Gardasil


Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus. It was developed by Merck & Co. High-risk human papilloma virus genital infection is the most common sexually transmitted infection among women. The HPV strains that Gardasil protects against are sexually transmitted, specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. HPV type 16 is responsible for almost 90% of HPV-positive oropharyngeal cancers, and the prevalence is higher in males than females. Though Gardasil does not treat existing infection, vaccination is still recommended for HPV-positive individuals, as it may protect against one or more different strains of the disease.
The vaccine was approved for medical use in the United States in 2006, initially for use in females aged 9–26. In 2007, the Advisory Committee on Immunization Practices recommended Gardasil for routine vaccination of girls aged 11 and 12 years. As of August 2009, vaccination was recommended for both males and females before adolescence and the beginning of potential sexual activity. By 2011, the vaccine had been approved in 120 other countries.
In 2014, the US Food and Drug Administration approved a nine-valent version, Gardasil 9, to protect against infection with the strains covered by the first generation of Gardasil as well as five other HPV strains responsible for 20% of cervical cancers. In 2018, the FDA approved expanded use of Gardasil 9 for individuals 27 to 45 years old.

Types

Gardasil is available as Gardasil which protects against 4 types of HPV and Gardasil 9 which protects against an additional 5 types.

Medical uses

In the United States, Gardasil is indicated for:
  • girls and women 9 through 45 years of age for the prevention of the following diseases:
  • * Cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by Human Papillomavirus types 16, 18, 31, 33, 45, 52, and 58.
  • * Genital warts caused by HPV types 6 and 11.
  • girls and women 9 through 45 years of age for the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58:
  • * Cervical intraepithelial neoplasia grade 2/3 and cervical adenocarcinoma in situ.
  • * Cervical intraepithelial neoplasia grade 1.
  • * Vulvar intraepithelial neoplasia grade 2 and grade 3.
  • * Vaginal intraepithelial neoplasia grade 2 and grade 3.
  • * Anal intraepithelial neoplasia grades 1, 2, and 3.
  • boys and men 9 through 45 years of age for the prevention of the following diseases:
  • * Anal, oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58.
  • * Genital warts caused by HPV types 6 and 11.
  • boys and men 9 through 45 years of age for the following precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58:
  • * Anal intraepithelial neoplasia grades 1, 2, and 3.
In the European Union, Gardasil is indicated for active immunization of individuals from the age of nine years against the following HPV diseases:
  • Premalignant lesions and cancers affecting the cervix, vulva, vagina and anus caused by vaccine HPV types
  • Genital warts caused by specific HPV types.
Gardasil is a vaccine to prevent HPV, that, for maximum effect, is recommended for individuals prior to them becoming sexually active. Moreover, women who have already been infected with one or more of the four HPV types targeted by the vaccine may be protected from clinical disease caused by the remaining HPV types in the vaccine. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal cancers. Gardasil also protects against vulvar and vaginal cancers caused by HPV types 16 and 18, as well as most penile cancers caused by these two HPV types.
In addition, protection against HPV types 6 and 11 may eliminate up to 90% of the cases of genital warts. Common plantar warts—e.g., caused by HPV types 1, 2, and 4—are not prevented by this vaccine.
In 2010, Gardasil was approved by the FDA for prevention of anal cancer and associated precancerous lesions due to HPV types 6, 11, 16, and 18 in people aged 9 through 26 years.
HPV infections, especially HPV 16, contribute to some head and neck cancer. In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated. In June 2020, the FDA approved the use of Gardasil for the prevention of head and neck cancers.
The FDA approved Gardasil 9 for women and men aged 27 to 45 based on the vaccine being 88% effective against persistent HPV infections that cause certain types genital warts and cancers in females. Vaccine efficacy in males in this age group was inferred.

Efficacy

A 2020 longitudinal study tracking over 1.6 million Swedish girls and women over an eleven-year period found half as many cervical cancer cases in all women who had been vaccinated, and amongst women who had been vaccinated before the age of 17 a 78% reduction in cervical cancer, "a substantially reduced risk of invasive cervical cancer at the population level."
An alternative vaccine known as Cervarix protects against two oncogenic strains of HPV, 16 and 18.
The National Cancer Institute says, "To date, protection against the targeted HPV types has been found to last for at least 10 years with Gardasil, at least 9 years with Cervarix, and at least 6 years with Gardasil 9. Long-term studies of vaccine efficacy that are still in progress will help scientists better understand the total duration of protection."
Gardasil has been shown to be partially effective in preventing cervical cancer caused by ten other high-risk HPV types.
Antibody levels at month 3 are substantially higher than at month 24, suggesting that protection is achieved by month 3 and perhaps earlier. In 2014, the World Health Organization recommended that countries offer the vaccine in a two dose schedule to girls aged under 15, with each dose at least six months apart. The United Kingdom, Switzerland, Mexico, and Quebec province of Canada are among the countries or territories that have implemented this as of 2015. The CDC recommended the vaccines be delivered in two shots over six months.

Males

Gardasil is also effective in males, providing protection against genital warts, anal warts, anal cancer, and some potentially precancerous lesions caused by some HPV types. Gardasil vaccine has been shown to decrease the risk of young men contracting genital warts. In the United States, the FDA approved administration of the Gardasil vaccine to males between ages 9 and 26 in 2009. The FDA approved administration of the Gardasil 9 vaccine to males between ages 9 and 15 in 2014, and extended the age indication, by including males between ages 16 and 26, in 2015. In the UK, HPV vaccines are licensed for males aged 9 to 15 and for females aged 9 to 26.
Men who have sex with men are particularly at risk for conditions associated with HPV types 6, 11, 16, and 18; diseases and cancers that have a higher incidence among MSM include anal intraepithelial neoplasias, anal cancers, and genital warts. HPV type 16 is also responsible for almost 90% of HPV-positive oropharyngeal squamous-cell carcinoma, a form of cancer that affects the mouth, tonsils, and throat; the prevalence of HPV-positive oropharyngeal cancers is higher in males than females. A 2005 study found that 95% of HIV-infected gay men also had anal HPV infection, of whom 50% had precancerous HPV-caused lesions.

Administration

Gardasil is given in three injections over six months. The second injection is two months after the first, and the third injection is six months after the first shot was administered. Alternatively, in some countries it is given as two injections with at least six months between them, for individuals aged 9 years up to and including 13 years.

Adverse effects

, more than 170 million doses of Gardasil had been distributed worldwide. The vaccine was tested in thousands of females. The US Food and Drug Administration and the US Centers for Disease Control and Prevention consider the vaccine to be safe. It does not contain mercury, thiomersal, live viruses or dead viruses, but virus-like particles, which cannot reproduce in the human body.
The vaccine has mostly minor side effects, such as pain around the injection area. Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. There have been reports that the shot is more painful than other common vaccines, and the manufacturer Merck partly attributes this to the virus-like particles within the vaccine. General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.
The FDA and the CDC said that with millions of vaccinations "by chance alone some serious adverse effects and deaths" will occur in the time period following vaccination, but they have nothing to do with the vaccine. More than twenty women who received the Gardasil vaccine have died, but these deaths have not been causally connected to the shot, as correlation does not imply causation. Where information has been available, the cause of death was explained by other factors. Likewise, a small number of cases of Guillain–Barré syndrome have been reported following vaccination with Gardasil, though there is no evidence linking GBS to the vaccine. It is unknown why a person develops GBS, or what initiates the disease.
The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone. The majority of side effects data were reported by the manufacturer, but in about 90% of the manufacturer reported events, no follow-up information was given that would be useful to investigate the event further. In February 2009, the Spanish Ministry of Health suspended use of one batch of Gardasil after health authorities in the Valencia region reported that two girls had become ill after receiving the injection. Merck has stated that there was no evidence Gardasil was responsible for the two illnesses.