 3
- Vaginal intraepithelial neoplasia (VIN) grade 2 and 3
- Vulvar intraepithelial neoplasia (VIN) grade 2 and 3
Gardasil 9 is also approved for use in boys and men ages 9 through 26 to prevent genital warts caused by HPV types 6 and 11 and for the prevention of anal cancer associated with HPV types 16, 18, 31, 33, 45, 52, and 58. Per the manufacturer’s product insert, Gardasil 9 targets anal intraepithelial dysplasia (AIN) grades 1, 2, and 3 associated with HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.
According to Merck’s product insert, Gardasil 9, Human Papillomavirus 9-valent Vaccine, Recombinant, is a non-infectious recombinant 9-valent vaccine approved by the FDA for intramuscular administration. This vaccine is produced from the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The L1 proteins are formed by separate fermentations using recombinant Saccharomyces cerevisiae and self-assembled into virus-like particles. The fermentation process necessitates the growth of S. cerevisiae on a chemically-defined fermentation media which include carbohydrates, mineral salts, vitamins, and amino acids. The virus-like particles are freed from the yeast cells by cell disruption and purified by a series of physical and chemical methods. The purified virus-like particles are adsorbed on preformed Amorphous Aluminum Hydroxyphosphate Sulfate (AAHS), an aluminum containing adjuvant. The 9-valent Human Papillomavirus VLP vaccine is a sterile liquid suspension that is prepared by combining the adsorbed virus-like particles of each HPV type as well as additional amounts of the aluminum-containing adjuvant, AAHS, and the final purification buffer.
Merck’s Gardasil 9 product inserts states that each 0.5-mL dose contains approximately 30 mcg of HPV Type 6 L1 protein, 40 mcg of HPV Type 11 L1 protein, 60 mcg of HPV Type 16 L1 protein, 40 mcg of HPV Type 18 L1 protein, 20 mcg of HPV Type 31 L1 protein, 20 mcg of HPV Type 33 L1 protein, 20 mcg of HPV Type 45 L1 protein, 20 mcg of HPV Type 52 L1 protein, and 20 mcg of HPV Type 58 L1 protein.
Each 0.5-mL dose of the vaccine also contains approximately 500 mcg of aluminum (in the form of Amorphous Aluminum Hydroxyphosphate Sulfate), 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of polysorbate 80, 35 mcg of sodium borate, <7 mcg yeast protein, and water for injection.
The majority of pre-licensure clinical trials compared Gardasil 9 to Merck’s original Gardasil vaccine. In pre-licensure studies of the original Gardasil vaccine, Merck was permitted by the FDA to use Amorphous Aluminum Hydoxyphosphate Sulfate (AAHS), an aluminum adjuvant, in lieu of a saline placebo, as a control for nearly all of its trial participants.97 A reactive placebo, such as AAHS, has the ability to artificially increase the appearance of safety when used as a control in a clinical trial and neither the FDA nor Merck disclosed the amount of aluminum contained in the placebo. Both human and animal studies have shown that aluminum can enter the brain and that vaccine aluminum adjuvants can cause nerve cell death, as well as inflammation at the injection site leading to chronic muscle and joint pain and fatigue.98
What is the history of HPV vaccine use in America?
In the early 1980’s, studies confirmed the presence of HPV types 16 and 18 in cervical cancer cells,99 100 prompting research and development of a vaccine to prevent human papillomavirus (HPV). The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) first discussed HPV vaccine and issues related to assessing effectiveness at its licensure at the November 2001 meeting.101
Both Merck, the manufacturer of Gardasil102 and Gardasil 9,103 and GlaxoSmithKline, the manufacturer of Cervarix104 utilized new Virus-Like Particle (VLP) technology patented in 1994,105 to develop their HPV vaccines. VLPs contain particular proteins from the outside layer of the virus but lacks the genetic material to actually cause an infection.106 When injected, VLPs have the ability to produce an immune response due to the presence of foreign material.107
Merck’s original Gardasil vaccine was the first FDA approved HPV vaccine. It targeted HPV types 6, 11, 16, and 18. Gardasil was granted Fast Track approval by the FDA after only a six month review process.108 According to the FDA, Fast Track approval is a program designed to accelerate the review of medications targeting “serious conditions and fill an unmet medical need.”109 To meet the criteria of “unmet need”, a drug must demonstrate a greater benefit over the currently available treatment.
Prior to Gardasil vaccination, prevention of cervical cancer included regular Pap smears and additional treatment options including colposcopy and removal of any abnormal lesions by techniques such as Laser Electrosurgical Excision Procedure (LEEP). These treatment options continue to be the standard of care for screening and prevention of cervical cancer110 and are credited with decreasing the U.S. cervical cancer by 75 percent.111
Despite the availability of effective treatment options for the detection and prevention of cervical cancer, Gardasil was granted Fast Track status and an accelerated approval by the FDA.112 Accelerated approval is designed to allow drugs to be approved before they show any clinical benefit to the patient. Approval is based on findings associated with use of a “surrogate endpoint”, such as a physical marker, laboratory finding such as antibody levels or “other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit.”113 In other words, Gardasil did not have to demonstrate true effectiveness – prevention of cervical cancer – prior to being determined to be effective and granted approval and licensed by the FDA.
Invasive cervical cancer from an unresolved HPV infection can take decades114 to develop, and as a result, Merck’s pre-licensing studies of Gardasil, limited to five years,115 could not clinically confirm that its vaccine could actually prevent cervical cancer.116 The FDA also permitted Merck to use Amorphous Aluminum Hydroxyphosphate Sulfate (AAHS), an aluminum adjuvant, in lieu of a saline placebo, as a control in pre-licensure clinical trials of the original Gardasil.117 The safety of aluminum adjuvants in vaccines had previously been called into question118 119 120 prior to use in HPV vaccines and continued research on aluminum hydroxide in vaccines found it to be associated with long-term cognitive dysfunction121 122 in addition to chronic pain123 and fatigue.124 Yet, even with studies that linked aluminum to inflammation and chronic health issues, Merck was granted permission to use it as a control in pre-licensure safety studies.
On May 18, 2006, Merck presented data to the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which showed that Gardasil prevented cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3 and, as a result, the FDA approved the vaccine for use in girls and women ages 9 through 26.125 126
No clinical data to confirm Gardasil’s ability to prevent cervical cancer was available to VRBPAC. As a result, a “surrogate endpoint” – reduction in HPV related CIN 1, 2, and 3 related HPV types 16 and 18 – was used to infer whether the vaccine was likely to be effective. Using that metric, VRBPAC concluded that the vaccine was effective even though it had not been demonstrated to prevent cervical cancer.127 VRBPAC also voted to approve Gardasil for use in girls as young as 9 years of age even though very few girls between the ages of 9 and 15 were enrolled in pre-licensure studies.128
Concerns about the state of science at the point of licensure and prior to being reviewed by the CDC were summarized in a June 2006 NVIC press.129 Issues included clinical trial methods that involved use of bioreactive active placebos and known safety problems associated with injected aluminum, safety signals reported during pre-licensure clinical trials, inappropriate small sample sizes of the target population slated for vaccination, and an absence of proof of effectiveness.
Within weeks of Gardasil’s FDA approval, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend three doses of the vaccine for all 11 and 12 year old girls with a “catch up” schedule for females between the age of 13 and 26.130 Though Gardasil was recommended for use prior to the onset of sexual activity, females who were currently sexually active were also encouraged to take it without prescreening for current HPV infection, even though pre-licensing data noted that the vaccine had the potential to exacerbate a current HPV infection.131 The CDC’s press release on Gardasil’s recommendation for routine use failed to report the vaccine’s inability to treat pre-existing HPV infections, pre-cancerous lesions or cervical cancer.132
At the time of release, Gardasil was the most expensive vaccine in history, costing an average of $360 plus additional costs associated with medical office visits to complete the recommended three dose series.133 As a result, cost estimates to vaccinate all U.S. females between the age of 11 and 18 years of age were pegged at $2 billion.134
In 2005, one year prior to Gardasil’s FDA approval, over 1,500 Merck drug reps were redirected to focus on the Gardasil vaccine and Merck’s contributions to women’s health organizations and political campaigns increased substantially.135
Following FDA licensure and ACIP recommendation, Merck launched a highly aggressive marketing campaign targeting teenage girls by encouraging them to be “one less” victim of cervical cancer.136 In addition to the advertising campaigns directed at young women, Merck began extensive state level lobbying campaigns to make HPV vaccination mandatory for school entry. Merck’s efforts included lobbying state legislators, drafting legislation, seeking support from female legislators and physician trade organizations, and pushing to be the primary source of information on HPV vaccination. By 2007, 41 states and the District of Columbia had introduced HPV vaccine legislation including bills in 24 states that would make HPV vaccination a requirement for entry into 6th grade.137
In early 2007, HPV vaccine mandates and Merck’s legislative involvement was met with an enormous backlash from many consumer and family organizations that strongly opposed HPV vaccination mandates which were viewed as a violation of parental rights. Additionally, the Association of American Physicians and Surgeons and American Academy of Pediatrics expressed concerns related to safety, long-term effectiveness and reimbursement for such a costly vaccine.138
Early February 2007, Texas Governor Rick Perry signed an executive order mandating the HPV vaccine for all 6th grade girls 139 but this order was short-lived. Within three weeks of Perry’s decision to mandate the vaccine for school entry, the Texas House Committee on Public Health voted to rescind the executive order.140 The Senate followed suit and with both the Texas House and Senate’s overwhelming support of legislation to override the executive order, Perry opt to allow the override bill to become law.141 It was reported that Perry received $6,000 dollars in campaign contributions during his re-election campaign and one of the three Merck lobbyists in Texas previously worked as Perry’s chief of staff. Additionally, the mother-in-law of his chief of staff was also a state director for Women in Government,142 a national non-profit organization of female state legislators, received substantial contributions from Merck to direct attention on cervical cancer, HPV infections and Gardasil.143
By late February 2007, Merck’s aggressive state legislative lobbying efforts had backfired and it publicly announced the end of its campaign aimed at mandating the HPV vaccine for girls entering the 6th grade.144 Merck cited public accusations that profits, not public health, were motivating its campaigns as its reason for ceasing efforts to make Gardasil a mandatory vaccine.145 Only the District of Columbia and the Commonwealth of Virginia enacted legislation requiring HPV vaccination for all 6th grade girls. These laws, however, provided parents with the option of declining the vaccine for their daughters.146 147 In 2015, Rhode Island became the third jurisdiction to enact HPV vaccination legislation by requiring vaccination for both girls and boys entering the 7th grade.148
Reports of serious adverse events and deaths following vaccination with Gardasil began being reported to VAERS within weeks of FDA licensure and ACIP recommendation. In February 2007, NVIC released a press release149 and the first of three analyses of adverse reactions reported to VAERS 150 151 152 By May 2007, after being on the market for less than one year, VAERS had received 2,227 reports of serious adverse events following the administration of Gardasil. The early adverse reaction reports included seven deaths following receipt of Gardasil.
Additionally, an early NVIC analysis of VAERS data found a significantly greater risk of severe adverse events including Guillain-Barre Syndrome, respiratory and cardiac problems, central nervous system problems, convulsions, coordination and neuromuscular problems when Gardasil was administered along with another vaccine, Menectra, a meningococcal vaccine routinely administered to adolescents. No pre-licensure clinical trials evaluated safety when Gardasil was administered along with other vaccines targeted for use in teenagers.153
In June 2008, Judicial Watch, a conservative, non-partisan foundation, promoting transparency, accountability and integrity in government, published a 25 page special report154 detailing Gardasil’s approval process, marketing practices, side-effects, and safety concerns. At the time their report was published, 8,864 adverse reactions following Gardasil vaccination had been reported to VAERS, including 18 deaths. Reported side effects included blood clots, Guillain-Barre Syndrome (GBS), growth of warts, dizziness, nausea, convulsions, and headaches. The report also highlighted reports of miscarriages noting that Gardasil was not studied in pregnant women and evaluated as to whether it could cause fetal harm.155
Reports of serious reactions and deaths following HPV vaccination were also appearing in the media. These reports included seizures, paralysis, collapse, Guillain-Barre Syndrome as well as unexplained deaths.156 157 158 159 160 161 Yet, despite these concerns, the CDC continued to recommend the vaccine for all girls and young women, publicly denying any serious adverse events to be related to vaccination.
In July 2008, the CDC updated its Technical Instructions for the Medical Examination of Aliens in the United States and added the HPV vaccine as a requirement for all immigrant females between the age of 11 and 26, beginning on August 1st, 2008.162 163 While the update was intended to follow current guidelines requiring all immigrants to receive all appropriate CDC recommended vaccines, the update was criticized by many164 165 and on December 14, 2009, HPV vaccination was removed from the list of vaccines required for immigrants.166
To address the growing concerns raised by the public and medical professionals about Gardasil’s safety, in August 2009, the FDA and CDC posted a document on the FDA’s website that summarized the approval process and an overview of the safety monitoring process and findings to date.167
Additionally, federal agency staff published the same information in a 2009 Journal of the American Medical Association (JAMA) article summarizing the Gardasil’s safety.168 After reviewing 12,424 VAERS reports the authors noted that 772 (6 percent of reports) were for serious events including 32 deaths. The article provides the reporting rates for syncope, local site reactions, dizziness, nausea, headache, hypersensitivity reactions, urticarial, venous thromboembolic events, autoimmune disorders and Guillain-Barre Syndrome, anaphylaxis, pancreatitis, transverse myelitis, motor neuron disease and death. The authors concluded that the rates of these events, except for syncope and venous thromboembolic events, were no different than background rates. The methods used and conclusions drawn for the analysis were criticized in a published letter to JAMA’s editor, which concluded that the reassurances of Gardasil’s safety were unsupported.169
Merck continued to push for expanded use of its Gardasil vaccine and on October 16, 2009, the FDA approved Gardasil for use in boys and young men ages nine to twenty-six for the prevention of genital warts associated with HPV types 6 and 11, even though the vaccine had been studied in only about 3,000 males.170 Again, nearly all pre-licensing clinical trials failed to use an inert true placebo as a control and instead, used the novel bioactive aluminum adjuvant (Amorphous Aluminum Hydoxyphosphate Sulfate).171 While ACIP declined to recommend Gardasil for routine use in males, it did state that Gardasil could be administered to boys and men, ages 9 to 26 for the purpose of reducing the risk of developing genital warts associated with HPV types 6 and 11.172 Two years later, in October 2011, the ACIP voted to recommend routine vaccination with 3 doses of Gardasil for all boys ages 11-12 years with a catch up schedule for males ages 13 through 21 years.173
Merck also submitted a request to the FDA for Gardasil to be approved in women between the ages of 27 and 45, but the FDA declined this request August 2010 due to a lack of data supporting substantial benefit for this population.174 175
In October 2009 Cervarix,176 a bivalent recombinant vaccine manufactured by GlaxoSmithKline targeting HPV types 16 and 18, received FDA approval for use in girls ages 10 through 25 years of age for the prevention of CIN grades 1, 2 and higher, adenocarcinoma in situ, and cervical cancer.177 Cervarix contained a novel adjuvant named AS04 which is made of a lipid (MPL) and aluminum and had not previously been used in vaccines licensed in the U.S. In pre-clinical trials, the safety of Cervarix was assessed by comparing it to a licensed vaccine that is assumed to be safe - Hepatitis A which contained up to 5000 mcg of Aluminum Hydroxide (AL(0H)3).178 Within days of FDA approval, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend 3 doses of Cervarix for routine administration to girls ages 11 or 12, with a catch up schedule for females ages 13 through 26.179 However, by October of 2016, citing low demand for its product, GlaxoSmithKline announced that Cervarix would no longer be marketed in the United States.180
In 2011, at the request of SaneVax, a non-profit organization promoting “only Safe, Affordable, Necessary & Effective vaccines and vaccination practices through education and information,”181 Sin Hang Lee, a Board Certified Pathologist, tested 13 different vials of Gardasil vaccine and discovered that each one contained Human Papillomavirus (HPV) DNA.182 In August 2011, SaneVax notified the FDA of these findings and requested an investigation and information about the effect of HPV DNA presence on vaccine safety.183 In response, on October 21, 2011, the FDA released a statement acknowledging the presence of HPV DNA fragments in the vaccine and stating that they regarded this as normal due to the vaccine’s manufacturing process rather than a vaccine contamination problem.184 No additional studies were recommended to determine whether the presence of HPV DNA in the vaccine posed any risks to vaccine recipients.
Severe adverse reactions following HPV vaccination continued to be reported in the United States and abroad.185 186 187 In June of 2013, the Japanese government withdrew their support of HPV vaccination, citing safety concerns related to the high number of serious adverse reactions reported following vaccination.188 Three years later, in July of 2016, Japanese victims of HPV vaccination launched a class action lawsuit against the Japanese government, Merck, the maker of Gardasil, and GlaxoSmithKline, the maker of Cervarix, for damages related to the numerous health problems suffered post-vaccination.189
American journalist Katie Couric, profiled HPV vaccination during a December 2013 segment of her TV talk show, Katie. The program discussed the benefits and risks of vaccination and interviewed two mothers who reported sudden serious health issues that followed their daughters HPV vaccinations.190 Couric’s program resulted in an onslaught of attacks from numerous media sources accusing her of promoting junk science and fear mongering.191 192 193 194 195 196 197 198 After enduring several days of negative media stories, Couric published a blog commentary199 in the Huffington Post stating that the show should have focused more on the vaccine’s safety and efficacy, and less on the “serious adverse events that have been reported in very rare cases following the vaccine.”200
While mainstream media in the U.S. has effectively silenced nearly all discussion questioning the safety of HPV vaccination, reports in other countries have continued to surface.
In March 2015, one of Denmark’s national television stations aired a documentary focusing on the serious side effects reported following HPV vaccination and profiling the stories of three young women who developed chronic health problems following HPV vaccination.201 At the request of Danish scientists and clinicians, the European Medicines Agency (EMA), the agency responsible for safety monitoring and scientific evaluation of drugs and vaccines in Europe, reviewed two commonly reported side effects of HPV vaccination, postural orthostatic tachycardia syndrome (POTS) and complex regional pain syndrome (CRPS), and determined that no link existed between these symptoms and HPV vaccination.202 However, several scientists and doctors objected to the report, expressing concerns over conflicts of interest and use of inappropriate methods that relied on previously published data.203
Reports of serious side effects following HPV vaccination in Denmark have continued where parents are expressing concern over the vaccine’s safety.204 Ireland’s TV3 television station aired a similar documentary December 2015 profiling several girls who developed debilitating health problems following HPV vaccination.205 In 2017, Sacrificial Virgins,206 a United Kingdom documentary was shown at several independent film festivals which discussed the lack of evidence proving that HPV vaccination and prevents cervical cancer, reports of debilitating side effects and death, and HPV vaccine litigation in Japan, Spain, and Columbia. Despite numerous reports from around the world of serious side effects and death following HPV vaccination, in most cases, government health agencies continue to actively promote HPV vaccine use and contend that the vaccine is effective and is not linked to any serious side effects or death.207 208 209
Over time, it became clear that Merck’s original Gardasil vaccine formulation was inadequate in addressing all the HPV types of concern. As a result, Merck increased the number of types of HPV from four to nine and on December 10, 2014, its 9-valent recombinant vaccine (Gardasil 9) received FDA approval for use in females ages 9 through 26 years of age, for the prevention of genital warts associated with HPV Types 6 and 11 and for the prevention of anal, cervical, vaginal, and vulvar cancers associated with HPV Types 16, 18, 31, 33, 45, 52, and 58.210 The FDA also approved Gardasil 9 for use in males ages 9 through 15 for the prevention of genital warts associated with HPV Types 6 and 11 and for the prevention of anal cancer associated with HPV Types 16, 18, 31, 33, 45, 52, and 58.211 In addition to doubling the amount of HPV protein antigen contained in the original Gardasil, Merck’s Gardasil 9 increased the amount of bioactive aluminum adjuvant to from 225 mcg to 500mcg.212
As previously noted for Gardasil, pre-licensure studies of Gardasil 9 did not use true placebos as controls and instead, tended to compare Gardasil 9 to Gardasil.213 In February 2015, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to recommend 3 doses of Gardasil 9 to be administered to all males and females ages 11-12, with a catch up dosing for females between the age of 13 and 26, males between the age of 13 and 21, and select high-risk males up to the age of 26 years of age. Gardasil 9 was recommended by the ACIP in males between the age of 13 and 21 even though the FDA had yet to approval its use in males over 15 years of age.214 One year later, the FDA approved Gardasil 9 for use in males ages 16 to 26 in December 2015.215
Two years after Gardasil 9 was licensed by the FDA, in December 2016, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to decrease the recommended 3-dose schedule to a 2-dose schedule for HPV vaccination in females and males between the ages of 9 and 14 where the second dose was to be administered six to twelve months following the initial dose. The 3-dose vaccine schedule continued to be recommended for individuals receiving the first HPV dose after the age 15. The ACIP stated that the dosing changes were based on evidence that the immune response in persons between the age of 9 and 14 after two doses of HPV vaccine was significant enough to produce adequate long lasting antibodies against HPV types present within the vaccine.216 At the same time, Gardasil 9 became the only available HPV vaccine on the market in the U.S. The CDC recommended using “any HPV vaccine at the recommended dosing schedule” to complete the vaccination schedule for vaccines that were no longer available even though no studies existed to support the use of “a mixed regimen of HPV vaccines”.217
Despite Merck’s 2016 marketing campaign,218 which appears to shame parents for declining Gardasil for their children, HPV vaccination uptake rates remain low. A 2018 published report219 on HPV vaccination rates in adolescents completed by the insurance company Blue Cross Blue Shield found that, in 2016, only 34 percent of teenagers had received their first dose of HPV vaccine by the age of 13. This study also found that only 9 percent of adolescents had completed the series prior to the age of 13. An additional survey of over 700 parents whose children had not received the HPV vaccine reported that over half of the parents were not planning to have their child receive HPV vaccination and 60 percent of these parents cited vaccine safety concerns as the reason they decided to decline HPV vaccination for their child.220
In June 2018 the FDA granted Merck a priority review of its application to expand Gardasil 9 use in both males and females 27 to 45 years of age.221 Previously, the FDA reviewed data for women ages 27 to 45, in August 2010 and concluded that the vaccine showed no significant benefit to this population. A decision is expected in October of 2018.
For females over 21 years of age, HPV vaccination does not replace the need for routine Pap smear testing to detect abnormal cells that can cause cervical cancer especially considering that cervical cancer can be caused by HPV types not included in the vaccine.222 The effectiveness of HPV vaccination is still unknown and according to the CDC, “it may take decades to see population-level impact” from this vaccine.223
Who should not get HPV vaccine?
According to the CDC anyone who has ever had a life-threatening allergic reaction to a previous dose of HPV vaccine should not get another dose. Anyone with a severe allergy to any part of the vaccine should not receive the vaccine. The CDC also advises that anyone with any severe allergies, including a severe allergy to yeast, should notify their doctor prior to vaccination. HPV vaccine is not recommended for pregnant women. People who are moderately or severely ill at the time the vaccine is scheduled should wait until they recover before getting HPV vaccine.224
While the CDC states that HPV vaccine may be administered to women who are breastfeeding,225 the manufacturer’s product insert reports that there are insufficient studies available to assess the effects of the vaccine on milk production/excretion or on the breastfed infant.226 Gardasil 9, the only HPV vaccine currently available in the United States, is approved for males and females between the ages of 9 and 26. Persons younger than 9 or older than 26 should not receive this vaccine.227
Information about contraindications (reasons why a person should not get a vaccine) to HPV vaccine are contained in the manufacturer’s product information package insert that accompanies vials of vaccine provided to doctors and other medical personnel administering the vaccine, and can also be found on the FDA’s website.
How effective is HPV vaccine?
As of August 2018, there are no studies that confirm HPV vaccine has reduced the incidence of HPV associated cancers. According to CDC data, HPV associated increased to cancers 41,000 cases between 2010 to 2014228 from 26,000 cases between 2004 and 2008.229 During CDC’s Advisory Committee on Immunization Practices (ACIP) February 2018, it was reported that “it may take decades to see population-level impact due to the length of time between the initial HPV infection and the development of cancer.”230
HPV vaccines cannot treat existing HPV infections and does not protect against HPV types not covered by the vaccine. In fact, 21 percent of HPV associated cancers involve HPV types not included in Gardasil 9.231 HPV vaccine does not replace the need for routinely recommended cervical or anal cancer screenings.232 If vaccinated women opt to skip routine cervical cancer screening, cervical cancer rates are expected to increase.233 Cervical cancer has been reported in women who have received HPV vaccine.234
Long-term effectiveness studies of Gardasil found the vaccine to be between 88.4 and 94.4 percent effective against HPV Type 6; 89.1 and 95.5 percent effective against HPV Type 11; 96.8 to 99.1 percent effective against HPV Type 16; and 60 to 64.1 percent effective against HPV Type 18 after nine years.235 A 2017 Merck funded study of five year Gardasil 9 antibody levels and concluded that the vaccine was 97.4 percent effective against the HPV Types covered by the vaccine.236 Research studies indicate that, unless HPV vaccination produces high antibody titers for at least 15 years, vaccination alone will not prevent cervical cancer.237
Can HPV vaccine cause injury and death?
The most commonly reported side effects of HPV vaccination include pain, swelling, and redness at the injection site, nausea, headache, fever, fatigue, and muscle or joint pain. Fainting – referred to as a syncopal episode - following HPV vaccination has been frequently reported and as a result, it is recommended that individuals receiving the vaccine remain sitting or lying down to prevent syncope and any potential injuries that may result from a fall.238 However, more severe reactions have also been reported in HPV vaccine clinical trials and to the federal Vaccine Adverse Events Reporting System (VAERS). See Human Papillomavirus (HPV) Quick Facts for 2018 reports of HPV vaccine reactions, hospitalizations, injuries and deaths made to VAERS.
Some of the adverse events reported by the manufacturers during pre-licensing clinical trials included:
Gardasil - injection site pain, swelling, redness and bruising, fever, headache, nausea, dizziness, syncope, sometimes in conjunction with seizure-like activity, anaphylaxis, diarrhea, vomiting, cough, upper respiratory tract infection, nasal congestion, insomnia, malaise, oropharyngeal pain, nasopharyngitis, upper abdominal pain, gastroenteritis, appendicitis, pelvic inflammatory disease, urinary tract infection, pneumonia, pulmonary embolism, pyelonephritis, bronchospasm, and death.239
Cervarix - injection site pain, redness, bruising and swelling, syncope, fatigue, headache, gastrointestinal symptoms, rash, fever, arthralgia, myalgia, urticarial, urinary tract infection, back pain, dysmenorrhea, nasopharyngitis, influenza, vaginal infection, pharyngitis, chlamydia infection, arthritis, rheumatoid arthritis, Celiac disease, diabetes mellitus, erythema nodosum, inflammatory bowel disease, hyperthyroidism, hypothyroidism, multiple sclerosis, transverse myelitis, systemic lupus erythematosus, thrombocytopenia, vasculitis, optic neuritis, vitiligo, and death.240
Gardasil 9 - injection site pain, swelling, redness, and bruising, syncope, fever, headache, nausea, dizziness, fatigue, diarrhea, upper respiratory tract infection, upper abdominal pain, oropharyngeal pain, myalgia, asthmatic crisis, anaphylaxis, and death.241
Gardasil 9 reported post marketing adverse events include: pulmonary embolus, idiopathic thrombocytopenic purpura, lymphadenopathy, autoimmune hemolytic anemia, pancreatitis, asthenia, chills, fatigue, malaise, bronchospasm, urticarial, anaphylaxis, acute disseminated encephalomyelitis, dizziness, transverse myelitis, Guillain-Barré syndrome, headache, motor neuron disease, paralysis, seizures, syncope (including syncope associated with other seizure-like activity and tonic-clonic movements) sometimes resulting in injury from falling, deep vein thrombosis, cellulitis, myalgia, arthralgia, and death.
In 2007, NVIC reviewed adverse events reported to the Vaccine Adverse Events Reporting System (VAERS), and noted a statistically significant increased risk of Guillain-Barre Syndrome(GBS) and other serious adverse events when Gardasil was administered with other vaccines, especially the meningococcal vaccine, Menactra. The analysis noted a 1,130 percent increase in GBS, a 674 percent increase in injuries from falls after loss of consciousness, a 234 percent increase in coordination and neuromuscular problems, a 118 percent increase in cardiac problems, a 114 percent increase in respiratory problems and a 30.1 percent increase in convulsions and central nervous system problems when Gardasil was administered with Menactra.242
During the past decade, there have been numerous studies and reports linking HPV vaccination to chronic illnesses in children and young adults. These include anaphylaxis,243 lupus,244 245 erythema multiforme,246 acute disseminated encephalomyelitis,247 248 249 transverse myelitis,250 amyotrophic lateral sclerosis (ALS),251 central nervous system demyelination,252 253 multiple sclerosis,254 including pediatric multiple sclerosis,255 Guillain-Barre Syndrome,256 257 pancreatitis,258 259 inflammatory bowel syndrome,260 brachial plexus neuritis,261 brachial neuritis,262 optic neuritis,263 neuromyelitis optica,264 opsoclonus myoclonus,265 evanescent white dot syndrome,266 267 acute cerebellar ataxia,268 autoimmune hepatitis,269 autoimmune neuromyotonia,270 vasculitis,271 thrombocytopenic purpura,272 immune thrombocytopenic purpura,273 Postural Orthostatic Tachycardia Syndrome (POTS),274 275 276 Complex Regional Pain Syndrome (CRPS),277 Chronic Fatigue Syndrome (CFS),278 and peripheral sympathetic nerve dysfunction.279 A published questionnaire280 of HPV vaccination recipients focusing on a combination of chronic illness including POTS, CRPS, and fibromyalgia found that 93 percent of individuals reporting symptoms related to these conditions were still incapacitated and unable to work or attend school four years after vaccination. Additionally, several studies have linked HPV vaccination to primary ovarian failure resulting in impaired fertility281 282 283 284. A 2018 study found lower pregnancy rates in women who had received HPV vaccination.285
Adverse events following HPV vaccination have also been linked to a relatively new medical condition termed Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA).286 In 2011, Dr. Yehuda Shoenfeld, the founder and head of the Zabludowicz Center for Autoimmune Diseases in Israel, published a paper associating four medical conditions - Gulf War syndrome (GWS), macrophagic myofasciitis syndrome (MMF) (a syndrome previously related to the use of aluminum adjuvants), siliconosis (a condition related to silicone breast implants) and post-vaccination phenomena (chronic illness following vaccination) to a previous adjuvant exposure.
Dr. Shoenfeld noted that patients suffering from these conditions presented with very similar clinical symptoms. Since then, published studies have linked the aluminum adjuvant found in the HPV vaccine several to chronic health conditions including postural tachycardia syndrome (POTS),287 primary ovarian failure (POF), 288 chronic epipharyngitis,289 pseudo-neurological syndrome,290 and severe somatoform and dysautonomic syndromes.291 An epidemiological study of data collected from the federal Vaccine Adverse Events Reporting System (VAERS) estimated that 3.6 out of 100,000 doses of HPV vaccination resulted in symptoms that were consistent with a diagnosis of ASIA.292
An animal study on the effects of HPV vaccination found that both the HPV antigens and the aluminum adjuvant appear to have the ability of trigger autoimmune reactions and neuroinflammation in female mice, leading to changes in behavior patterns.293
Studies linking HPV vaccination to sudden death in previously healthy women have also been published. A 2012 published case study of two deaths following HPV vaccination concluded that the HPV-16L1 antigens present in HPV vaccines have the potential to cause fatal autoimmune vasculopathies.294 Also in 2012, Sin Hang Lee, a research scientist and board certified pathologist, published a case study involving the sudden and unexplained death of a young women six months after completing a three dose series of Gardasil. Dr. Lee found in the blood and spleen HPV-16 gene DNA that were similar to HPV-16 gene DNA fragments in Gardasil. The HPV-16 LI gene DNA was bound to the same aluminum adjuvant found in the vaccine, which protected it from degradation. It continues to be unknown whether or not these HPV DNA fragments played a role in the girl’s death.
A 2017 article published in Drug Safety reviewed safety concerns associated with HPV vaccination.295 Data reported to reported to adverse reaction reporting systems from several countries were analyzed and found to contain relatively high numbers of reports for headache, dizziness, fatigue, and syncope associated with prolonged hospitalization or debilitation. While some of the reports listed Postural Orthostatic Tachycardia Syndrome (POTS), Complex Regional Pain Syndrome (CRPS) or Chronic Fatigue Syndrome (CFS) as a diagnosis, the vast majority of the reports lacked any diagnosis. This study also found significantly higher number of events involving a combination of dizziness and headache with either syncope or fatigue following HPV vaccination compared to adverse reactions of other vaccines. It was also noted that these combinations of symptoms were first reported in countries that were the earliest to approve and recommend HPV vaccination and that reported symptoms persisted globally.
Due to these findings, others have questioned whether current drug and vaccine safety monitoring tools have the ability to adequately detect and respond to signals indicating that a serious problem may exist with a product currently on the market.296 Additionally, a 2018 study noted that only about half of the available clinical trials involving HPV vaccines had been completed before the vaccines were approved by both the Federal Drug Administration (FDA) and the European Medicines Agency (EMA).297 The study also noted that drug manufacturers only published the results of about two-thirds of the HPV clinical trials, leaving the study’s authors to question whether drug manufacturers were selectively choosing which clinical data to publish.
In December 2017, Slate Magazine published a cover story on the pre-licensure clinical trials of the Gardasil vaccine. 298 This investigational report determined that Merck’s pre-licensure safety studies “used a convoluted method that made objective evaluation and reporting of potential side effects impossible during all but a few weeks of its years long trial.”299 The article noted that Merck’s clinical trial investigators were permitted to use personal judgment when reporting medical problems as an adverse event, essentially allowing study investigators to decide what symptoms might possibly be related to vaccination. Study investigators were also allowed to list new health issues following vaccination as medical history, not adverse events, and limited safety follow up to 14 days following each of the three doses of Gardasil vaccination. Slate’s investigation located several women involved in Gardasil’s pre-licensure trials who reported chronic illness post-vaccination to study investigators, yet their symptoms were never reported by Merck.
In April 2018, the Indian Journal of Medical Ethics published a report suggesting that Sweden’s increase in cervical cancer rates might be associated with HPV vaccination. The study’s author, concerned that he may be targeted for questioning a vaccine’s safety or efficacy, chose to publish under an assumed name without contacting the journal in advance. Initially, the journal chose to allow the article to be published despite the deception after determining that the author had both the necessary credentials and faced a credible threat of harm, stating “the issues raised by it are important and discussion on it is in the public interest.”300 However, two weeks later, after receiving “valuable advice from the journal’s editorial board and others”, the article was retracted.301 The journal, however, stated that they “hope that the hypothesis of possible harm of vaccinating women previously exposed to HPV is carefully explored in future studies.”302 Data from Gardasil’s pre-licensure clinical trials had previously demonstrated a higher incidence of cervical intraepithelial neoplasia (CIN) grade 2 and 3 in women previously infected with the particular strain targeted by the vaccine.303
According to federal VAERS data, 430 deaths following the HPV vaccination have been reported following HPV vaccination.304 However, the number of HPV vaccine related injuries and deaths reported to VAERS is assumed to underreported as explained below.
Even though the National Childhood Vaccine Injury Act of 1986 legally required pediatricians and other vaccine providers to report serious health problems following vaccination to the federal vaccine adverse event reporting system (VAERS), many doctors and other health care providers giving vaccines to children and adults fail to report vaccine-related health problem to VAERS. The evidence suggests that only one to 10 percent of serious health problems that occur after use of prescription drugs or vaccines in the U.S. are ever reported to federal health officials who are responsible for regulating the safety of drugs and vaccines and issue national vaccine policy recommendations.305 306 307 308 309
As of July 1, 2018, 387 claims have been filed to the federal Vaccine Injury Compensation Program (VICP) for 14 deaths and 373 injuries that occurred after HPV vaccination. To date, the U.S. Court of Claims has compensated 128 of the 387 children and adults who filed claims for HPV vaccine injuries.310
For example, an HPV vaccine injury claim was filed and awarded by the VICP for Christina Tarsell. Christina was a 21-year-old college student majoring in studio arts at Bard College when she received a series of three Gardasil shots. A talented athlete, artist and honor roll student, she died suddenly and without explanation shortly after the third shot in June 2008. Ten years later, in 2018, the government conceded the case and awarded compensation to her mother for Christina’s vaccine-related death.311
Who is at highest risk for complications from HPV vaccine?
The Institute of Medicine has acknowledged that there is individual susceptibility to vaccine reactions for genetic, biological and environmental reasons but that vaccine providers cannot accurately predict prior to a vaccine’s administration who will suffer complications, injury or death from vaccination.312 However, a person who has previously had a serious reaction to a vaccination or is acutely or chronically ill should become informed about all potential risks associated with vaccination and discuss any concerns with a trusted health care professional before receiving HPV vaccine or any other vaccine.
A 2013 study examining an association between systemic lupus erythematosus (SLE) or SLE-like disease and HPV vaccination noted that individuals with a personal or family history of auto-immunity or those who had previously reacted to HPV vaccination had a higher risk of developing an auto-immune disorder post vaccination.313 A 2017 case report published in Clinical Pediatrics reported a case of neurocardiogenic syncope and postural orthostatic tachycardia syndrome in a previously healthy 11-year-old female with a family history of autoimmune disease post Gardasil vaccination.314
Currently, a history of a severe allergy to a vaccine component, including yeast, history of a life threatening allergic reaction to a previous HPV shot, and pregnancy are the only CDC approved official contraindications (medical reasons for not getting vaccinated) to receiving HPV vaccines.315 However, the CDC also states that HPV vaccination should be postponed if a person is “moderately or severely ill.”316
What questions should I ask my doctor about the HPV vaccine?
NVIC’s If You Vaccinate, Ask 8! webpage and downloadable brochure suggests asking eight questions before you make a vaccination decision for yourself, or for your child. If you review these questions before your appointment, you will be better prepared to ask your doctor questions. Also make sure that the nurse or doctor gives you the relevant Vaccine Information Statement (VIS) for the vaccine or vaccines you are considering well ahead of time to allow you to review it before you or your child gets vaccinated. Copies of VIS for each vaccine are also available on the CDC's website and there is a link to the VIS for HPV vaccine on NVIC's “Quick Facts” at the top of this page.
Due to the brevity of the VIS, it is also a good idea to read the vaccine manufacturer product insert that can be obtained from NVIC’s HPV Quick Facts, doctor or public health clinic to get additional information. Federal law requires drug companies marketing vaccines to include certain kinds of vaccine benefit, risk and use information in product information inserts that may not be available in other published information, like the VIS.
Other questions that may be useful to discuss with your doctor before getting the HPV vaccine are:
- If other vaccines in addition to HPV vaccine are scheduled for my child at this office visit, am I allowed to modify the schedule so fewer vaccines are given at once?
- What are the possible side effects that may occur following vaccination?
- What should I do if my child has a high fever or appears very ill after vaccination?
- What other kinds of reaction symptoms should I call to report after HPV vaccination?
- Are there other options for preventing HPV infection?
It also is important to be able to recognize a vaccine reaction and seek immediate medical attention if the reaction appears serious, as well as know how to make a vaccine reaction report to federal health officials at the Vaccine Adverse Reporting System (VAERS). NVIC’s Report Vaccine Reactions—It’s the Law webpage can help you file a vaccine reaction report yourself to VAERS if your doctor fails or refuses to make a report.
NVIC Press Releases, Statements, Reports and Video Collection on Gardasil Vaccine
NVIC HPV Video Playlist
View the collection of video resources within the player below for more information on HPV and HPV vaccine.
To view the entire video collection, click the hamburger menu in the upper left corner of the video player above. This will expand a full list of videos. You may also open the video player in full screen mode for optimal display.
NVIC Statements & Commentaries
Commentaries & Statements
- Gardasil Vaccine, Katie Couric & Cyber-Lynching. Fisher, B.L. Jan. 29, 2014.
- Gardasil & Swine Flu Vaccine: Inconvenient Truths. Fisher, B.L. Aug. 24, 2009.
- Preventing Gardasil Injuries & Deaths. Fisher, B.L. Jul. 14, 2009.
- Gardasil Death & Brain Damage: A National Tragedy. Fisher, B.L. Feb. 9, 2009.
- Letter: NVIC HPV Vaccine Safety Analysis Part III to Advisory Committee on Immunization Practices (ACIP) of Centers for Disease Control. Aug. 14, 2007
- Analysis of Gardasil Vaccine Adverse Events Part III. Fisher, B.L., Debold, V., Downey, C. - Aug. 15, 2007
- NVIC Report/Analysis of Gardasil Vaccine Adverse Events Part II. Debold, V., Fisher, B.L. Feb. 21, 2007.
- NVIC Analysis of Gardasil Vaccine Adverse Events Part I. Debold, V., Fisher, B.L. Feb. 1, 2007.
- Survey of GARDASIL Costs in Private Pediatricians Offices. Feb. 1, 2007.
Additional Bibliography of References
Select Broadcast Media Reports on Gardasil Vaccine
- Dec. 9, 2013. CBS-TV - The Doctors. HPV Vaccine Controversy.
- Aug. 19, 2009. “Gardasil Researcher Speaks Out,” a report by Sharyl Attkisson, CBS-TV.
- Feb. 6, 2009. Gardasil Vaccine Draws Concerns, a report by Sharyl Attkisson, CBS Evening News.
- Nov. 11, 2008. “One Mother’s Story & Bigger Questions About the U.S. Vaccine Safety System,” an investigate report by Jane Miller, WBAL-TV 11 (Baltimore).
- July 7, 2008. “Gardasil Concerns,” a report by Nancy Yamada, WUSA-TV (Washington, DC).
- February 13, 2007. “Should HPV Vaccine Be Mandatory?” Meredith Viera moderated debate with Nancy Snyderman, MD; Barbara Loe Fisher, NVIC President; Jessica Farrar, TX legislator. “Today Show,” NBC-TV.
Selected Print Media Reports
- Cluskey P. Sharp drop in number of Dutch teenage girls getting HPV vaccination. The Irish Times. Jun. 27, 2018.
- Sagonowsky E. Merck CEO: Gardasil plus pipeline equals big things ahead for vaccines. FiercePharma. Jun. 12, 2018
- Llamas M. Florida Mom Says HPV Vaccine Ruined Daughter’s Life. Drugwatch. May 15, 2018.
- Pulla, P. Understanding the HPV vaccine’s risk. The Hindu. Feb. 5, 2018.
- Joelving F. What the Gardasil Testing May Have Missed. Slate. Dec. 17, 2017.
- Cullen P. Almost 650 girls needed medical intervention after HPV vaccine. The Irish Times. Sep. 12, 2017.
- Guevara C. Class Action Lawsuit Against HPV Vaccine Filed in Colombia. Medscape. Aug. 7, 2017.
- Aoki, M. Suit opens in Tokyo court over cervical cancer vaccine side effects. The Japan Times Feb. 13, 2017
- Chustecka Z. Class Action Lawsuit Against HPV Vaccine Filed in Japan. Medscape. Jul. 27, 2016.
- Chustecka Z. Complaint Filed Over EMA's Handling of HPV Vaccine Safety Issues. Medscape. Jul. 5, 2016
- Chustecka Z. Case Reports of 'Syndrome' Appearing After HPV Vaccination. Medscape. Sep. 18, 2015
- Gallagher P. Thousands Of Teenage Girls Report Feeling Seriously Ill After Routine School Cancer Vaccination. The Independent. May 31, 2015.
- Dennis B. Five pressing health priorities in 2014. Washington Post. Dec. 28, 2013.
- Sanofi sued in France over Gardasil vaccine. Reuters. Nov. 24, 2013.
- Merck Press Release - Business Wire. Merck’s Investigational 9-Valent HPV Vaccine, V503, Prevented 97 Percent of Cervical, Vaginal and Vulvar Pre-cancers Caused by Five Additional HPV types, in Phase III Study. Nov. 4, 2013.
- Baklinski T. Japan Withdraws Support of Controversial HPV Vaccine Over Safety Concerns. Lifesite News. Oct. 16, 2013.
- Mulcahy, N. Japan Withdraws HPV Vaccine Recommendation for Girls. Medscape. Jun. 25, 2013.
- Castillo M. Side effect fears stop parents from getting HPV vaccine for daughters. CBS News. Mar 18, 2013.
- Gonthier V. Family Sues After Teen Dies Following HPV Vaccination. Toronto Sun. Jan. 31, 2012.
- Green G. Gardasil: Krystal’s Story. Women Hurt by Medicine. May 14, 2010.
- People’s Daily Online. HPV vaccine comes under spotlight in S. Korea. Xinhuanet. Jun. 8, 2010.
- New Report Explores Gardasil Deaths. Jun. 14, 2010.
- Medical News Today. Cost-Effectiveness of HPV Vaccination in The Netherlands. July 4, 2009.
- Scoop Independent News (NZ). Vaccine Roll-Out Is Wrong Without Honest Advice. Feb. 28, 2009.
- Hart, B. “Gardasil Vaccine for boys?” Seattle Post Intelligencer . Jan. 16, 2009.
- “FDA Again Says No to Expanded Gardasil Use”. Wall Street Journal. Jan. 9, 2009.
- “New Gardasil cervical cancer vaccination requirements for immigrants stirs controversy”. NY Daily News. Oct. 24, 2008.
- “Merck Aims Gardasil to Women Least Likely to Benefit”. Bloomberg News. Oct.17, 2008.
- “Study Questions Cost Effectiveness of Gardasil Cervical Cancer Vaccine”. Wall Street Journal. Aug. 21, 2008.
- “Drug Makers Push Leads to Cancer Vaccine’s Rise. New York Times. Aug. 19, 2008.
- Edelman S. Fed’s Warning Shot. New York Post. Jul. 6, 2008.
- “My Girl Died as ‘Guinea Pig’ for Gardasil” New York Post. Jul. 20, 2008.
- “Is HPV Vaccine To Blame for Teen’s Paralysis?” US News & World Report. Jul. 2, 2008.
- “Judicial Watch Uncovers New FDA Records Detailing Ten New Deaths & 140 “Serious” Adverse Events Related to Gardasil.” Judicial Watch. June 30, 2008.
- “Anti-Vaccine Activists vs. Gardasil”. Time Magazine. Jun. 19, 2008.
- December 6, 2007: Fox News — “28 Women Miscarry After Receiving HPV Vaccine Gardasil: FDA Says No Reason to Re-examine Approval.”
- “Merck Reaffirms 2007 Profit Outlook”. MSNBC. Dec. 4, 2007.
- “Vaccines Give Merck Booster Shot.” TheStreet.com. Nov. 2, 2007.
- “Merck Vaccine Should Be Required, Global, Experts Say” Bloomberg News. Sep. 21, 2007.
- “HPV Vaccine Flags Need for More Pap Tests.” AlterNet.org. Sep. 7, 2007.
- “Oral-Sex Cancer Link Suggests Boys Need Merck Vaccine”. Bloomberg News. Aug. 27, 2007.
- Family Awaits News on Daughter’s Illness. The Record-Courier. May 23, 2007.
- Dan Walters Column. Sacramento Bee. May 11, 2007.
- UCSF Doctors Warn on Wide Use of Cervical Cancer Vaccine. San Francisco Chronicle. May 10, 2007.
- “Merck posts 12% profit rise, affirms 2007 forecast”. Market Watch. Apr. 19, 2007.
- “VA set to Mandate Gardasil”. Boston Globe. Mar. 3, 2007.
- Merck Stops Campaign to Mandate Gardasil Vaccine Use. Bloomberg News. Feb. 20, 2007.
- Drugmaker Assists In Pushing for Mandate For HPV. Washington Post. Feb. 11, 2007.
- Merck Gets First U.S. Cancer-Shot Mandate, From Texas. Bloomberg News. Feb. 2, 2007.
- Letter to the Editor from Barbara Loe Fisher, “Risk, Racism and the HPV Vaccine”. Washington Post. Feb. 1, 2007.
- “Force Is Not the Only Way to administer a Vaccine” by Courtland Milloy. Washington Post. Jan. 24, 2007.
- D.C. Bill Would Mandate Vaccine. Washington Post. Jan. 10, 2007.
- “A New Vaccine for Girls, But Should It Be Compulsory?” by Roni Rabin. New York Times. Jul. 18, 2006.
Selected Medical Literature Articles
- Shiller JT, Lowy DR. Papillomavirus-Like Particle Vaccines. J Natl Cancer Inst. Monogr 2000; 28: 50-54.
- Baylor NW, Egan W, Richman P. Aluminum salts in vaccines – US perspective. Vaccine 2002; May 31 20Supple 3: 518-523.
- Burg EM. Human Papillomavirus and Cervical Cancer. Clin Microbiol Rev 2003; 16(1): 1-17.
- Haug CJ. Human Papillomavirus Vaccine: Reason for Caution. NEJM 2008; 359: 861-862.
- Slade BA, Leidel L, Vellozzi C, Woo EJ et al. Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine. JAMA 2009; 302(7): 750-757.
- Sutton I, Lahoria R et al. CNS Demyelination and Quadrivalent Vaccination. Mult Scler 2009; 15: 116-119.
- Rothman SM, Rothman DJ. Marketing HPV Vaccine: Implications for Adolescent Health and Medical Professionalism. JAMA 2009; 302(7): 781-786.
- Haug C. The Risks and Benefits of HPV Vaccination. JAMA 2009; 302(7): 795-796.
- Alvarex-Sonia MJ, Hernandez-Gonzalez A et al. Demyelinating Disease and Vaccination of the Human Papillomavirus. Rev Neurol 2011; 52(8): 472-476.
- Souayah N, Michas-Martin PA. Guillain Barre syndrome after Gardasil vaccination: data from Vaccine Adverse Events Reporting System 2006-2009. Vaccine 2011; 29(5) 886-889
- Klein NP, Hansen J et al. Safety of Quadrivalent Human Papillomavirus Vaccine Administered Routinely to Females. JAMA Pediatrics 2012; 166(12): 1140-1148.
- Soldevilla HF, Brones SFR, Navarra SV. Systemic lupus erythematosus following HPV immunization. Lupus 2012; 21: 158-161.
- Van Bogaert LJ. Are the currently existing anti-human papillomavirus vaccines appropriate for the developing world? AMHSR 2013; 3(3): 306-312.
- Pons-Salort M, Tiebault ACM et al. HPV genotype replacement: too early to tell. The Lancet Infectious Diseases 2013; 13(12): 1012.
- Arnheim-Dahlstrom L, Pasternak B et al. Autoimmune, neurologic, and venous thromboembolic adverse events after immunization of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ 2013; 347
- Mariani L, Venuti A. HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future. Journal of Translational Medicine 2010; 8:105.
- Colafranceso S Perricone C et al. Human Papilloma Virus Vaccine and Primary Ovarian Failure: Another Facet of Autoimmune/Inflammatory Syndrome Induced by Adjuvants. American Journal of Reproductive Immunology 2013.
- Binagwaho A, Wagner CM et al. Achieving a high coverage in Rwanda’s national human papillomavirus programme. Bulletin of the World Health Organization 2012; 90: 623-28.
- Batson A, Meheus F, Brooke St. Chapter 26: Innovative financing mechanisms to accelerate the introduction of HPV vaccines in developing countries. Vaccine 2006.
- Gupta S., Kerkar R A., et al. Is human papillomavirus vaccination likely to be a useful strategy in India? South Asian J Cancer. 2013 Oct-Dec; 2(4): 193–197.
- Tomljenovic, L., Colafrancesco, S., et al. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants” Case Report and Literature Review. J Investig Med High Impact Case Rep. 2014 Jan-Mar; 2(1): 2324709614527812.
- Little, D.T., Ward, H.R., Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination: A Case Series Seen in General Practice. J Investig Med High Impact Case Rep. 2014 Oct 28;2(4):2324709614556129
- Palmieri B, Piddighe D et al. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res 2017; 65(1): 106-116.
- Chandler RE, Juhlin K et al. Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase. Drug Safety 2017; 40_ 81-90.
- Chandler, R.E. Safety Concerns with HPV Vaccines Continue to Linger: Are Current Vaccine Pharmacovigilance Practices Sufficient? Drug Saf. 2017; 40(12): 1167–1170.
- Cervantes LJ, Doan AH. Discrepancies in the evaluation of the safety of the human papillomavirus vaccine. Mem Inst Oswaldo Cruz 2018; 113(8).
- Jørgensen L., Gøtzsche P.C., et al Index of the human papillomavirus (HPV) vaccine industry clinical study programmes and non-industry funded studies: a necessary basis to address reporting bias in a systematic review. Syst Rev. 2018; 7: 8.
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« Return to Vaccines & Diseases Table of Contents
1 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Background. 6th Edition, 2013.
2 American Cancer Society. HPV Vaccines – What is HPV? Jun. 5, 2018
3 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute. Feb. 19, 2015.
4 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Disease Description. 6th Edition, 2013.
5 Ho GYF, Studentsov YY. et al. Natural History of Human Papillomavirus Type 16 Virus-Like Particle Antibodies in Young Women. Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):110-6.
6 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Disease Description. 6th Edition, 2013.
7 American Cancer Society. What women should know about cervical cancer. Apr. 2016
8 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute. Feb. 19, 2015.
9 Safaeian M, Soloman D. Cervical Cancer Prevention - Cervical Screening: Science in Evolution. Obstet Gynecol Clin North Am. 2007 Dec; 34(4): 739–ix.
10 National Institutes of Health (NIH). Human Papillomavirus (HPV) Vaccines - Do women who have been vaccinated still need to be screened for cervical cancer? May 16, 2018
11 CDC. ACIP Meeting Presentation – Trends in HPV-associated cancers in the United States. Dr. Elizabeth VanDyne, CDC/NCIRD. Feb. 12, 2018.
12 CDC. United States Cancer Statistics: Data Visualizations – Leading Cancer Cases and Deaths, Male and Female, 2015.
13 U.S. Census Bureau. Annual Estimates of the Resident Population: April 1, 2010 to July 1, 2015. May, 2016.
14 CDC. United States Cancer Statistics: Data Visualizations – Leading Cancer Cases and Deaths, Male and Female, 2015.
15 Meites E., Kempe, A., Marowitz, LE. Use of 2-Dose Schedule for Human Papillomavirus Vaccination – Updates Recommendations of the Advisory Committee on Immunization Practices. MMWR. 2016;65:1405-1408. Dec. 16, 2016.
16 FDA Approved Products - Gardasil 9. Indications. Feb. 26, 2018.
17 FDA Gardasil 9 – Product insert. Feb. 9, 2018
18 FDA Gardasil – Product insert. Apr. 24, 2015
19 FDA Cervarix – Product insert. Apr. 25, 2016
20 NVIC Preventing Gardasil Vaccine Injuries & Deaths. Jul. 14, 2009
21 FDA Gardasil – Product insert. Apr. 24, 2015
22 FDA Gardasil 9 – Product insert. Feb. 9, 2018
23 MedAlerts Gardasil VAERS Reports. May 14, 2018
24 MedAlerts Gardasil 9 VAERS Reports. May 14, 2018
25 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
26 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Background. 6th Edition, 2013.
27 Ault KA, Epidemiology and Natural History of Human Papillomavirus Infections in the Female Genital Tract. Infect Dis Obstet Gynecol. 2006;2006(Suppl.):40470.
28 Cubie HA, Diseases associated with Human Papillomavirus infection. Virology. 2013 Oct;445(1-2):21-34.
29 Trottier H, Ferreira S. et al HPV infection and re-infection in adult women: the role of sexual activity and natural immunity. Cancer Res. 2010 Nov 1; 70(21): 8569–8577.
30 American Cancer Society. HPV Vaccines – What is HPV? Jun. 5, 2018
31 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute. Feb. 19, 2015.
32 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
33 Schmitt M, Dondog B. et al. Abundance of Multiple High-Risk Human Papillomavirus (HPV) Infections Found in Cervical Cells Analyzed by Use of an Ultrasensitive HPV Genotyping Assay. J. Clin. Microbiol. Jan. 2010 vol. 48 no. 1 143-149
34 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute. Feb. 19, 2015.
36 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute. Feb. 19, 2015.
37 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Background. 6th Edition, 2013.
39 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
40 Mercola. Know the Different HPV Types and How They Can Affect Your Health. No date.
42 American Academy of Dermatology Association. Warts: Overview. No Date.
43 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
44 Zur Hausen H. Papillomaviruses in the causation of human cancers – a brief historical account. Virology. Feb. 20, 2009, 384 (2): 260-265.
45 Rawls WE, Tomkins WA, et al. Herpesvirus type 2: association with carcinoma of the cervix. Science. 1968 Sep 20;161(3847):1255-6.
46 Josey WE, Nahmias AJ, Naib ZM. Genital infection with type 2 herpesvirus hominis. AJOG. July 1, 1968, 101(5): 718-729.
47 Zur Hausen H. Papillomaviruses in the causation of human cancers – a brief historical account. Virology. Feb. 20, 2009, 384 (2): 260-265.
49 Rous P, Beard JW. THE PROGRESSION TO CARCINOMA OF VIRUS-INDUCED RABBIT PAPILLOMAS (SHOPE)*. J Exp Med. 1935 Sep 30; 62(4): 523–548.
50 Zur Hausen H. Papillomaviruses in the causation of human cancers – a brief historical account. Virology. Feb. 20, 2009, 384 (2): 260-265.
52 Durst M, Gissmann L. et al. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983 Jun; 80(12): 3812–3815.
53 Boshart M, Gissmann L. et al. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May; 3(5): 1151–1157.
54 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
56 Dunne EF, Unger ER. et al. Prevalence of HPV Infection Among Females in the United States. JAMA 2007; 297(8): 876-878.
57 Safaeian M, Soloman D. Cervical Cancer Prevention - Cervical Screening: Science in Evolution. Obstet Gynecol Clin North Am. 2007 Dec; 34(4): 739–ix.
58 Business Wire Merck Launches National Advertising Campaign for GARDASIL®,
Merck's New Cervical Cancer Vaccine. Nov. 13, 2006.
59 Dunne EF, Nielson CM. et al. Prevalence of HPV Infection Among Men: A Systematic Review of the Literature. J Infect Dis 2006; 194(8): 1044-1057.
60 CDC. Surveillance Manual – Chapter 5: Human Papillomavirus (HPV) - Background. 6th Edition, 2013.
62 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
64 American Cancer Society. Key Statistics for Cervical Cancer. Jan. 4, 2018.
65 American Cancer Society. HPV Vaccines – What is HPV? Jun. 5, 2018.
66 Henderson L, Clements A. et al. ‘A false sense of security?’ Understanding the role of the HPV vaccine on future cervical screening behaviors a quantitative study of UK parents and girls of vaccination age. J Med Screen 2011; 8(1): 41-45.
67 American Cancer Society. Key Statistics for Cervical Cancer. Jan. 4, 2018.
68 American Cancer Society. Key Statistics for Oral Cavity and Oropharyngeal Cancers Mar. 9, 2018.
69 American Cancer Society. Key Statistics for Vaginal Cancer Mar. 19, 2018.
70 American Cancer Society. Key Statistics for Penile Cancer Jun. 25, 2018..
71 American Cancer Society. Key Statistics for Anal Cancer Jan. 4, 2018.
72 American Cancer Society. Key Statistics for Vulvar Cancer Jan 16, 2018.
73 CDC. Basic Information About HPV-Associated Cancers. Sept. 5, 2013.
74 See References #47 – #52.
75 CDC. Cancer Data (U.S.): Mortality. May 3, 2017.
76 Chesson HW, Dunne EF. et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis. 2014 Nov; 41(11):660-4.
77 CDC. Human Papillomavirus - Epidemiology. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
78 CDC. Basic Information About HPV-Associated Cancers. Sept. 5, 2013
79 National Institutes of Health (NIH). HPV and Cancer. National Cancer Institute Feb. 19, 2015.
80 American Cancer Society. What are the risk factors for cervical cancer? Nov 1, 2017..
81 American Cancer Society. What are the risk factors for oral cavity and orophayngeal cancers? Mar. 9, 2018.
82 American Cancer Society. What are the risk factors for anal cancer? Nov. 13, 2017.
83 CDC. Gynecologic Cancers Vaginal and Vulvar Cancers Risk Factors. Mar. 12, 2014.
84 American Cancer Society. What are the Risk Factors for Penile Cancer? Jun. 25, 2018
85 CDC 2015 Sexually Transmitted Diseases: Human Papillomavirus (HPV) Infection. Jan 25, 2017.
86 CDC 2015 Sexually Transmitted Diseases: Anogenital Warts. Jun. 4, 2015
87 CDC Human Papillomavirus (HPV) Treatment and Care. Oct. 31, 2017
88 CDC 2015 Sexually Transmitted Diseases: Anogenital Warts. Jun. 4, 2015
89 National Institutes of Health (NIH) Pap and HPV Testing. National Cancer Institute Sep. 9, 2014.
90 FDA Vaccines Licensed for Use in the United States. Mar 29, 2018.
91 CDC Vaccine Information Statements (VISs) What’s New with VISs. Mar 21, 2018
92 CDC. Human Papillomavirus. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). 13th ed. 2015.
93 Meites E., Kempe, A., Marowitz, LE. Use of 2-Dose Schedule for Human Papillomavirus Vaccination – Updates Recommendations of the Advisory Committee on Immunization Practices. MMWR. 2016;65:1405-1408. Dec. 16, 2016.
94 FDA. Human Papillomavirus Vaccine – Approved Products. Feb. 2, 2018.
95 FDA Gardasil 9 – Product insert. Feb. 9, 2018
96 FDA Gardasil 9 – Product insert. Feb. 9, 2018
97 FDA Gardasil – Product insert. Apr. 24, 2015
98 NVIC Merck’s Gardasil Vaccine Not Proven Safe for Little Girls. Press Release. Jun. 27, 2006
99 Durst M, Gissmann L. et al. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983 Jun; 80(12): 3812–3815.
100 Boshart M, Gissmann L. et al. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May; 3(5): 1151–1157.
101FDA. Meeting transcript - Vaccines and Related Biological Products Advisory Committee (VRBPAC). Nov. 28-29, 2001.
102 FDA Gardasil – Product insert. Apr. 24, 2015
103 FDA Gardasil 9 – Product insert. Feb. 9, 2018
104 FDA Cervarix – Product insert. Apr. 26, 2016
105 Grimes JL. HPV Vaccine Development: A case study of prevention and politics. IUMBM Journals. Nov. 3. 2006
106 National Institutes of Health (NIH) NCI Dictionary of Cancer Terms - virus-like particle. National Cancer Institute. No Date.
107 Grimes JL. HPV Vaccine Development: A case study of prevention and politics. IUMBM Journals. Nov. 3. 2006
108 Tomljenovic L, Shaw CA. Too fast or not too fast: the FDA's approval of Merck's HPV vaccine Gardasil. J Law Med Ethics. 2012 Fall;40(3):673-81
109 FDA Fast Track Jan. 4. 2018
110 National Institutes of Health (NIH) Understanding Cervical Changes: Next Steps After an Abnormal Screening Test. National Cancer Institute. Feb. 21, 2017.
111 Safaeian M, Soloman D. Cervical Cancer Prevention - Cervical Screening: Science in Evolution. Obstet Gynecol Clin North Am. 2007 Dec; 34(4): 739–ix.
112 Tomljenovic L, Shaw CA. Too fast or not too fast: the FDA's approval of Merck's HPV vaccine Gardasil. J Law Med Ethics. 2012 Fall;40(3):673-81
113 FDA Accelerated Approval. Jan 4, 2018
114 Pubmed Health. Cervical Cancer: overview. Informed Health Online. Dec. 14, 2017
115 Villa LL, Costa RLR. et al High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4; 95(11): 1459–1466.
116 Tomljenovic L, Shaw CA. Too fast or not too fast: the FDA's approval of Merck's HPV vaccine Gardasil. J Law Med Ethics. 2012 Fall;40(3):673-81
117 FDA Gardasil – Product insert. Apr. 24, 2015
118 Gherardi RK, Coquet M. et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain. 2001 Sep;124(Pt 9):1821-31.
119 Gherardi RK, Authier FJ, Aluminum inclusion macrophagic myofasciitis: a recently identified condition. Immunol Allergy Clin North Am. 2003 Nov;23(4):699-712.
120 Shingde M, Hughes J. et al. Macrophagic myofasciitis associated with vaccine-derived aluminium. Med J Aust. 2005 Aug 1;183(3):145-6.
121 Couette M, Boisse MF. et al. Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction. J Inorg Biochem. 2009 Nov;103(11):1571-8
122 Passeri E, Villa C. et al. Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF). J Inorg Biochem. 2011 Nov;105(11):1457-63.
123 Gherardi RK, Authier FJ. Macrophagic myofasciitis: characterization and pathophysiology. Lupus. 2012 Feb;21(2):184-9
124 Exley C, Swarbrick L. et al. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009 Feb;72(2):135-9
125 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006
126 FDA Center for Biologics Evaluation and Research. Summary Minutes. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006
127 FDA Gardasil – Product insert. Apr. 24, 2015
128 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006
129 NVIC. Merck’s Gardasil Vaccine Not Proven Safe for Little Girls. June 27, 2006
130 CDC Advisory Committee on Immunization Practices. June 29-30, 2006. Atlanta Georgia. Record of the Proceedings. Jun. 29-30, 2006
131 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006
132 CDC CDC’s Advisory Committee Recommends Human Papillomavirus Virus Vaccination. Press Release. Jun.29, 2006
133 Kotz D. 5 Things to Consider Before Getting the HPV Vaccine. U.S. News and World Report. Sep. 2, 2008
134 Harris G. Panel Unanimously Recommends Cervical Cancer Vaccine for Girls 11 and Up. New York Times. Jun 30, 2006
135 Editorial Flogging Gardasil. Nature Biotechnology 25, page 261 (2007). Mar. 1, 2007
137 Mello MM, Abiola S, Colgrove J. Pharmaceutical Companies’ Role in State Vaccination Policymaking: The Case of Human Papillomavirus Vaccination. Am J Public Health. 2012 May; 102(5): 893–898.
138 Editorial Flogging Gardasil. Nature Biotechnology 25, page 261 (2007). Mar. 1, 2007
139 Associated Press Texas Governor Orders STD Vaccine for all Girls – Decision comes after maker of cervical cancer shot doubled lobbying efforts. NBC News Feb. 3, 2007
140 Elliot J. House panel votes to block HPV order - Panel votes to block HPV vaccine requirement. Houston Chronicle. Feb. 22, 2007.
141 Elliot J. Perry won’t veto bill blocking his HPV order. Houston Chronicle. May 8, 2007.
142 Associated Press Texas Governor Orders STD Vaccine for all Girls – Decision comes after maker of cervical cancer shot doubled lobbying efforts. NBC News Feb. 3, 2007.
143 Mello MM, Abiola S, Colgrove J. Pharmaceutical Companies’ Role in State Vaccination Policymaking: The Case of Human Papillomavirus Vaccination. Am J Public Health. 2012 May; 102(5): 893–898.
144 Pollack A, Saul S. Merck agrees to stop lobbying for mandatory use of cervical cancer vaccine – Business – International Herald Tribune. New York Times. Feb. 21, 2007.
145 Gardner A. Merck to Stop Pushing to Require Shots. Washington Post. Feb 21, 2007
146 Yang E. DC Requiring Girls to Get HPV Vaccine This Fall -Parents can opt out of otherwise mandatory vaccine. NBC Washington. Aug. 11, 2009.
147 Craig T. Kaine Says He'll Sign Bill Making Shots Mandatory. Washington Post. Mar. 3, 2007.
148 Borg L. Rhode Island to mandate HPV vaccine for all 7th graders. Providence Journal. Jul. 28, 2015.
149 NVIC. HPV Vaccine Mandates Risky and Expensive. Vaccine Safety Group Finds Serious Reactions, High Costs. HPV. Feb. 1, 2007.
150 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 1, Adverse Reactions, Concerns and Implications. Feb. 1, 2007.
151 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 2. Feb. 21, 2007.
152 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 3. Aug. 15, 2007.
153 NVIC Analysis Shows Greater Risk of GBS Reports When HPV Vaccine Is Given with Meningococcal and Other Vaccines. Aug 15, 2007.
154 Judicial Watch. A Judicial Watch Special Report – Examining the FDA’s HPV Vaccine Records. Jun. 30, 2008.
156 Edelman S. FED’S WARNING SHOT. New York Post. Jul. 6, 2008.
157 Kotz D. Is HPV Vaccine to Blame for a Teen's Paralysis? U.S. News and World Health Report. Jul. 2, 2008.
158 Ashton J. HPV Vaccine Risk. CBS Early Show. Aug. 19, 2008.
159 Attkisson S. Is HPV Vaccine Safe? CBS Evening News. Jul. 7, 2008.
160 Edelman S. My Girl Died as a ‘Guinea Pig” for Gardasil. New York Post. Jul. 20, 2008.
161 Attkisson S. Gardasil Vaccine Draws Concern. CBS Evening News. Feb. 7, 2009.
162 Jordan M. Gardasil Requirement for Immigrants Stirs Backlash. The Wall Street Journal. Oct. 1, 2008.
163 Black R. New Gardasil cervical cancer vaccination requirement for immigrants stirs controversy. New York Daily News. Oct. 24, 2008.
164 Hachey KJ, Allen RH. et al. Requiring human papillomavirus vaccine for immigrant women. Obstet Gynecol. 2009 Nov;114(5):1135-9.
165 James SD. Girl Rejects Gardasil, Loses Path to Citizenship. ABC News. Sep. 11, 2009.
166 Associated Press HPV vaccine no longer required for green cards. NBC News. Nov 16, 2009.
167 FDA Gardasil Vaccine Safety, Information from FDA and CDC on the Safety of Gardasil Vaccine. Aug. 20, 2009.
168 Slade B, Leidel L, Vellozzi C et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. Aug. 19, 2009.
169 Debold V, Hurwitz E. Adverse Events and Quadrivalent Human Papillomavirus Recombinant Vaccine. JAMA. 2009;302(24):2657-2658. doi:10.1001/jama.2009.1880.
170 FDA Oct. 16, 2009 Approval Letter – Gardasil. Oct. 16, 2009
171 FDA Clinical Review Gardasil, October 16, 2009. Sep. 29, 2009
172 CDC. FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR. May 28, 2010 / 59(20);630-632.
173 CDC. Recommendations on the Use of Quadrivalent Human Papillomavirus Vaccine in Males — Advisory Committee on Immunization Practices (ACIP), 2011. MMWR. December 23, 2011 / 60(50);1705-1708.
174 FDA. Summary Basis for Regulatory Action - Gardasil, August 25, 2010. Aug. 25, 2010.
175 Gever J. FDA Rejects Gardasil for Older Women. MEDPAGE TODAY, Apr. 7, 2011.
176 FDA Cervarix – Product insert. Apr. 25, 2016.
177 FDA October 16, 2009 Approval Letter – Cervarix. Oct. 16, 2009.
178 FDA Cervarix – Product insert. Apr. 25, 2016.
179 CDC. FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR. May 28, 2010 / 59(20);626-629.
180 Mulcahy N. GSK’s HPV Vaccine, Cervarix, No Longer Available in US. Medscape. Oct. 24, 2016.
181 SaneVax About Us. Accessed Sep.14, 2018.
182 Botha LC. SANE Vax Discovers Potential Bio-hazard Contaminant in Merck’s Gardasil™ HPV 4 Vaccine. SANE Vax Inc. Sep. 5, 2011
183 Erickson, N. SANE Vax to FDA: Recombinant HPV DNA found in multiple samples of Gardasil. SANE Vax Inc. Sep. 2, 2011
184 FDA. FDA Information on Gardasil – Presence of DNA Fragments Expected, No Safety Risk, Oct. 21, 2011
185 Laino C. 2 ALS Cases May Be Linked to Gardasil Vaccine. WebMD. Oct. 16, 2009
186 Gonthier V. Family sues after teen dies following HPV vaccination. Toronto Sun. Jan. 31, 2012
187 Green G. Krystal’s Story. Women Hurt by Medicine. May 14, 2010
188 Mulcahy N. Japan Withdraws HPV Vaccine Recommendation for Girls. Medscape. Jun. 25, 2013
189 Chustecka Z. Class Action Lawsuit Against HPV Vaccine Filed in Japan. Medscape. Jul. 27, 2016
190 NVIC. Gardasil Vaccine, Katie Couric and Cyber-Lynching. Jan. 14, 2014
191 Hiltzik, M. Katie Couric Puts the Anti-Vaccination Movement Into the Mainstream. LA Times. Dec. 4, 2013.
192 Sifferlin A. Is Katie Couric the Next Jenny McCarthy? Time Magazine Dec. 4, 2013
193 Blake, M. Katie Couric Under Fire for Allegedly Slanted Report on HPV Vaccine. LA Times Dec. 5, 2012.
194 Marcotte A. Katie Hands Over Her Show to Anti-Vaccine Alarmists. Slate Dec. 4, 2013.
195 Monookin S. Katie Couric Promotes Dangerous Fear Mongering with Show on the HPV Vaccine. PLOS Blogs Dec. 3, 2013.
196 Herper M. Four Ways Katie Couric Stacked the Deck Against Gardasil. Forbes Dec. 4, 2013.
197 Willingham E. Katie Couric Promotes Anticancer Vaccine Alarmism. Forbes Dec. 4, 2013.
198 McDonough K. Katie Couric Gets Called Out for Promoting Bogus Science on HPV Vaccine.Salon.com Dec. 4, 2013.
199 Couric K. Furthering the Conversation on the HPV Vaccine. Huffington Post. Dec. 10, 2013
201 Erickson N. HPV Vaccines: A Danish Documentary. SaneVax, Inc. Apr. 28, 2015
202 European Medicines Agency HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS. Jan. 12, 2016
203 Chustecka Z. Complaint Filed Over EMA's Handling of HPV Vaccine Safety Issues. Medscape. Jul. 5, 2016
204 Gadd S. Side-effects stories affecting HPV vaccination numbers. CPHPOST Online. May 10, 2017
205 Maher D. Lives of 130 teenage girls 'ruined by cancer vaccine', families claim. Irish Mirror. Dec. 14, 2015
206 Shenton J, Reiss A. Sacrificial Virgins. Meditel Productions and Yellow Entertainment. 2017
207 CDC Frequently Asked Questions about HPV Vaccine Safety. Apr. 11, 2018
208 European Medicines Agency Gardasil Sep.18, 2017
209 European Medicines Agency Cervarix Jan. 3, 2018
210 FDA. Gardasil 9 – Product insert. Feb. 9, 2018
211 FDA. December 10, 2014 Approval Letter -GARDASIL 9. Dec. 10, 2014
212 FDA. Summary Basis for Regulatory Action – GARDASIL 9 Dec. 9, 2014
213 FDA. Gardasil 9 – Product insert. Feb. 9, 2018
214 CDC. Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommendations of the Advisory Committee on Immunization Practices. MMWR. Mar. 27, 2015 / 64(11);300-304.
215 FDA December 14, 2015 Approval Letter – GARDASIL 9. Dec. 14, 2015.
216 CDC Use of a 2-Dose Schedule for Human Papillomavirus Vaccination — Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR. Dec. 16, 2016 / 65(49);1405–1408
217 FDA Gardasil 9 – Product insert. Feb. 9, 2018
218 Bulik BS. Merck holds parents accountable in new Gardasil ad campaign. Fierce Pharma. Jun. 28, 2016
219 BCBS Adolescent vaccination rates in America. The Health Of America. Feb. 13, 2018.
220 PR Newswire Blue Cross Blue Shield Association Study Shows Low Uptake of HPV Vaccine Compared to Other Adolescent Immunizations. Feb. 13, 2018
221 Merck FDA Grants Priority Review to Merck’s Supplemental Biologics License Application (sBLA) for GARDASIL®9 in Women and Men Ages 27 to 45 for the Prevention of Certain HPV-Related Cancers and Diseases. Press Release. Jun. 13, 2018.
222 National Institutes of Health (NIH) Pap and HPV Testing. National Cancer Institute. Sep. 9, 2014
223 ACIP Meeting Presentation – Trends in HPV-associated cancers in the United States. Dr. Elizabeth VanDyne, CDC/NCIRD. Feb. 12, 2018.
224 CDC. HPV (Human Papillomavirus) VIS. Dec. 2, 2016
226 FDA. Gardasil 9 – Product insert. Feb. 9, 2018
228 CDC. United States Cancer Statistics – Data Brief – Cancers associated with human papillovavirus, United States-2010-2014. No. 1. Dec. 2017.
229 CDC. Human Papillomavirus-Associated Cancers – United States, 2004-2008. MMWR Apr. 20, 2012; 61(15): 258-261.
230 ACIP Meeting Presentation – Trends in HPV-associated cancers in the United States. Dr. Elizabeth VanDyne, CDC/NCIRD. Feb. 12, 2018.
231 CDC. United States Cancer Statistics – Data Brief – Cancers associated with human papillovavirus, United States-2010-2014. No. 1. Dec. 2017.
232 FDA Gardasil 9 – Product insert. Feb. 9, 2018.
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235 FDA Gardasil – Product insert. Apr. 24, 2015.
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238 CDC. Human Papillomavirus (HPV) Vaccine Safety. Jan. 30, 2018
239 FDA. Gardasil – Product insert. Apr. 24, 2015.
240 FDA. Cervarix – Product insert. Apr. 25, 2016.
241 FDA. Gardasil 9 – Product insert. Feb. 9, 2018.
242 NVIC. Analysis Shows Greater Risk of GBS Reports When HPV Vaccine Is Given with Meningococcal and Other Vaccines. Aug. 15, 2007.
243 Brotherton JML, Gold MS. et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. CMAJ. 2008 Sep 9; 179(6): 525–533.
244 Soldevilla HF, Briones SF, Navarra SV. Systemic lupus erythematosus following HPV immunization or infection? Lupus. 2012 Feb;21(2):158-61
245 Gatto M, Agmon-Levin N. et al. Human papillomavirus vaccine and systemic lupus erythematosus. Clin Rheumatol. (2013) 32: 1301.
246 Katoulis AC, Liakou A. et al. Erythema multiforme following vaccination for human papillomavirus. Dermatology 2010;220:60–2.
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253 Álvarez-Soria MJ, Hernández-González A, et al. Demyelinating disease and vaccination of the human papillomavirus. Rev Neurol. 2011 Apr 16;52(8):472-6.
254 Sutton I, Lahoria R. et al. CNS demyelination and quadrivalent HPV vaccination. Mult Scler. 2009 Jan;15(1):116-9.
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256 Souayah N, Michas-Martin PA. et al. Guillain–Barré syndrome after Gardasil vaccination: Data from Vaccine Adverse Event Reporting System 2006–2009. Vaccine. 2011 Jan 29;29(5):886-9.
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258 Das A, Chang D. et al. Pancreatitis following human papillomavirus vaccination. Med J Aust. 2008 Aug 4;189(3):178.
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260 Miranda S, Chaignot C. et al. Human papillomavirus vaccination and risk of autoimmune diseases: A large cohort study of over 2 million young girls in France. Vaccine. 2017 Aug 24;35(36):4761-4768.
261 Debeer P, De Munter P. et al. Brachial plexus neuritis following HPV vaccination. Vaccine. 2008 Aug 18;26(35):4417-9.
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266 Ogino K, Kishi S, Yoshimura N. Multiple Evanescent White Dot Syndrome after Human Papillomavirus Vaccination. Case Rep Ophthalmol. 2014 Jan-Apr; 5(1): 38–43.
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272 Pugnet G, Ysebaert L. et al. Immune thrombocytopenic purpura following human papillomavirus vaccination. Vaccine. 2009 Jun 8;27(28):3690.
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277 Richards S, Chalkiadis G. et al. Complex regional pain syndrome following immunization. Arch Dis Child. 2012 Oct;97(10):913-5
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279 Kinoshita T, Abe RT. et al. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53(19):2185-200.
280 Martínez-Lavín M, Martínez-Martínez LA, Reyes-Loyola P. et al. HPV vaccination syndrome. A questionnaire-based study. Clin Rheumatol. 2015 Nov;34(11):1981-3.
281 Little D, Ward HR. Premature ovarian failure 3 years after menarche in a 16-year-old girl following human papillomavirus vaccination. BMJ Case Rep. Sep. 30, 2012.
282 Colafrancesco S, Perricone C. et al. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol. 2013 Oct;70(4):309-16
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286 Shoenfeld Y, Agmon-Levin N. 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011 Feb;36(1):4-8
287 Tomljenovic L, Colafrancesco S. et al. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants” Case Report and Literature Review. J Investig Med High Impact Case Rep. 2014 Jan-Mar; 2(1): 2324709614527812.
288 Colafrancesco S, Perricone C. et al. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol. 2013 Oct;70(4):309-16
289 Hotta O, Tanaka A. et al. Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). Immunol Res. 2017 Feb;65(1):66-71.
290 Poddighe D, Castelli L. et al. A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder? Immunol Res. 2014;60(2–3):236–246.
291 Palmieri B, Poddighe D. et al. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature. Immunol Res. 2017; 65(1): 106–116.
292 Pellegrino P, Perrone V. et al. The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems. Immunol Res. 2015 Feb;61(1-2):90-6.
293 Inbar R, Weiss R. et al. Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil. Immunol Res. 2017 Feb;65(1):136-149
294 Tomljenovic L, Shaw CA. Death after Quadrivalent Human Papillomavirus (HPV) Vaccination: Causal or Coincidental? Pharmaceutical Regulatory Affairs: Open Access 2012,S12:001
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296 Chandler RE. Safety Concerns with HPV Vaccines Continue to Linger: Are Current Vaccine Pharmacovigilance Practices Sufficient? Drug Saf. 2017; 40(12): 1167–1170.
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298 Joelving F. What the Gardasil Testing May Have Missed. Slate. Dec. 17, 2017.
300 EDITORIAL NOTE Statement on Corrections. Indian J Med Ethics. May 9, 2018.
301 Andersson L. Comment - RETRACTED: Increased incidence of cervical cancer in Sweden: Possible link with HPV vaccination. Indian J Med Ethics. May 26, 2018.
303 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006.
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305 Lazarus R. Electronic Support for Public Health-Vaccine Adverse Event Reporting System (ESP:VAERS). Harvard Pilgrim Health Care, Inc.
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308 Braun M. Vaccine adverse event reporting system (VAERS): usefulness and limitations. Johns Hopkins Bloomberg School of Public Health
309 Rosenthanl S, Chen R. The reporting sensitivities of two passive surveillance systems for vaccine adverse events. Am J Public Health 1995; 85: pp. 1706-9.
310 U.S. Department of Health and Human Services. National Vaccine Injury Compensation Program Data Report - updated July 1, 2018. Jul. 1, 2018.
311 Court Listener. Tarsell v. Secretary of Health and Human Services, 10-251 (Fed. Cl. 2018) United States Court of Federal Claims. Mar. 26, 2018.
312 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality: Evaluating Biological Mechanisms of Adverse Events (p. 57-102), Increased Susceptibility (p. 82). Washington, DC: The National Academies Press 2012.
313 Gatto M, Agmon-Levin N. et al. Human papillomavirus vaccine and systemic lupus erythematosus. Clin Rheumatol. (2013) 32: 1301.
314 Schofield JR, Hendrickson JE. Autoimmunity, Autonomic Neuropathy, and the HPV Vaccination: A Vulnerable Subpopulation. Clin. Pediatr. 2018 Vol 57(5) 603-606
315 CDC. HPV - Vaccine Information Sheet. Dec. 2, 2016.
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