| 词条 | Gardasil |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 448706716 | image = Gardasil vaccine and box new.jpg | type = vaccine | target = human papillomavirus (Types 16, 18, 6, and 11) | vaccine_type = protein subunit | tradename = | Drugs.com = {{drugs.com|monograph|human-papillomavirus-vaccine}} | MedlinePlus = a607016 | pregnancy_AU = | pregnancy_US = B | legal_AU = | legal_CA = | legal_UK = | legal_US = Rx-only | routes_of_administration = Intramuscular injection | ATC_prefix = J07 | ATC_suffix = BM01 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = none }} 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.[9] 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.[10] 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 [11] In 2011, the Gardasil vaccine has also been approved in 120 other countries.[12] The FDA recommends vaccination before adolescence and potential sexual activity.[4][15][13] In 2007, the Advisory Committee on Immunization Practices (ACIP) recommended gardasil for routine vaccination of girls aged 11 and 12 years.[14] 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).[15] In October 2018, the FDA approved expanded use of Gardasil 9 to include individuals 27 through 45 years old.[16] Medical uses{{See also|HPV vaccine#Prevalence of genital HPV}}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,[17] which are not prevented by this vaccine. Since Gardasil will not prevent 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, known as laryngeal papillomatosis. 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.[18] In December 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 ages 9 through 26 years.[19] 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).[20][21] In principle, HPV vaccines may help reduce incidence of such cancers caused by HPV, but this has not been demonstrated.[22] The 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.[23] EfficacyAn alternative vaccine known as Cervarix is manufactured by GlaxoSmithKline.[24] 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."[28] Gardasil has been shown to be partially effective (approximately 38%) in preventing cervical cancer caused by ten other high-risk HPV types.[25] Antibody levels at month 3 (1 month post-dose number two) are substantially higher than at month 24 (18 months post-dose number three), suggesting that protection is achieved by month 3 and perhaps earlier.[15][26] This does not imply that the third dose can be skipped.{{citation needed|date=January 2013}} One study has shown that Cervarix may be effective with fewer than three doses.[27] 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.[28] 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.[29] MalesGardasil 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][30] Gardasil vaccine has been shown to significantly decrease the risk of young men contracting genital warts.[31] In the US, the FDA approved administration of the Gardasil vaccine to males between ages 9 and 26 in October 2009.[32][33] 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.[34][35][36] In the UK, HPV vaccines are licensed for males aged 9 to 15 and for females aged 9 to 26.[37] 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.[38] 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.[39]AdministrationGardasil 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][40] 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.[41] Adverse effectsOverall, the HPV vaccine has a good safety record and causes no serious adverse effects.[42] {{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]The vaccine has mostly minor side effects, such as pain 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.[54] 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.[45] General side effects of the shot may include joint and muscle pain, fatigue, physical weakness and general malaise.[54][46] 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.[47] 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.[47] Where information has been available, the cause of death was explained by other factors.[48][49] 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.[13][50][51] It is unknown why a person develops GBS, or what initiates the disease.[52] The FDA and the CDC monitor events to see if there are patterns, or more serious events than would be expected from chance alone.[48] 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.[53] 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.[54] Ingredients{{update|date=October 2017}}
BiotechnologyThe 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.[56] Public health{{Main|HPV vaccines}}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.[57] Long-term impact and cost-effectiveness{{Update|date=July 2009}}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.[58] Before Gardasil was introduced in 2006, 270,000 women died of cervical cancer worldwide in 2002.[59] 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.[60] Acting FDA Administrator Andrew von Eschenbach said the vaccine will have "a dramatic effect" on the health of women around the world.[61] 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.[62] 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).[63] But as of 2013, vaccine coverage has been rising.[58] 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.[58] 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.[64] These results have been important in decisions by many countries to start vaccination programs.[65] 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.[66] 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.[67] 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 yet is still recommended due to the existent risk (including oral cancer).[47] 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.[68] 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%).[69] HistoryResearch 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.[70] In December 2014, the FDA approved Gardasil-9, which protects against 9 strains of HPV.[71] Society and cultureUnited StatesThe 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,[72] which has upset some conservative and libertarian groups.[61][73][74] 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,[61][74][75][76] but no evidence exists to suggest that girls who were vaccinated went on to engage in more sexual activity than unvaccinated girls .[77] 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.[78] 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.[78] Furthermore, awareness among teens of HPV is very low meaning that they may catch HPV without knowing what it is or that there is a vaccine for it.[79] 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] JapanIn 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] References1. ^{{cite web | url = http://www.emea.europa.eu/humandocs/Humans/EPAR/silgard/silgard.htm | title = Silgard European Public Assessment Report | publisher = European Medicines Agency | date = September 25, 2009 | access-date = 2009-12-05 | deadurl = yes | archive-url = https://web.archive.org/web/20081225130419/http://www.emea.europa.eu/humandocs/Humans/EPAR/silgard/silgard.htm | archive-date = December 25, 2008 | df = }} 2. ^{{cite web|last=Waknine|first=Yael | name-list-format = vanc |url=http://www.medscape.com/viewarticle/545374|title=International Approvals: Singulair and Gardasil/Silgard|date=October 2, 2006|work=Medscape Today|access-date=2008-12-18|deadurl=no|archive-url=https://web.archive.org/web/20130520232942/http://www.medscape.com/viewarticle/545374|archive-date=May 20, 2013|df=}} 3. ^{{cite news | url = https://www.reuters.com/article/rbssPharmaceuticals%20-%20Generic%20&%20Specialty/idUSN2052127820090820 | title = U.S. health officials back safety of Merck vaccine | work = Reuters | date = August 20, 2009 | access-date = 2009-11-12 | first = Lisa | last = Richwine | name-list-format = vanc | deadurl = no | archive-url = https://web.archive.org/web/20090827011806/http://www.reuters.com/article/rbssPharmaceuticals%20-%20Generic%20%26%20Specialty/idUSN2052127820090820 | archive-date = August 27, 2009 | df = }} 4. ^1 2 {{cite journal | vauthors = Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER | title = Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP) | journal = MMWR. 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| pages = 1444–51 | date = October 2011 | pmid = 21908768 | doi = 10.1093/jnci/djr319 | pmc = 3186781 }} 28. ^{{cite web | author = World Health Organization | title = Summary of the SAGE April 2014 meeting | date = April 2014 | url = http://www.who.int/immunization/sage/meetings/2014/april/report_summary_april_2014/en/ | access-date = 2 June 2015 | deadurl = no | archive-url = https://web.archive.org/web/20150731031733/http://www.who.int/immunization/sage/meetings/2014/april/report_summary_april_2014/en/ | archive-date = 31 July 2015 | df = }} 29. ^{{cite web|url=https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html|title=CDC recommends only two HPV shots for younger adolescents|website=|publisher=Centers for Disease Control and Prevention|access-date=October 7, 2017|deadurl=no|archive-url=https://web.archive.org/web/20170323234605/https://www.cdc.gov/media/releases/2016/p1020-hpv-shots.html|archive-date=March 23, 2017|df=}} 30. ^{{cite journal | vauthors = Giuliano AR, Palefsky JM, Goldstone S, Moreira ED, Penny ME, Aranda C, Vardas E, Moi H, Jessen H, Hillman R, Chang YH, Ferris D, Rouleau D, Bryan J, Marshall JB, Vuocolo S, Barr E, Radley D, Haupt RM, Guris D | title = Efficacy of quadrivalent HPV vaccine against HPV Infection and disease in males | journal = The New England Journal of Medicine | volume = 364 | issue = 5 | pages = 401–11 | date = February 2011 | pmid = 21288094 | pmc = 3495065 | doi = 10.1056/NEJMoa0909537 | laysummary = http://www.aidsmap.com/Gardasil-safe-and-effective-in-young-men/page/1635174/ | displayauthors = 8 }} 31. ^{{cite web | url = http://info.cancerresearchuk.org/news/archive/cancernews/2007-02-23-gay-men-seeking-hpv-vaccine | title = Gay men seeking HPV vaccine | work = Cancer Research UK | date = 23 February 2007 | access-date = 2009-11-12 | deadurl = yes | archive-url = https://web.archive.org/web/20100324231910/http://info.cancerresearchuk.org/news/archive/cancernews/2007-02-23-gay-men-seeking-hpv-vaccine | 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url=https://www.cdc.gov/hpv/downloads/9vhpv-fda.pdf | title=FDA licensure of 9-valent human papillomavirus vaccine to include males aged 16–26 years | publisher=U.S. Centers for Disease Control and Prevention (CDC) | date=2015-12-14 | access-date=2016-10-10 | deadurl=no | archive-url=https://web.archive.org/web/20170130213511/https://www.cdc.gov/hpv/downloads/9vhpv-fda.pdf | archive-date=2017-01-30 | df= }} 35. ^{{cite web | url=https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv-gardasil-9-hcp-info.pdf | title=Provider Information: Gardasil® 9 VIS | publisher=U.S. Centers for Disease Control and Prevention (CDC) | date=December 2015 | access-date=2016-10-10 | deadurl=no | archive-url=https://web.archive.org/web/20170211153114/https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv-gardasil-9-hcp-info.pdf | archive-date=2017-02-11 | df= }} 36. ^{{cite web | url=http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf | title=Highlights of 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Bernard | work = AIDSmap | date = August 29, 2005 | access-date = 2006-06-08 | deadurl = no | archive-url = https://web.archive.org/web/20060619111758/http://www.aidsmap.com/en/news/44e54c4a-27d9-45fe-8533-a0e7c70499b8.asp | archive-date = June 19, 2006 | df = }} 40. ^1 2 3 {{cite web| url=http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf| title=Gardasil full prescribing information| publisher=Merck & Co.| access-date=2009-11-11| deadurl=no| archive-url=https://www.webcitation.org/66GSUD1h0?url=http://www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf| archive-date=2012-03-18| df=}} 41. ^{{cite web | author = electronic Medicines Compendium | title = Gardasil | date = 9 December 2014 | url = https://www.medicines.org.uk/emc/medicine/19016 | access-date = 2 June 2015 | deadurl = no | archive-url = https://web.archive.org/web/20151024054713/https://www.medicines.org.uk/emc/medicine/19016 | archive-date = 24 October 2015 | df = }} 42. ^{{cite journal| vauthors=Vichnin M, Bonanni P, Klein NP, Garland SM, Block SL, Kjaer SK|display-authors=etal| title=An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015. | journal=Pediatr Infect Dis J | year= 2015 | volume= 34 | issue= 9 | pages= 983–91 | pmid=26107345 | doi=10.1097/INF.0000000000000793 | pmc= |type=Review}} 43. ^Donald G McNeil Jr for the New York Times. March 31, 2014 [https://www.nytimes.com/2014/04/01/health/an-expansion-in-use-of-cancer-vaccine.html Expansion in Use Of Cancer Vaccine] {{webarchive|url=https://web.archive.org/web/20160206142351/http://www.nytimes.com/2014/04/01/health/an-expansion-in-use-of-cancer-vaccine.html |date=2016-02-06 }} 44. ^1 2 {{cite web|url=https://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-young-women.htm|title=HPV Vaccine Information For Young Women|publisher=Centers for Disease Control and Prevention (CDC)|access-date=2009-06-14|deadurl=no|archive-url=https://web.archive.org/web/20090628203926/http://www.cdc.gov/std/hpv/STDFact-HPV-vaccine-young-women.htm|archive-date=2009-06-28|df=}} 45. ^{{cite news| url = http://abcnews.go.com/Health/PainManagement/story?id=4082103| title = Cervical cancer shots are gaining reputation as painful| author = Mike Stobbe| work = ABC News| agency = Associated Press| date = January 3, 2008}} 46. ^{{cite news| url = http://www.washingtontimes.com/news/2008/jul/10/merck-fda-expand-gardasil-warnings| title = Merck, FDA expand Gardasil warnings| author = Amy Fagan| work = The Washington Times| date = 10 July 2008| deadurl = no| archive-url = https://web.archive.org/web/20080717080917/http://www.washingtontimes.com/news/2008/jul/10/merck-fda-expand-gardasil-warnings/| archive-date = 17 July 2008| df = }} 47. ^1 2 {{cite news |first=Elisabeth |last=Rosenthal | name-list-format = vanc |work=The New York Times |date=2008-08-19 |url=https://www.nytimes.com/2008/08/20/health/policy/20vaccine.html |title=Drug Makers' Push Leads to Cancer Vaccines' Fast Rise |access-date=2008-08-20 |deadurl=no |archive-url=https://web.archive.org/web/20090409005806/http://www.nytimes.com/2008/08/20/health/policy/20vaccine.html |archive-date=2009-04-09 |df= }} 48. ^1 {{cite web| url = https://www.cdc.gov/vaccinesafety/Vaccines/HPV/HPVArchived.html| title = Information from FDA and CDC on Gardasil and its Safety (Archived)| 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Yes | journal = Canadian Family Physician | volume = 54 | issue = 3 | pages = 342, 344 | date = March 2008 | pmid = 18337521 | pmc = 2278341 }} 68. ^{{cite journal | vauthors = Rothman SM, Rothman DJ | title = Marketing HPV vaccine: implications for adolescent health and medical professionalism | journal = JAMA | volume = 302 | issue = 7 | pages = 781–6 | date = August 2009 | pmid = 19690311 | doi = 10.1001/jama.2009.1179 | df = }} 69. ^{{cite web|author=Haelle, Tara|authorlink=Tara Haelle|url=https://www.forbes.com/sites/tarahaelle/2016/02/23/hpv-infection-rates-plummet-in-young-women-due-to-vaccine/#3b6a130d5c4d|title=HPV Infection Rates Plummet In Young Women Due To Vaccine|work=Forbes|date=February 23, 2016|access-date=February 23, 2016|deadurl=no|archive-url=https://web.archive.org/web/20160226093032/http://www.forbes.com/sites/tarahaelle/2016/02/23/hpv-infection-rates-plummet-in-young-women-due-to-vaccine/#3b6a130d5c4d|archive-date=February 26, 2016|df=}} 70. ^{{cite journal | vauthors = McNeil C | title = Who invented the VLP cervical cancer vaccines? | journal = Journal of the National Cancer Institute | volume = 98 | issue = 7 | pages = 433 | date = April 2006 | pmid = 16595773 | doi = 10.1093/jnci/djj144 | url = http://jnci.oxfordjournals.org/content/98/7/433.full | archive-url = https://web.archive.org/web/20140226001813/http://jnci.oxfordjournals.org/content/98/7/433.full | df = | deadurl = no | archive-date = 2014-02-26 }} 71. ^{{cite web|url=http://www.mrknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-hpv-vaccine-gardasil9-prevent-cancers-an|title=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|author=|date=|website=www.mrknewsroom.com|deadurl=no|archive-url=https://web.archive.org/web/20171027084211/http://www.mrknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-hpv-vaccine-gardasil9-prevent-cancers-an|archive-date=2017-10-27|df=}} 72. ^{{cite news|url=https://www.nytimes.com/2007/02/21/business/21merck.html|title=Merck to halt lobbying for vaccine for girls|first1=Andrew|last1=Pollack|first2=Stephanie|last2=Saul | name-list-format = vanc |date=21 February 2007|access-date=4 July 2018|work=New York Times}} 73. ^{{cite journal|last=Houppert|first=Karen | name-list-format = vanc |url=http://www.thenation.com/doc/20070326/houppert/print|title=Who's Afraid of Gardasil?|journal=The Nation|date=March 26, 2007|access-date=2009-11-11}} 74. ^1 {{cite news|url=https://www.independent.co.uk/news/business/news/moral-majority-take-on-gsk-and-merck-over-cancer-drugs-481844.html|title=Moral majority take on GSK and Merck over cancer drugs|author=Danny Fortson|work=The Independent|date=11 June 2006|access-date=2006-06-12|deadurl=no|archive-url=http://archive.wikiwix.com/cache/20060614122733/https://www.independent.co.uk/news/business/news/moral-majority-take-on-gsk-and-merck-over-cancer-drugs-481844.html|archive-date=14 June 2006|df=}} 75. ^{{cite news |url=http://www.speroforum.com/site/article.asp?idCategory=33&idsub=128&id=5444&t=GARDASIL+vaccine+touted+in+Michigan |title=Gardasil vaccine touted in Michigan |last=Barillas |first=Martin | name-list-format = vanc |work=Spero News |date=2006-09-14 |access-date=2007-01-26 |deadurl=no |archive-url=https://web.archive.org/web/20061114194535/http://www.speroforum.com/site/article.asp?idCategory=33&idsub=128&id=5444&t=GARDASIL+vaccine+touted+in+Michigan |archive-date=2006-11-14 |df= }} 76. ^{{cite web|url=http://downloads.frc.org/EF/EF07H25.pdf|title=Gardasil: What Parents should know about the new HPV vaccine|last=Gaul|first=Moira | name-list-format = vanc |publisher=Family Research Council|year=2007|access-date=2011-09-13}} 77. ^{{cite journal | vauthors = Bednarczyk RA, Davis R, Ault K, Orenstein W, Omer SB | title = Sexual activity-related outcomes after human papillomavirus vaccination of 11- to 12-year-olds | journal = Pediatrics | volume = 130 | issue = 5 | pages = 798–805 | date = November 2012 | pmid = 23071201 | doi = 10.1542/peds.2012-1516 }} 78. ^1 {{Cite journal|last=McMahon|first=Wendy|date=2009|title=Should the administration of the HPV vaccine Gardasil be mandated for young girls entering the sixth grade?|url=https://search-proquest-com.proxy1.lib.uwo.ca/docview/305172502?pq-origsite=summon&accountid=15115|journal=ProQuest|volume=|pages=|via=}} 79. ^{{cite journal | vauthors = Samkange-Zeeb FN, Spallek L, Zeeb H | title = Awareness and knowledge of sexually transmitted diseases (STDs) among school-going adolescents in Europe: a systematic review of published literature | journal = BMC Public Health | volume = 11 | pages = 727 | date = September 2011 | pmid = 21943100 | pmc = 3189891 | doi = 10.1186/1471-2458-11-727 }} 80. ^{{cite news|title=In Republican Race, a Heated Battle Over the HPV Vaccine|url=https://www.nytimes.com/2011/09/14/us/politics/republican-candidates-battle-over-hpv-vaccine.html | first1 = Trip | last1 = Gabriel| first2 = Denise | last2 = Grady | name-list-format = vanc |work=New York Times|date=2011-09-13|access-date=2011-09-14|deadurl=no|archive-url=https://web.archive.org/web/20110914111415/http://www.nytimes.com/2011/09/14/us/politics/republican-candidates-battle-over-hpv-vaccine.html|archive-date=2011-09-14|df=}} 81. ^Japan Times. (16 June 2013). "Cervix vaccine issues trigger health notice {{webarchive|url=https://web.archive.org/web/20131203033434/http://www.japantimes.co.jp/news/2013/06/15/national/cervix-vaccine-issues-trigger-health-notice/ |date=2013-12-03 }}." Accessed 9 July 2013. 82. ^The Asahi Shimbun. (15 June 2013). "Health ministry withdraws recommendation for cervical cancer vaccine {{webarchive |url=https://web.archive.org/web/20130619025016/http://ajw.asahi.com/article/behind_news/social_affairs/AJ201306150057 |date=June 19, 2013 }}." Accessed 9 July 2013. 83. ^1 {{cite journal | vauthors = Hanley SJ, Yoshioka E, Ito Y, Kishi R | title = HPV vaccination crisis in Japan | journal = Lancet | volume = 385 | issue = 9987 | pages = 2571 | date = June 2015 | pmid = 26122153 | doi = 10.1016/S0140-6736(15)61152-7 }} Further reading{{refbegin|32em}}
External links{{portal|Viruses}}
6 : Merck|Papillomavirus|Vaccines|Subunit vaccines|Cancer vaccines|Life sciences industry |
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