Gardasil

From Wikipedia, the free encyclopedia
  (Redirected from Gardisil)
Jump to navigation Jump to search
Gardasil
Gardasil vaccine and box new.jpg
Vaccine description
Target diseasehuman papillomavirus (Types 16, 18, 6, and 11)
TypeProtein subunit
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa607016
Pregnancy
category
  • US: B (No risk in non-human studies)
Routes of
administration
Intramuscular injection
ATC code
Legal status
Legal status
Identifiers
ChemSpider
  • none
 ‹See TfM›☒N☑Y (what is this?)  (verify)
Gardasil

Gardasil, also known as Gardisil or Silgard or recombinant human papillomavirus vaccine [types 6, 11, 16, 18],[1][2] is a vaccine for use in the prevention of certain strains of human papillomavirus (HPV),[3] specifically HPV types 6, 11, 16 and 18.[4][5] HPV types 16 and 18 cause an estimated 70% of cervical cancers,[6][7] and are responsible for most HPV-induced anal,[8] vulvar, vaginal,[9] and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. In addition, high-risk human papilloma virus (hr-HPV) genital infection is the most common sexually transmitted infection among women[10]. 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.[11] The HPV strains that Gardasil protects against are sexually transmitted.

The vaccine was approved in the US in June 2006 by the U.S. Food and Drug Administration (FDA). The FDA approved the use of Gardasil for use in girls and women aged 9-26 [12]In 2011, the Gardasil vaccine has also been approved in 120 other countries.[13] The FDA recommends vaccination before adolescence and potential sexual activity.[4][14][15]

In 2007, the Advisory Committee on Immunization Practices (ACIP) recommended gardasil for routine vaccination of girls aged 11 and 12 years[16]

In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, 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 (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).[17] In October 2018, the FDA approved expanded use of Gardasil 9 to include individuals 27 through 45 years old.[18]

Medical uses[edit]

Gardasil is a prophylactic HPV vaccine, meaning that it is designed to prevent HPV infections. For maximum effect, it is recommended that girls receive the vaccine prior to becoming sexually active. However, women who were already infected with one or more of the four HPV types targeted by the vaccine (6, 11, 16, or 18) were protected from clinical disease caused by the remaining HPV types in the vaccine. Common plantar warts are caused by HPV 1, 2 and 4,[19] which are not prevented by this vaccine.

Since Gardasil will not block infection with all of the HPV types that can cause cervical cancer, the vaccine should not be considered a substitute for routine pap smears.

Fewer HPV infections mean fewer complications from the virus and less time and money spent on the detection, work-up, and treatment of cervical cancer and its precursor, cervical dysplasia. It prevents infertility caused by cervical biopsies and reduces the severe respiratory problems of children who are infected by HPV from their mothers.

In addition, protection against HPV 6 and HPV 11 is expected to eliminate 90% of the cases of genital warts. Gardasil also protects against vulvar and vaginal cancers caused by HPV types 16 and 18.[9]

In December 2010, Gardasil was approved by the FDA for prevention of anal cancer and associated precancerous lesions due to human papillomavirus (HPV) types 6, 11, 16, and 18 in people ages 9 through 26 years.[20]

HPV infections, especially HPV 16, contribute to some head and neck cancer (HPV is found in an estimated 26-35% of head and neck squamous cell carcinoma).[21][22] In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated.[23]

FDA approved Gardasil 9 for women and men aged 27 to 45. In a large, longitudinal study of women in this age group (n=3200), the vaccine was found to be 88% effective against persistent HPV infections that cause certain types genital warts and cancers. Vaccine efficacy for men in this age group was inferred. [24]

Efficacy[edit]

An alternative vaccine known as Cervarix is manufactured by GlaxoSmithKline.[25] It protects against two oncogenic strains of HPV, 16 and 18.

The National Cancer Institute says, "Gardasil and Cervarix have been shown to provide protection against persistent cervical HPV 16/18 infections for up to 8 years, which is the maximum time of research follow-up thus far...HPV vaccination has also been found to prevent nearly 100 percent of the precancerous cervical cell changes that would have been caused by HPV 16/18. The data so far show duration of protection for up to 6.4 years with Cervarix and for up to 5 years for Gardasil—in women who were not infected with HPV at the time of vaccination."[26]

Gardasil has been shown to be partially effective (approximately 38%) in preventing cervical cancer caused by ten other high-risk HPV types.[27]

Antibody levels at month 3 (1 month postdose 2) are substantially higher than at month 24 (18 months postdose 3), suggesting that protection is achieved by month 3 and perhaps earlier.[14][28] This does not imply that the third dose can be skipped.[citation needed] One study has shown that Cervarix may be effective with fewer than three doses.[29] Following further studies, in April 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.[30] The United Kingdom, Switzerland, Mexico and Quebec are among the few countries or territories to have implemented this as at June 2015. The CDC recommends the vaccines be delivered in two shots over six months.[31]

Males[edit]

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.[5][32] Gardasil vaccine has been shown to significantly decrease the risk of young men contracting genital warts.[33] In the United States, the U.S. Food and Drug Administration (FDA) approved administration of the Gardasil vaccine to males between ages 9 and 26 in October 2009.[34][35] The FDA approved administration of the Gardasil 9 vaccine to males between ages 9 and 15 in December 2014 and extended the age indication, by including males between ages 16 and 26, in December 2015.[36][37][38] In the UK, HPV vaccines are licensed for males aged 9 to 15 and for females aged 9 to 26.[39]

Men who have sex with men (MSM) 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. Type 16 is also associated with oropharyngeal squamous-cell carcinoma, a form of throat cancer.[40] A 2005 study in San Francisco found that 95% of HIV-infected gay men also had anal HPV infection, of whom 50% had precancerous HPV-caused lesions.[41]

Administration[edit]

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.[4][14] 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.[42]

Adverse effects[edit]

As of April 2014, more than 170 million doses of Gardasil had been distributed worldwide.[43] The vaccine was tested in thousands of females (ages 9 to 26).[44] The Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) 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.[44]

Long-term side effects from the Gardasil vaccine are yet to be determined or confirmed due to the relatively short time that it has been available to the public. [45] Publications of FDA and the CDC state that the vaccine has mostly minor side effects, such as soreness around the injection area.[44] 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.[46] 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.[47] General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.[46][48]

Due to the lack of research on long-term side effects from gardasil, another area of concern is the biological responses to the vaccination itself [45]. Researchers question how the vaccine will affect young girls hormones entering puberty, or if the vaccine will prevent the bodies natural defences against infection[49]

An update on adverse events was published by the Journal of the American Medical Association and looked at data from the Vaccine Adverse Event Reporting System (VAERS), covering 12,424 reported adverse events after about 23 million doses of vaccine between June 2006 and December 2008.[50][51] Most adverse effects were minor and not greater than background rates compared with other vaccines, the exception being higher rates for syncope and thromboembolic events.[51] Venous thromboembolic events were noted in 56 reports at a rate of 0.2 cases per 100,000 doses distributed and included 19 cases of pulmonary embolism, four of which were fatal.[51] Overall, 772 events (6.2% of the total number of adverse events but only 0.003% of the total number of doses) were described as serious and included 32 reported deaths (1 per 1,000,000 doses).[51]

Other adverse events include local site reactions (7.5 cases per 100,000 doses distributed), headaches (4.1 cases per 100,000 doses distributed), hypersensitivity reactions (3.1 cases per 100,000 doses distributed), and urticaria (hives) (2.6 cases per 100,000 doses distributed).[51] A Kaiser Permanente study tracking 190,000 girls and women post-vaccination for two years found that rates of the autoimmune disorders lupus, rheumatoid arthritis, juvenile rheumatoid arthritis, idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, multiple sclerosis, thyroiditis and type 1 diabetes mellitus in vaccinated populations were the same as in unvaccinated populations.[52] 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.[53] More than twenty women who received the Gardasil vaccine have died, but these deaths have not been causally connected to the shot.[53] Where information has been available, the cause of death was explained by other factors.[54][55] Likewise, a small number of cases of Guillain–Barré syndrome (GBS) have been reported following vaccination with Gardasil, though there is no evidence linking GBS to the vaccine.[15][50][56] It is unknown why a person develops GBS, or what initiates the disease.[57]

The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone.[54] The majority (68%) 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.[51] 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.[58]

Ingredients[edit]

Biotechnology[edit]

The HPV major capsid protein, L1, can spontaneously self-assemble into virus-like particles (VLPs) that resemble authentic HPV virions. Gardasil contains recombinant VLPs assembled from the L1 proteins of HPV types 6, 11, 16 and 18. Since VLPs lack the viral DNA, they cannot induce cancer. They do, however, trigger an antibody response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine. The L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs.[59]

Public health[edit]

The National Cancer Institute writes:

Widespread vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds, if all women were to take the vaccine and if protection turns out to be long-term. In addition, the vaccines can reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up from abnormal Pap tests, thus helping to reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures.[26]

Long-term impact and cost-effectiveness[edit]

Whether the effects are temporary or lifelong, widespread vaccination could have a substantial public health impact. As of 2018, studies have proven that cervical cancer rates have dropped significantly since the introduction of Gardasil. [60] Before Gardasil was introduced in 2006, 270,000 women died of cervical cancer worldwide in 2002.[61] As of 2014, the mortality rate from cervical cancer has dropped 50% from 1975 which is due to the Gardasil vaccination along with increased focus on cervical screening. [62]Acting FDA Administrator Andrew von Eschenbach said the vaccine will have "a dramatic effect" on the health of women around the world.[63] Gardasil is an important tool in reducing cervical cancer rates even in countries where screening programs are routine. The National Cancer Institute estimated that 9,700 women would develop cervical cancer in 2006, and 3,700 would die.[64]

Merck and CSL Limited are expected to market Gardasil as a cancer vaccine, rather than an STD vaccine. In the early years of Gardasil's introduction it was unclear how widespread the use of the three-shot series would be, in part because of its $525 list price ($175 each for three shots).[65] But as of 2013, vaccine coverage has been rising.[60] In 2013, about 55% of girls ages 13-17 years had at least one dose of the vaccination covered, up from 29% in 2007. Coverage for women ages 18-34 also has increased significantly since 2007.[60]

Studies using different pharmacoeconomic models predict that vaccinating young women with Gardasil in combination with screening programs may be more cost effective than screening alone.[66] These results have been important in decisions by many countries to start vaccination programs.[67] For example, the Canadian government approved $300 million to buy the HPV vaccine in 2008 after deciding from studies that the vaccine would be cost-effective especially by immunizing young women.[68] Marc Steben, an investigator for the vaccine, wrote that the financial burden of HPV related cancers on the Canadian people was already $300 million per year in 2005, so the vaccine could reduce this burden and be cost-effective.[69]

Since penile and anal cancers are much less common than cervical cancer, HPV vaccination of young men is likely to be much less cost-effective than for young women.[53]

The August 2009 issue of the Journal of the American Medical Association had an article reiterating the safety of Gardasil[50] and another questioning the way it was presented to doctors and parents.

The new vaccine against 4 types of human papillomavirus (HPV), Gardasil, like other immunizations appears to be a cost-effective intervention with the potential to enhance both adolescent health and the quality of their adult lives. However, the messages and the methods by which the vaccine was marketed present important challenges to physician practice and medical professionalism. By making the vaccine's target disease cervical cancer, the sexual transmission of HPV was minimized, the threat of cervical cancer to adolescents was maximized, and the subpopulations most at risk practically ignored. The vaccine manufacturer also provided educational grants to professional medical associations (PMAs) concerned with adolescent and women's health and oncology. The funding encouraged many PMAs to create educational programs and product-specific speakers' bureaus to promote vaccine use. However, much of the material did not address the full complexity of the issues surrounding the vaccine and did not provide balanced recommendations on risks and benefits. As important and appropriate as it is for PMAs to advocate for vaccination as a public good, their recommendations must be consistent with appropriate and cost-effective use.[70]

According to the CDC, as of 2012, use of the HPV vaccine had cut rates of infection with HPV-6, -11, -16 and -18 in half in American teenagers (from 11.5% to 4.3%) and by one third in American women in their early twenties (from 18.5% to 12.1%).[71]

History[edit]

Research findings that pioneered the development of the vaccine began in 1991 by investigators Jian Zhou and Ian Frazer in The University of Queensland, Australia. Researchers at UQ found a way to form non-infectious virus-like particles (VLP), which could also strongly activate the immune system. Subsequently, the final form of the vaccine was developed in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute.[72]

In December 2014, the FDA approved Gardasil-9, which protects against 9 strains of HPV.[73]

Society and culture[edit]

United States[edit]

The governor of Texas, Rick Perry, issued an executive order adding Gardasil to the state's required vaccination list, which was later overturned by the Texas legislature. Perry has also allowed parents to opt out of the program more easily. Through lobbying efforts, Merck has suggested that state governments make vaccination with Gardasil mandatory for school attendance,[74] which has upset some conservative and libertarian groups.[63][75][76] A few conservative groups, such as the Family Research Council (FRC), have expressed their fears that vaccination with Gardasil might give girls a false sense of security regarding sex and lead to promiscuity,[63][76][77][78] but no evidence exists to suggest that girls who were vaccinated went on to engage in more sexual activity than unvaccinated girls.[79] Those who oppose a Gardasil vaccination requirement for young, school aged girls are concerned that it may lead to a decrease in their sexual inhibitions and an increase in their sexual risk taking. People who oppose the requirement would also suggest that adolescents do not fully understand what Gardasil protects against.[45] Gardasil does not protect from other sexually transmitted infections, so the risk of teenagers experiencing a decrease in sexual inhibitions due to the false sense of protection from the vaccination could be harmful.[45]

Perry's decision was later criticized on September 12, 2011 by fellow presidential candidates Rick Santorum and Michele Bachmann during the Republican Party presidential debate as being an overreach of state power in a decision properly left to parents.[80]

Japan[edit]

In June 2013, the Japanese government issued a notice that "cervical cancer vaccinations should no longer be recommended for girls aged 12 to 16" while an investigation is conducted into certain adverse events including pain and numbness in 38 girls.[81] The vaccines sold in Japan are Cervarix, made by GlaxoSmithKline of the United Kingdom, and Gardasil, made by Merck Sharp & Dohme. An estimated 3.28 million people have received the vaccination; 1,968 cases of possible side effects have been reported.[82] In January 2014, the Vaccine Adverse Reactions Review Committee concluded that there was no evidence to suggest a causal association between the HPV vaccine and the reported adverse events, but did not reinstate proactive recommendations for its use.[83] A study on girls in Sapporo showed that since the Japanese government's suspension of recommending the vaccine, completion rates for the full course of vaccination have dropped to 0.6%.[83]

References[edit]

  1. ^ "Silgard European Public Assessment Report". European Medicines Agency. September 25, 2009. Archived from the original on December 25, 2008. Retrieved 2009-12-05.
  2. ^ Waknine Y (October 2, 2006). "International Approvals: Singulair and Gardasil/Silgard". Medscape Today. Archived from the original on May 20, 2013. Retrieved 2008-12-18.
  3. ^ Richwine L (August 20, 2009). "U.S. health officials back safety of Merck vaccine". Reuters. Archived from the original on August 27, 2009. Retrieved 2009-11-12.
  4. ^ a b c Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER (March 2007). "Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR. Recommendations and Reports. 56 (RR-2): 1–24. PMID 17380109. Archived (PDF) from the original on 2015-09-24.
  5. ^ a b "FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR. Morbidity and Mortality Weekly Report. 59 (20): 630–2. May 2010. PMID 20508594. Archived (PDF) from the original on 2015-09-24.
  6. ^ Lowy DR, Schiller JT (May 2006). "Prophylactic human papillomavirus vaccines". The Journal of Clinical Investigation. 116 (5): 1167–73. doi:10.1172/JCI28607. PMC 1451224. PMID 16670757. Archived from the original on 2008-12-29.
  7. ^ Muñoz N, Bosch FX, Castellsagué X, Díaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ (August 2004). "Against which human papillomavirus types shall we vaccinate and screen? The international perspective". International Journal of Cancer. 111 (2): 278–85. doi:10.1002/ijc.20244. PMID 15197783.
  8. ^ Cortez MF, Pettypiece S (13 November 2008). "Merck Cancer Shot Cuts Genital Warts, Lesions in Men". Bloomberg News. Retrieved 2009-11-12.
  9. ^ a b "FDA Approves Expanded Uses for Gardasil to Include Preventing Certain Vulvar and Vaginal Cancers" (Press release). U.S. Food and Drug Administration (FDA). 2008-09-12. Archived from the original on 2010-03-06. Retrieved 2009-11-11.
  10. ^ Gizzo, Salvatore (September 2013). "Gardasil administration to hr-HPV-positive women and their partners". Scholars Portal. 34.
  11. ^ "The Ethics of Vaccination". Springer Publishing Company. Retrieved 2013-09-29.
  12. ^ "Gardasil". Britannica Academic. April 2018.
  13. ^ Haupt RM, Sings HL (November 2011). "The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil". The Journal of Adolescent Health. 49 (5): 467–75. doi:10.1016/j.jadohealth.2011.07.003. PMID 22018560.
  14. ^ a b c d "Gardasil full prescribing information" (PDF). Merck & Co. Archived (PDF) from the original on 2012-03-18. Retrieved 2009-11-11.
  15. ^ a b "Gardasil Vaccine Safety". Vaccine Safety & Availability. U.S. Food and Drug Administration (FDA). August 20, 2009. Archived from the original on November 15, 2009. Retrieved 2009-11-11.
  16. ^ Moro, Pedro (2014). "Safety of quadrivalent human papillomavirus vaccine (Gardasil®) in pregnancy". Scholars Portal.
  17. ^ "FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV" (press release). 10 December 2014. Archived from the original on 10 January 2015. Retrieved 28 February 2015.
  18. ^ "FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old". fda.gov (Press release). October 5, 2018. Retrieved October 5, 2018.
  19. ^ "Humanitas Papiloma Virus". Archived from the original on 28 February 2017. Retrieved 26 February 2018.
  20. ^ "FDA: Gardasil approved to prevent anal cancer" (Press release). U.S. Food and Drug Administration (FDA). December 22, 2010. Archived from the original on December 18, 2014. Retrieved 2011-01-04.
  21. ^ Goon PK, Stanley MA, Ebmeyer J, Steinsträsser L, Upile T, Jerjes W, Bernal-Sprekelsen M, Görner M, Sudhoff HH (October 2009). "HPV & head and neck cancer: a descriptive update". Head & Neck Oncology. 1 (1): 36. doi:10.1186/1758-3284-1-36. PMC 2770444. PMID 19828033. Archived from the original on 2011-03-18.
  22. ^ Vousden KH (1994). Cell transformation by human papillomaviruses. Viruses and Cancer. New York: Press Syndicate of the University of Cambridge. pp. 27–46. ISBN 9780521454728.
  23. ^ Masters C (May 11, 2007). "Oral Sex Can Add to HPV Cancer Risk". Time. Archived from the original on May 14, 2009.
  24. ^ "FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old". Food & Drug Administration. 5 October 2018. Retrieved 9 October 2018.
  25. ^ "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. Morbidity and Mortality Weekly Report. 59 (20): 626–9. May 2010. PMID 20508593. Archived from the original on 2017-09-12.
  26. ^ a b "Human Papillomavirus (HPV) Vaccines". National Cancer Institute (NCI). 2009-10-22. Archived from the original on 2014-07-04. Retrieved 2009-11-11.
  27. ^ Schieszer J (November 2007). "HPV Vaccine Protects Against 10 "Other" Strains". Internal Medicine World Report. Archived from the original on 2008-12-04.
  28. ^ Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsagué X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF, Reisinger KS (November 2006). "Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women". Pediatrics. 118 (5): 2135–45. doi:10.1542/peds.2006-0461. PMID 17079588. Archived from the original on 2015-06-22.
  29. ^ Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, González P, Solomon D, Jiménez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S (October 2011). "Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine". Journal of the National Cancer Institute. 103 (19): 1444–51. doi:10.1093/jnci/djr319. PMC 3186781. PMID 21908768.
  30. ^ World Health Organization (April 2014). "Summary of the SAGE April 2014 meeting". Archived from the original on 31 July 2015. Retrieved 2 June 2015.
  31. ^ "CDC recommends only two HPV shots for younger adolescents". Centers for Disease Control and Prevention. Archived from the original on March 23, 2017. Retrieved October 7, 2017.
  32. ^ Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, Vardas E, Moi H, et al. (February 2011). "Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males". The New England Journal of Medicine. 364 (5): 401–11. doi:10.1056/NEJMoa0909537. PMC 3495065. PMID 21288094. Lay summary.
  33. ^ "Gay men seeking HPV vaccine". Cancer Research UK. 23 February 2007. Archived from the original on 24 March 2010. Retrieved 2009-11-12.
  34. ^ "FDA Approves New Indication for Gardasil to Prevent Genital Warts in Men and Boys" (Press release). U.S. Food and Drug Administration (FDA). 2009-10-16. Archived from the original on 2009-10-24. Retrieved 2009-11-12.
  35. ^ "October 16, 2009 Approval Letter – Gardasil". U.S. Food and Drug Administration (FDA). October 16, 2009. Archived from the original on October 24, 2009. Retrieved 2009-11-12.
  36. ^ "FDA licensure of 9-valent human papillomavirus vaccine to include males aged 16–26 years" (PDF). U.S. Centers for Disease Control and Prevention (CDC). 2015-12-14. Archived (PDF) from the original on 2017-01-30. Retrieved 2016-10-10.
  37. ^ "Provider Information: Gardasil® 9 VIS" (PDF). U.S. Centers for Disease Control and Prevention (CDC). December 2015. Archived (PDF) from the original on 2017-02-11. Retrieved 2016-10-10.
  38. ^ "Highlights of Prescribing InformationI: Gardasil® 9" (PDF). U.S. Food and Drug Administration (FDA). 2015-12-14. Archived (PDF) from the original on 2016-10-10. Retrieved 2016-10-10.
  39. ^ Roberts M (2007-02-23). "Gay men seek 'female cancer' jab". BBC News. Archived from the original on 2009-01-30. Retrieved 2009-11-12.
  40. ^ D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (May 2007). "Case-control study of human papillomavirus and oropharyngeal cancer". The New England Journal of Medicine. 356 (19): 1944–56. doi:10.1056/NEJMoa065497. PMID 17494927. Archived from the original on May 12, 2007.
  41. ^ Edwin J. Bernard (August 29, 2005). "HAART is not reducing risk of anal cancer in gay men". AIDSmap. Archived from the original on June 19, 2006. Retrieved 2006-06-08.
  42. ^ electronic Medicines Compendium (9 December 2014). "Gardasil". Archived from the original on 24 October 2015. Retrieved 2 June 2015.
  43. ^ Donald G McNeil Jr for the New York Times. March 31, 2014 Expansion in Use Of Cancer Vaccine Archived 2016-02-06 at the Wayback Machine.
  44. ^ a b c "HPV Vaccine Information For Young Women". Centers for Disease Control and Prevention (CDC). Archived from the original on 2009-06-28. Retrieved 2009-06-14.
  45. ^ a b c d McMahon, Wendy (2009). "Should the administration of the HPV vaccine Gardasil be mandated for young girls entering the sixth grade?". ProQuest.
  46. ^ a b c "Gardasil Patient Product Information" (PDF). Merck & Co. Archived (PDF) from the original on 2012-03-18. Retrieved 2009-11-11.
  47. ^ Mike Stobbe (January 3, 2008). "Cervical cancer shots are gaining reputation as painful". ABC News. Associated Press.
  48. ^ Amy Fagan (10 July 2008). "Merck, FDA expand Gardasil warnings". The Washington Times. Archived from the original on 17 July 2008.
  49. ^ Haug, Charlotte (2008). "Human Papillomavirus Vaccination -- Reasons for Caution". ProQuest.
  50. ^ a b c Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J (August 2009). "Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine". JAMA. 302 (7): 750–7. doi:10.1001/jama.2009.1201. PMID 19690307. Archived from the original on 2010-12-02.
  51. ^ a b c d e f Chustecka Z. (August 18, 2009). "HPV Vaccine: Debate Over Benefits, Marketing, and New Adverse Event Data". Medscape Today. Archived from the original on November 14, 2010. Retrieved 2009-08-27.
  52. ^ Klein NP, Hansen J, Chao C, Velicer C, Emery M, Slezak J, Lewis N, Deosaransingh K, Sy L, Ackerson B, Cheetham TC, Liaw KL, Takhar H, Jacobsen SJ (December 2012). "Safety of quadrivalent human papillomavirus vaccine administered routinely to females". Archives of Pediatrics & Adolescent Medicine. 166 (12): 1140–8. doi:10.1001/archpediatrics.2012.1451. PMID 23027469. Archived from the original on 2017-04-29.
  53. ^ a b c Rosenthal E (2008-08-19). "Drug Makers' Push Leads to Cancer Vaccines' Fast Rise". The New York Times. Archived from the original on 2009-04-09. Retrieved 2008-08-20.
  54. ^ a b "Information from FDA and CDC on Gardasil and its Safety (Archived)". Centers for Disease Control and Prevention (CDC). July 22, 2008. Archived from the original on September 2, 2013.
  55. ^ "Reports of Health Concerns Following HPV Vaccination". Centers for Disease Control and Prevention (CDC). October 26, 2010. Archived from the original on September 17, 2013.
  56. ^ "HPV Vaccine – Questions & Answers for the Public". 2008-07-18. Archived from the original on 2008-03-06. Retrieved 2008-08-22.
  57. ^ "Guillain–Barré Syndrome Fact Sheet". National Institute of Neurological Disorders and Stroke (NINDS). May 6, 2010. Archived from the original on August 5, 2016.
  58. ^ "Spain halts batch of Merck's Gardasil". Reuters. February 10, 2009. Archived from the original on February 13, 2009. Retrieved 2009-02-10.
  59. ^ Merck Canada Inc. "Gardasil Product Monograph" (PDF). Archived from the original (PDF) on 2014-02-24. Retrieved 2013-02-20.
  60. ^ a b c Jenco, Melissa (August 9, 2018). "Cervical cancer declines follow HPV vaccine introduction". AAP News.
  61. ^ Cohen J (April 2005). "Public health. High hopes and dilemmas for a cervical cancer vaccine". Science. 308 (5722): 618–21. doi:10.1126/science.308.5722.618. PMID 15860602.
  62. ^ "Cervical Cancer: Statistics". January 2018.
  63. ^ a b c "FDA approves first vaccine for cervical cancer". msnbc.com. Associated Press. June 16, 2006. Archived from the original on February 19, 2011. Retrieved 2006-06-08.
  64. ^ SEER Stat Fact Sheets: Cervix Uteri Archived 2014-07-06 at the Wayback Machine.. National Cancer Institute. Retrieved 30 March 2007.
  65. ^ "Health Blue Book". Retrieved 2012-08-15.
  66. ^ Stanley M (November 2007). "Prevention strategies against the human papillomavirus: the effectiveness of vaccination". Gynecologic Oncology. 107 (2 Suppl 1): S19–23. doi:10.1016/j.ygyno.2007.07.068. PMID 17938013.
  67. ^ Pallecaros A, Vonau B (December 2007). "Human papilloma virus vaccine--more than a vaccine". Current Opinion in Obstetrics & Gynecology. 19 (6): 541–6. doi:10.1097/GCO.0b013e3282f1a91b. PMID 18007131.
  68. ^ Morris SK, Nguyen CK (2008). "The human papillomavirus vaccine in Canada". Canadian Journal of Public Health = Revue Canadienne De Sante Publique. 99 (2): 114–6. PMID 18457284.
  69. ^ Steben M (March 2008). "Rebuttal: Do you approve of spending $300 million on HPV vaccination? Yes". Canadian Family Physician Medecin De Famille Canadien. 54 (3): 342, 344. PMC 2278341. PMID 18337521.
  70. ^ Rothman SM, Rothman DJ (August 2009). "Marketing HPV vaccine: implications for adolescent health and medical professionalism". JAMA. 302 (7): 781–6. doi:10.1001/jama.2009.1179. PMID 19690311. Archived from the original on 2009-10-21.
  71. ^ Haelle, Tara (February 23, 2016). "HPV Infection Rates Plummet In Young Women Due To Vaccine". Forbes. Archived from the original on February 26, 2016. Retrieved February 23, 2016.
  72. ^ McNeil C (April 2006). "Who invented the VLP cervical cancer vaccines?". Journal of the National Cancer Institute. 98 (7): 433. doi:10.1093/jnci/djj144. PMID 16595773. Archived from the original on 2014-02-26.
  73. ^ "FDA Approves Merck's HPV Vaccine, GARDASIL®9, to Prevent Cancers and Other Diseases Caused by Nine HPV types – Including Types that Cause About 90% of Cervical Cancer Cases - Merck Newsroom Home". www.mrknewsroom.com. Archived from the original on 2017-10-27.
  74. ^ Pollack, Andrew; Saul, Stephanie (21 February 2007). "Merck to halt lobbying for vaccine for girls". New York Times. Retrieved 4 July 2018.
  75. ^ Houppert K (March 26, 2007). "Who's Afraid of Gardasil?". The Nation. Retrieved 2009-11-11.
  76. ^ a b Danny Fortson (11 June 2006). "Moral majority take on GSK and Merck over cancer drugs". The Independent. Archived from the original on 14 June 2006. Retrieved 2006-06-12.
  77. ^ Barillas M (2006-09-14). "Gardasil vaccine touted in Michigan". Spero News. Archived from the original on 2006-11-14. Retrieved 2007-01-26.
  78. ^ Gaul M (2007). "Gardasil: What Parents should know about the new HPV vaccine" (PDF). Family Research Council. Retrieved 2011-09-13.
  79. ^ Bednarczyk RA, Davis R, Ault K, Orenstein W, Omer SB (November 2012). "Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds". Pediatrics. 130 (5): 798–805. doi:10.1542/peds.2012-1516. PMID 23071201.
  80. ^ Gabriel T, Grady D (2011-09-13). "In Republican Race, a Heated Battle Over the HPV Vaccine". New York Times. Archived from the original on 2011-09-14. Retrieved 2011-09-14.
  81. ^ Japan Times. (16 June 2013). "Cervix vaccine issues trigger health notice Archived 2013-12-03 at the Wayback Machine.." Accessed 9 July 2013.
  82. ^ The Asahi Shimbun. (15 June 2013). "Health ministry withdraws recommendation for cervical cancer vaccine Archived June 19, 2013, at the Wayback Machine.." Accessed 9 July 2013.
  83. ^ a b Hanley SJ, Yoshioka E, Ito Y, Kishi R (June 2015). "HPV vaccination crisis in Japan". Lancet. 385 (9987): 2571. doi:10.1016/S0140-6736(15)61152-7. PMID 26122153.

Further reading[edit]

External links[edit]