Text Size:

What is the History of HPV Vaccine Use in America?


hpv

In the early 1980’s, studies confirmed the presence of HPV types 16 and 18 in cervical cancer cells,1 2 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.3 

Both Merck, the manufacturer of Gardasil4 and Gardasil 9,5 and GlaxoSmithKline, the manufacturer of Cervarix6 utilized new Virus-Like Particle (VLP) technology patented in 1994,7 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.8 When injected, VLPs have the ability to produce an immune response due to the presence of foreign material.9

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.10 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.”11 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 cancer12 and are credited with decreasing the U.S. cervical cancer by 75 percent.13

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.14 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.”15 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 decades16 to develop, and as a result, Merck’s pre-licensing studies of Gardasil, limited to five years,17 could not clinically confirm that its vaccine could actually prevent cervical cancer.18 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.19 The safety of aluminum adjuvants in vaccines had previously been called into question20 21 22prior to use in HPV vaccines and continued research on aluminum hydroxide in vaccines found it to be associated with long-term cognitive dysfunction23 24 in addition to chronic pain25 and fatigue.26 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 26.27 28

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.29 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.30

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.31 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 26.32 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.33 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.34

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.35 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.36

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.37

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.38 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.39

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.40

Early February 2007, Texas Governor Rick Perry signed an executive order mandating the HPV vaccine for all 6th grade girls 41 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.42 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.43 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,44 a national non-profit organization of female state legislators, received substantial contributions from Merck to direct attention on cervical cancer, HPV infections and Gardasil.45

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.46 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.47 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.48 49 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.50

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 release51 and the first of three analyses of adverse reactions reported to VAERS 52 53 54 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.55

In June 2008, Judicial Watch, a conservative, non-partisan foundation, promoting transparency, accountability and integrity in government, published a 25 page special report56 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.57

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.58 5960 61 62 63 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, 2008.64 65 While the update was intended to follow current guidelines requiring all immigrants to receive all appropriate CDC recommended vaccines, the update was criticized by many66 67 and on December 14, 2009, HPV vaccination was removed from the list of vaccines required for immigrants.68

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.69

Additionally, federal agency staff published the same information in a 2009 Journal of the American Medical Association (JAMA) article summarizing the Gardasil’s safety.70 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.71

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.72 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).73 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 11.74 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.75

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.7677

In October 2009 Cervarix,78 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.79 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).80 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 26.81 However, by October of 2016, citing low demand for its product, GlaxoSmithKline announced that Cervarix would no longer be marketed in the United States.82

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,”83 Sin Hang Lee, a Board Certified Pathologist, tested 13 different vials of Gardasil vaccine and discovered that each one contained Human Papillomavirus (HPV) DNA.84 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.85 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.86 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.87 88 89 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.90 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.91

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.92 Couric’s program resulted in an onslaught of attacks from numerous media sources accusing her of promoting junk science and fear mongering.93 94 95 96 97 98 99 100 After enduring several days of negative media stories, Couric published a blog commentary101 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.”102

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.103 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.104 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.105

Reports of serious side effects following HPV vaccination in Denmark have continued where parents are expressing concern over the vaccine’s safety.106 Ireland’s TV3 television station aired a similar documentary December 2015 profiling several girls who developed debilitating health problems following HPV vaccination.107 In 2017, Sacrificial Virgins,108 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.109 110 111

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 58.112 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 58.113 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.114

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.115 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.116 One year later, the FDA approved Gardasil 9 for use in males ages 16 to 26 in December 2015.117

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.118 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”.119

Despite Merck’s 2016 marketing campaign,120 which appears to shame parents for declining Gardasil for their children, HPV vaccination uptake rates remain low. A 2018 published report121 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.122

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.123 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.124 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.125

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.

« Return to Vaccines & Diseases Table of Contents

References

1 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.

2 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.

3FDA. Meeting transcript - Vaccines and Related Biological Products Advisory Committee (VRBPAC). Nov. 28-29, 2001.

4 FDA Gardasil – Product insert. Apr. 24, 2015

5 FDA Gardasil 9 – Product insert. Feb. 9, 2018

6 FDA Cervarix – Product insert. Apr. 26, 2016

7 Grimes JL. HPV Vaccine Development: A case study of prevention and politics. IUMBM Journals. Nov. 3. 2006

8 National Institutes of Health (NIH) NCI Dictionary of Cancer Terms - virus-like particle. National Cancer Institute. No Date.

9 Grimes JL. HPV Vaccine Development: A case study of prevention and politics. IUMBM Journals. Nov. 3. 2006

10 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

11 FDA Fast Track Jan. 4. 2018

12 National Institutes of Health (NIH) Understanding Cervical Changes: Next Steps After an Abnormal Screening Test. National Cancer Institute. Feb. 21, 2017.

13 Safaeian M, Soloman D. Cervical Cancer Prevention - Cervical Screening: Science in Evolution. Obstet Gynecol Clin North Am. 2007 Dec; 34(4): 739–ix.

14 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

15 FDA Accelerated Approval. Jan 4, 2018

16 Pubmed Health. Cervical Cancer: overview. Informed Health Online. Dec. 14, 2017

17 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.

18 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

19 FDA Gardasil – Product insert. Apr. 24, 2015

20 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.

21 Gherardi RK, Authier FJ, Aluminum inclusion macrophagic myofasciitis: a recently identified condition. Immunol Allergy Clin North Am. 2003 Nov;23(4):699-712.

22 Shingde M, Hughes J. et al. Macrophagic myofasciitis associated with vaccine-derived aluminium. Med J Aust. 2005 Aug 1;183(3):145-6.

23 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

24 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.

25 Gherardi RK, Authier FJ. Macrophagic myofasciitis: characterization and pathophysiology. Lupus. 2012 Feb;21(2):184-9

26 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

27 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006

28 FDA Center for Biologics Evaluation and Research. Summary Minutes. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006

29 FDA Gardasil – Product insert. Apr. 24, 2015

30 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006

31 NVIC. Merck’s Gardasil Vaccine Not Proven Safe for Little Girls.  June 27, 2006

32 CDC Advisory Committee on Immunization Practices. June 29-30, 2006. Atlanta Georgia. Record of the Proceedings. Jun. 29-30, 2006

33 FDA Center for Biologics Evaluation and Research. Vaccines and Related Biological Products Advisory Committee Meeting. May 18, 2006

34 CDC CDC’s Advisory Committee Recommends Human Papillomavirus Virus Vaccination. Press Release. Jun.29, 2006

35 Kotz D. 5 Things to Consider Before Getting the HPV Vaccine. U.S. News and World Report. Sep. 2, 2008

36 Harris G. Panel Unanimously Recommends Cervical Cancer Vaccine for Girls 11 and Up. New York Times. Jun 30, 2006

37 Editorial Flogging Gardasil. Nature Biotechnology 25, page 261 (2007). Mar. 1, 2007

38 Ibid

39 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.

40 Editorial Flogging Gardasil. Nature Biotechnology 25, page 261 (2007). Mar. 1, 2007

41 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

42 Elliot J. House panel votes to block HPV order - Panel votes to block HPV vaccine requirement. Houston Chronicle. Feb. 22, 2007.

43 Elliot J. Perry won’t veto bill blocking his HPV order. Houston Chronicle. May 8, 2007.

44 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.

45 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.

46 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.

47 Gardner A. Merck to Stop Pushing to Require Shots. Washington Post. Feb 21, 2007

48 Yang E. DC Requiring Girls to Get HPV Vaccine This Fall -Parents can opt out of otherwise mandatory vaccine.  NBC Washington. Aug. 11, 2009.

49 Craig T. Kaine Says He'll Sign Bill Making Shots Mandatory. Washington Post. Mar. 3, 2007.

50 Borg L. Rhode Island to mandate HPV vaccine for all 7th graders. Providence Journal. Jul. 28, 2015.

51 NVIC. HPV Vaccine Mandates Risky and Expensive.  Vaccine Safety Group Finds Serious Reactions, High Costs. HPV. Feb. 1, 2007.

52 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 1, Adverse Reactions, Concerns and Implications. Feb. 1, 2007.

53 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 2. Feb. 21, 2007.

54 NVIC. Human Papilloma Virus Vaccine Safety. Analysis of Vaccine Adverse Events Reporting System Reports Part 3. Aug. 15, 2007.

55 NVIC Analysis Shows Greater Risk of GBS Reports When HPV Vaccine Is Given with Meningococcal and Other Vaccines. Aug 15, 2007.

56 Judicial Watch. A Judicial Watch Special Report – Examining the FDA’s HPV Vaccine Records. Jun. 30, 2008.

57 Ibid

58 Edelman S. FED’S WARNING SHOT. New York Post. Jul. 6, 2008.

59 Kotz D. Is HPV Vaccine to Blame for a Teen's Paralysis? U.S. News and World Health Report. Jul. 2, 2008.

60 Ashton J. HPV Vaccine Risk. CBS Early Show. Aug. 19, 2008.

61 Attkisson S.  Is HPV Vaccine Safe? CBS Evening News. Jul. 7, 2008.

62 Edelman S. My Girl Died as a ‘Guinea Pig” for GardasilNew York Post. Jul. 20, 2008.

63 Attkisson S. Gardasil Vaccine Draws Concern. CBS Evening News. Feb. 7, 2009.

64 Jordan M. Gardasil Requirement for Immigrants Stirs Backlash. The Wall Street Journal. Oct. 1, 2008.

65 Black R. New Gardasil cervical cancer vaccination requirement for immigrants stirs controversy. New York Daily News. Oct. 24, 2008.

66 Hachey KJ, Allen RH. et al. Requiring human papillomavirus vaccine for immigrant women. Obstet Gynecol. 2009 Nov;114(5):1135-9.

67 James SD. Girl Rejects Gardasil, Loses Path to Citizenship. ABC News. Sep. 11, 2009.

68 Associated Press HPV vaccine no longer required for green cards. NBC News. Nov 16, 2009.

69 FDA Gardasil Vaccine Safety, Information from FDA and CDC on the Safety of Gardasil Vaccine. Aug. 20, 2009.

70 Slade B, Leidel L, Vellozzi C et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. Aug. 19, 2009.

71 Debold V, Hurwitz E. Adverse Events and Quadrivalent Human Papillomavirus Recombinant Vaccine. JAMA. 2009;302(24):2657-2658. doi:10.1001/jama.2009.1880.

72 FDA Oct. 16, 2009 Approval Letter – Gardasil. Oct. 16, 2009

73 FDA Clinical Review Gardasil, October 16, 2009. Sep. 29, 2009

74 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.

75 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.

76 FDA. Summary Basis for Regulatory Action - Gardasil, August 25, 2010. Aug. 25, 2010.

77 Gever J. FDA Rejects Gardasil for Older Women. MEDPAGE TODAY, Apr. 7, 2011.

78 FDA Cervarix – Product insert. Apr. 25, 2016.

79 FDA October 16, 2009 Approval Letter – Cervarix. Oct. 16, 2009.

80 FDA Cervarix – Product insert. Apr. 25, 2016.

81 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.

82 Mulcahy N. GSK’s HPV Vaccine, Cervarix, No Longer Available in US. Medscape. Oct. 24, 2016.

83 SaneVax About Us. Accessed Sep.14, 2018.

84 Botha LC. SANE Vax Discovers Potential Bio-hazard Contaminant in Merck’s Gardasil™ HPV 4 Vaccine. SANE Vax Inc. Sep. 5, 2011

85 Erickson, N. SANE Vax to FDA: Recombinant HPV DNA found in multiple samples of Gardasil. SANE Vax Inc. Sep. 2, 2011

86 FDA. FDA Information on Gardasil – Presence of DNA Fragments Expected, No Safety Risk, Oct. 21, 2011

87 Laino C. 2 ALS Cases May Be Linked to Gardasil Vaccine. WebMD. Oct. 16, 2009

88 Gonthier V. Family sues after teen dies following HPV vaccination. Toronto Sun. Jan. 31, 2012

89 Green G. Krystal’s Story. Women Hurt by Medicine. May 14, 2010

90 Mulcahy N. Japan Withdraws HPV Vaccine Recommendation for Girls. Medscape. Jun. 25, 2013

91 Chustecka Z. Class Action Lawsuit Against HPV Vaccine Filed in Japan. Medscape. Jul. 27, 2016

92 NVIC. Gardasil Vaccine, Katie Couric and Cyber-Lynching. Jan. 14, 2014

93 Hiltzik, M. Katie Couric Puts the Anti-Vaccination Movement Into the Mainstream. LA Times. Dec. 4, 2013.

94 Sifferlin A. Is Katie Couric the Next Jenny McCarthy?  Time Magazine Dec. 4, 2013

95 Blake, M. Katie Couric Under Fire for Allegedly Slanted Report on HPV VaccineLA Times Dec. 5, 2012. 

96 Marcotte A. Katie Hands Over Her Show to Anti-Vaccine AlarmistsSlate Dec. 4, 2013.

97 Monookin S. Katie Couric Promotes Dangerous Fear Mongering with Show on the HPV VaccinePLOS Blogs Dec. 3, 2013.

98 Herper M. Four Ways Katie Couric Stacked the Deck Against GardasilForbes Dec. 4, 2013.

99 Willingham E. Katie Couric Promotes Anticancer Vaccine AlarmismForbes Dec. 4, 2013.

100 McDonough K. Katie Couric Gets Called Out for Promoting Bogus Science on HPV Vaccine.Salon.com Dec. 4, 2013.

101 Couric K. Furthering the Conversation on the HPV Vaccine. Huffington Post. Dec. 10, 2013

102 Ibid

103 Erickson N.  HPV Vaccines: A Danish Documentary. SaneVax, Inc. Apr. 28, 2015

104 European Medicines Agency HPV vaccines: EMA confirms evidence does not support that they cause CRPS or POTS. Jan. 12, 2016

105 Chustecka Z. Complaint Filed Over EMA's Handling of HPV Vaccine Safety Issues. Medscape. Jul. 5, 2016

106 Gadd S. Side-effects stories affecting HPV vaccination numbers. CPHPOST Online. May 10, 2017

107 Maher D. Lives of 130 teenage girls 'ruined by cancer vaccine', families claim. Irish Mirror. Dec. 14, 2015

108 Shenton J, Reiss A. Sacrificial Virgins. Meditel Productions and Yellow Entertainment. 2017

109 CDC Frequently Asked Questions about HPV Vaccine Safety. Apr. 11, 2018

110 European Medicines Agency Gardasil Sep.18, 2017

111 European Medicines Agency Cervarix Jan. 3, 2018

112 FDA. Gardasil 9 – Product insert. Feb. 9, 2018

113 FDA. December 10, 2014 Approval Letter -GARDASIL 9. Dec. 10, 2014

114 FDA. Summary Basis for Regulatory Action – GARDASIL 9 Dec. 9, 2014

115 FDA. Gardasil 9 – Product insert. Feb. 9, 2018

116 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.

117 FDA December 14, 2015 Approval Letter – GARDASIL 9. Dec. 14, 2015.

118 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

119 FDA Gardasil 9 – Product insert. Feb. 9, 2018

120 Bulik BS. Merck holds parents accountable in new Gardasil ad campaign. Fierce Pharma. Jun. 28, 2016

121 BCBS Adolescent vaccination rates in America. The Health Of America.  Feb. 13, 2018.

122 PR Newswire Blue Cross Blue Shield Association Study Shows Low Uptake of HPV Vaccine Compared to Other Adolescent Immunizations. Feb. 13, 2018

123 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.

124 National Institutes of Health (NIH) Pap and HPV Testing. National Cancer Institute. Sep. 9, 2014

125 ACIP Meeting Presentation – Trends in HPV-associated cancers in the United States. Dr. Elizabeth VanDyne, CDC/NCIRD. Feb. 12, 2018.


Make a Difference Support NVIC

NVIC is 100% funded by donations.
Please give.

Help educate families about preventing vaccine injury and death by donating to NVIC today.

Discover How You Can Take Action to Support Our Efforts

Support NVIC!


Connect with us!

  • NVIC Pinterest
  • NVIC Facebook
  • NVIC Twitter
  • NVIC Youtube
  • NVIC Instagram

Ask 8 Kiosk & Educational Marketplace

Ask 8 Questions

Visit our Ask 8 Kiosk to explore a variety of FREE educational materials, from posters and brochures to embeddable web graphics and other resources.

View FREE Downloads