When was the Papillomavirus vaccine born?

In the early 80s, 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).

Merck's Gardasil vaccine was the first FDA-approved HPV vaccine, but gained Fast Track approval from the FDA after a review process of just six months.⁽⁶⁾

Before Gardasil vaccination, cervical cancer prevention included regular Pap smears and additional treatment options, including colposcopy and removal of any abnormal lesions with techniques such as laser electrosurgical excision procedure (LEEP). These treatment options continue to be the standard of care for cervical cancer screening and prevention⁽⁷⁾ and are credited with reducing cervical cancer in the United States by 75 percent.⁽⁸⁾
Despite the availability of effective treatment options for the detection and prevention of cervical cancer, Gardasil has achieved Fast Track status and accelerated approval from the FDA.⁽⁹⁾ Accelerated approval is designed to allow drugs to be approved before they show any clinical benefit to the patient. The approval is based on findings associated with the use of a "surrogate endpoint," such as a physical marker, a laboratory finding such as antibody levels, or "another measure thought to predict clinical benefit, but does not is in itself a measure of clinical benefit."⁽¹⁰⁾ In other words, Gardasil did not have to demonstrate true efficacy – the prevention of cervical cancer – before it was deemed effective and received FDA approval and licensing.

Invasive cervical cancer caused by an unresolved HPV infection can take decades⁽¹¹⁾ to develop and, accordingly, Merck's pre-license studies on Gardasil, limited to five years,⁽¹²⁾ they could not confirm clinically that his vaccine was actually able to prevent cervical cancer.⁽¹³⁾ The FDA also allowed Merck to use amorphous aluminum hydroxyphosphate sulfate (AAHS), an aluminum adjuvant, in place of a saline placebo, as a control in prelicensure clinical trials of the original Gardasil.⁽¹⁴⁾ The safety of aluminum adjuvants in vaccines had already been questioned^(15-16-17) prior to use in HPV vaccines and ongoing research on aluminum hydroxide in vaccines has found it to be associated with long-term cognitive dysfunction^(18-19) as well as chronic pain⁽²⁰⁾ and fatigue.⁽²¹⁾ However, even in the face of studies linking aluminum to inflammation and chronic health problems, Merck was granted permission to use it as a control in pre-licensure safety studies.

On May 18, 2006, Merck submitted data to the FDA's Advisory Committee on Vaccines and Biological Products (VRBPAC) demonstrating that Gardasil prevents cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 and, consequently, the FDA has approved the vaccine for use in girls and women aged 9 to 26,^(22-23) but VRBPAC did not have clinical data confirming Gardasil's ability to prevent cervical cancer. Accordingly, a "surrogate endpoint" - the reduction in CIN 1, 2 and 3 related to HPV types 16 and 18 - was used to infer the likely efficacy of the vaccine. Using this parameter, VRBPAC concluded that the vaccine was effective even though it had not been shown to prevent cervical cancer.⁽²⁴⁾ The 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 the pre-approval studies.⁽²⁵⁾

Within weeks of Gardasil's approval by the FDA, 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" program " for women between the ages of 13 and 26.⁽²⁶⁾ Although Gardasil has been recommended for use prior to the initiation of sexual activity, even currently sexually active women have been encouraged to take it without pre-screening for current HPV infection, although pre-specified data approvals noted that the vaccine has the potential to exacerbate an ongoing HPV infection.⁽²⁸⁾ The CDC press release recommending Gardasil for routine use did not report the vaccine's inability to treat preexisting HPV infections, precancerous lesions, or cervical cancer.⁽²⁸⁾

At the time of release, Gardasil was the most expensive vaccine in history, costing an average of $360 plus the additional costs associated with doctor visits to complete the recommended three-dose series.⁽²⁹⁾ As a result, cost estimates to vaccinate all US women ages 11 to 18 have been put at $2 billion.⁽³⁰⁾

In 2005, one year before Gardasil was approved by the FDA, more than 1.500 of Merck's sales representatives were refocused to focus on the Gardasil vaccine, and Merck's contributions to women's health organizations and political campaigns increased dramatically.⁽³¹⁾
Following FDA clearance and ACIP recommendation, Merck launched a very aggressive marketing campaign targeting adolescent girls, encouraging them to be "one less victim" of cervical cancer. In addition to advertising campaigns targeting young women, Merck has initiated extensive state-level lobbying campaigns to make HPV vaccination mandatory for school entry. Merck's efforts included lobbying state legislators, drafting laws, seeking support from legislators and physicians' trade organizations, and becoming the primary source of vaccination information against the HPV.