HPV vaccine

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Human papillomavirus (HPV) vaccine is a vaccine that targets certain sexually transmitted strains of human papillomavirus associated with the development of cervical cancer and genital warts.[1] Two HPV vaccines are currently on the market: Gardasil and Cervarix.[2]

Of the more than 100 known HPV types, 37 are known to be transmitted through sexual contact. Infection with sexually transmitted HPVs is very common in adult populations worldwide. According to the Journal of the American Medical Association and the American Social Health Association, by the age of 50 more than 80% of American women will have contracted at least one strain of HPV.[3][4][5] Most people who contract the virus will not develop cervical cancer; however, each year between 250,000 and 1 million American women are diagnosed with cervical dysplasia, which is caused by HPV and is a potential precursor to cervical cancer.[6] Cervical dysplasia may require treatment. In addition, 80% of deaths from cervical cancer occur in poor countries.[7]

For these reasons, some public health officials recommend widespread vaccination against HPV.[8]

Contents

In work that was initiated in the mid 1980s, 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 [9]. In 2006, the U.S. Food and Drug Administration approved the first preventive HPV vaccine, marketed by Merck & Co. under the tradename Gardasil. According to Merck press release [10], in the second quarter 2007, it had been approved in 80 countries, many under fast-track or expedited review. Early in 2007, GlaxoSmithKline filed for approval in the United States for a similar preventive HPV vaccine, known as Cervarix. In June 2007 this vaccine was licenced in Australia, and it was approved in the European Union in September 2007.[11]

In addition to preventive vaccines, such as Gardasil and Cervarix, laboratory research and several human clinical trials are focused on the development of therapeutic HPV vaccines. In general these vaccines focus on the main HPV oncogenes, E6 and E7. Since expression of E6 and E7 is required for promoting the growth of cervical cancer cells (and cells within warts), it is hoped that immune responses against the two oncogenes might eradicate established tumors.[12]

One such candidate, HspE7, is being developed by San Diego-based Nventa Biopharmaceuticals. HspE7 is derived from a fusion platform that uses recombinant DNA technology to covalently fuse heat shock proteins (Hsps) to target antigens, thereby stimulating cellular immune system responses to specific diseases. Nventa is developing HspE7 in combination with the Toll-like receptor 3 (TLR3) agonist adjuvant Poly ICLC for multiple HPV-related diseases, including Cervical Intraepithelial Neoplasia (also knows as cervical dysplasia or CIN), Genital Warts, Cervical Cancer, and head and neck cancers. HspE7 has completed a Phase 1b study assessing its safety and tolerability in 17 patients with CIN,[13] and the company is planning Phase 2 clinical study for HspE7 in patients with high grade cervical dysplasia (CIN 2/3).

See also: Prevalence of Genital HPV

HPV is highly communicable. A large percentage of the American population is infected with genital HPV.[14] Because of the infection rate, some American public health experts recommend mandatory HPV vaccination.[15]

Each year, between 250,000 and 1 million American women are diagnosed with cervical dysplasia, which is caused by HPV and is a potential precursor to cervical cancer.[16] About 11,000 American women are diagnosed with cervical cancer every year, and about 3,700 die per year of the disease.[17] Both men and women can be carriers of HPV.

There are 19 "high-risk" HPV types that can lead to the development of cervical cancer or other genital/anal cancers; some forms of HPV, particularly type 16, have been found to be associated with a form of throat cancer.[18] Most scientific studies have found that human papillomavirus (HPV) infection is responsible for virtually all cases of cervical cancer.[19][20] Only a small percentage of women with HPV develop cervical cancer.[20]

Condoms protect against HPV, but do not completely prevent transmission.[21][22][23] College freshmen women who used condoms consistently had a 37.8% per patient-year incidence of genital HPV, compared to an incidence of 89.3% among those who did not.[24][25][26]

Worldwide, cervical cancer is the fifth most deadly cancer in women.[27]

Gardasil and Cervarix are preventative (rather than therapeutic) vaccines, recommended for women who are 9 to 25 years old and have not contracted HPV. However, since it is unlikely that a woman will have already contracted all four viruses, and because HPV is primarily sexually transmitted, the U.S. Centers for Disease Control and Prevention has recommended vaccination for women up to 26 years of age.

Although HPV types 6 and 11 do not cause cervical cancer, they can cause genital warts. "Warts cause considerable discomfort and psycho-social trauma, so this makes the vaccine more attractive and also provides a reason other than altruism for men to be immunized," explains John Schiller of the National Cancer Institute.[28] From a public health point of view, vaccinating men as well as women might be important if it decreased the virus pool within the population. HPV also causes anal and penile cancer. In the UK the vaccine is licensed for girls and boys aged 9 to 15 and for women aged 16 to 26. Thus, the vaccine has to be administered to adult men "off license".[29]

When Gardasil was first introduced, it was recommended as a prevention for cervical cancer for women that were 25 years old or younger. New evidence suggests that all Human Papilloma Virus (HPV) vaccines are effective in preventing cervical cancer for women up to 45 years of age.[30]

In November 2007, Merck presented new data on Gardasil. This data indicated that in an investigational study, their HPV vaccine reduced incidence of HPV 6, 11, 16 and 18-related persistent infection and disease in women through age 45. The study evaluated women who were free of infection from at least one vaccine HPV type at the beginning of the study, and who remained free of infection with the relevant HPV type(s) until they completed the three-dose vaccination series. Merck planned to submit this data before the end of 2007 to the U.S. Food and Drug Administration (FDA), and to seek an indication for Gardasil for women through age 45.[31]

In the Gardasil clinical trials, 1,115 pregnant women received the HPV vaccine. Overall, the proportions of pregnancies with an adverse outcome were comparable in subjects who received Gardasil and subjects who received placebo [32]. However, the clinical trials had a relatively small sample size. Currently the vaccine is not recommended for pregnant women.[1] The long term effects of this vaccine on fertility are not known, but no effects are anticipated.

The latest generation of preventive HPV vaccines are based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The vaccines target the two most common high-risk HPVs, types 16 and 18. Together, these two HPV types currently cause about 70 percent of all cervical cancer. Gardasil also targets HPV types 6 and 11, which together currently cause about 90 percent of all cases of genital warts.[20]

Gardasil and Cervarix are designed to elicit virus-neutralizing antibody responses that prevent initial infection with the HPV types represented in the vaccine. The vaccines have been shown to offer 100 percent protection against the development of cervical pre-cancers and genital warts caused by the HPV types in the vaccine, with few or no side effects. The protective effects of the vaccine are expected to last a minimum of 4.5 years after the initial vaccination.[33]

While the study period was not long enough for cervical cancer to develop, the prevention of these cervical precancerous lesions (or dysplasias) is believed highly likely to result in the prevention of those cancers.[34]

Although a 2006 study suggests that the vaccines may offer limited protection against a few HPV types that are closely related to HPVs 16 and 18, it is clear that other high-risk HPV types can circumvent the vaccines,[33] and a 2006 study of HPV infection in female university students found that only 14 of 78 infections with high-risk types of HPV were by types 16 and 18, the remaining 64 infections being with 16 other high-risk types of HPV.[citation needed] Ongoing research is focused on the development of HPV vaccines that will offer protection against a broader range of HPV types.[35] There is also substantial research interest in the development of therapeutic vaccines, which seek to elicit immune responses against established HPV infections and HPV-induced cancers.

Main article: vaccination policy

In developed countries, the widespread use of good-quality cervical "Pap smear" screening programs has reduced the incidence of invasive cervical cancer by 50% or more. Current preventive vaccines offer protection against the two HPV types (16 & 18) that currently cause about 70% of cervical cancer cases. Therefore, experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.[36]

HPV-induced cervical cancer remains the fifth most common cancer in women worldwide.[37]

Commencing in 2007 The Australian federal government began funding a voluntary program to make the Gardasil vaccine available free of charge to women aged between 12 and 26 for a period of two years, with an ongoing vaccination program for 12-13 year olds as part of the pre-existing high school vaccination program.[38][39]

In Australia, the Australian government and the PBS (Pharmaceutical Benefits Scheme) have approved the vaccine for use and in 2007 began a nationwide vaccination program free of charge to schoolgirls in years 7 to 12. These programs are run by local councils with funding and vaccine supplies coming from the government. The subsidization approval process, however, appears to have been heavily influenced by political interference from politicians of all political parties, and by the Prime Minister who publicly advised that it would be approved (before approval). In addition, women between 18 and 26 years of age at the time of the first dose may receive the vaccine for free upon request from their general practitioner. After June 2009, the program will be scaled down to 12–13 year old girls only. Australia also approved Gardasil for boys 9–15 years old, but Australia is not providing government funding for vaccinating boys.[40][41]

Canada has approved use of Gardasil[42]. Initiating and funding free vaccination programs has been left to individual Province/Territory Governments. In the provinces of Ontario, Prince Edward Island, Newfoundland and Nova Scotia[43], free vaccinations to protect women against HPV are slated to begin in September 2007 and will be offered to girls 11-14 in age. Similar vaccination programs are also being planned in British Columbia and Quebec.[44][45][46]

On February 12, 2007, Greece made HPV vaccination mandatory for girls entering gymnasion (7th grade). All vaccines including hepatitis B are mandatory and are supplied free to everyone in Greece with parents being allowed to opt out of vaccinating their kids. Cervarix and Gardasil are supplied free to all girls and women between the ages of 12 and 26.[47][48].

On July 17, 2007, France issued a directive[49] authorizing state-aided voluntary vaccination for girls aged 14–23 years who have not yet become sexually active, or have been sexually active for less than a year. The state refunds 65% of the cost, based on a program of 3 vaccinations at €135 (slightly less than $200) per shot, meaning that the patient covers €141.75 (slightly more than $200).

On March 26, 2007, early approval was granted in both Germany and Italy.[50]

From September 2008, Gardasil will be available for New Zealand girls and young women up to the age of 18. From 2009, the HPV immunization program will be part of the regular immunization schedule for 12 year old girls.

On July 27, 2007, South Korean government approved Gardasil for use in girls and women aged 9 to 26 and boys aged 9 to 15.[51] Approval for use in boys was based on safety and immunogenicity but not efficacy.

HPV vaccination will be introduced into the national immunisation programme in September 2008, for girls aged 12-13 across the UK. Then, starting in autumn 2009, a two year catch up campaign will vaccinate all girls up to 18 years of age. This catch up campaign will offer to vaccinate:

  • girls aged between 16 and 18 from autumn 2009, and
  • girls aged between 15 and 17 from autumn 2010.

By the end of the catch up campaign, all girls under 18 will have been offered the HPV vaccine.

When the HPV vaccination programme begins in 2008, women over the age of 18 will not be vaccinated as it would not be cost effective in preventing cervical cancer. This is because as soon as a woman becomes sexually active, she is at risk of infection with the virus.

It will be many years before the vaccination programme has an effect upon cervical cancer incidence so women are advised to continue accepting their invitations for cervical screening.[52]

Almost all pieces of legislation currently pending in the states that would make the vaccine mandatory for school entrance have an "opt-out" policy.[53]

There has been significant opposition from health insurance companies to covering the cost of the vaccine ($360).[54][55][56]

Other states are also preparing bills to handle issuing the HPV Vaccine.[57]

State Proposal Status Opt Out Policy
Alaska Voluntary vaccination program Passed N/A
California Bill would have required girls entering the sixth grade to be vaccinated. Withdrawn for further consideration. Yes
Colorado Bill would require 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out. Pending Yes
Connecticut Bill would require girls receive a first dose of the vaccine before entering the sixth grade. Allows parents to opt their daughters out on medical or religious grounds. Pending Yes
District of Columbia Bill would require girls to be vaccinated before they turn 13 to attend school. Allows parents to opt their daughters out. Pending Yes
Florida Bill would have required 11- and 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out. Died in committee Yes
Georgia Bill would require girls entering the sixth grade to be vaccinated unless parents can't afford the vaccine or object to it on medical or religious grounds. Died in Committee Yes
Illinois Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out. Pending Yes
Kansas Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds. Pending Yes
Kentucky Bill would require girls entering middle school to be vaccinated. Allows parents to opt their daughters out. Passed House, to Senate Yes
Maryland Bill would have required girls entering the sixth grade to be vaccinated. Withdrawn Yes
Massachusetts Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on religious grounds. Pending Yes
Michigan Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out. Pending. Yes
Missouri Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds. Pending Yes
Minnesota Bill would require 12-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out. Pending Yes
Mississippi Bill would have required girls entering the sixth grade to be vaccinated. Died. Sponsor planning to re-introduce it with an opt-out clause. No
Nevada Bill would require health insurance companies to cover the cost of the vaccine Passed into law N/A
New Hampshire Voluntary program provides vaccine free of charge to girls between the ages of eleven and eighteen. Passed and presently in effect. Yes
New Jersey Bill would require girls in grades seven through 12 to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds. Pending Yes
New Mexico Bill would require nine- to 14-year-old girls to be vaccinated to attend school. Allows parents to opt their daughters out. Passed legislature. Vetoed by governor. Yes
Ohio Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out. Pending Yes
Oklahoma Bill would require girls entering the sixth grade to be vaccinated. Pending Yes
South Carolina Bill would require girls entering the seventh grade or 11 years of age to be vaccinated. Allows parents to opt their daughters out on medical or religious grounds. Pending Yes
Texas Governor issued executive order requiring that girls entering the sixth grade be vaccinated. Allows parents to opt their daughters out. Texas legislature overrode executive order and barred mandatory vaccination until at least 2011. Yes
Vermont Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical, moral or religious grounds. Pending Yes
Virginia Bill requires girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out. Passed the legislature. Goes into effect Oct. 1, 2008; to be implemented in fall of 2009. Yes
West Virginia Bill would require girls entering the sixth grade to be vaccinated. Allows parents to opt their daughters out on medical grounds. Died n/a

Source: National Conference of State Legislatures, state legislatures

Main article: Vaccine controversy

According to the FDA and CDC, the vaccine has only minor side effects, such as soreness around the injection area. The FDA and CDC consider the vaccine to be completely safe. It does not contain mercury, thimerosal or live or dead virus, only virus-like particles, which cannot reproduce in the human body.[1] Merck, the manufacturer of Gardasil, will continue to test women who have received the vaccine to determine the vaccine's efficacy over the period of a lifetime.

A group called the National Vaccine Information Center released an article on Feb 22, 2007, about Gardasil. NVIC is a non-governmental, non-profit organization "dedicated to preventing vaccine injuries and deaths through public education." The NVIC does not conduct scientific research, but is highly critical of most vaccinations.[58] The NVIC claims "new analysis of the federal Vaccine Adverse Event Reporting System reports of serious health problems following HPV vaccination (Merck's GARDASIL) during the last six months of 2006." However, reports from the Vaccine Adverse Event Reporting System database are subject to interpretation as explained at the official website: "When evaluating data from VAERS, it is important to note that for any reported event, no cause and effect relationship has been established... VAERS collects data on any adverse event following vaccination, be it coincidental or truly caused by a vaccine." The NVIC interprets the information in VAERS to mean that "two thirds of the 385 adverse incidents are related to Gardasil injections required secondary medical treatment." The NVIC article goes on to say, "event reports to VAERS do not prove causation." However, the NVIC implies a causal relationship between Gardasil and what the FDA believes are unrelated illnesses.[58]

In October 2007, the conservative group Judicial Watch reported they had obtained Vaccine Adverse Event Reporting System (VAERS) reports relating to Gardasil, “bringing the known total to 3,461 adverse reactions including eleven deaths since FDA approval."[59] Similar to other anti-vaccination groups, Judicial Watch chooses to interpret VAERS reports as proof of vaccination injuries. The FDA and CDC considers the HPV vaccine to be safe and effective.

Several other conservative groups in the U.S. have publicly opposed the concept of making HPV vaccination mandatory for pre-adolescent girls, asserting that making the vaccine mandatory is a violation of parental rights. Both the Family Research Council and the group Focus on the Family support widespread (universal) availability of HPV vaccines but oppose mandatory HPV vaccinations for entry to public school.[60][61][62][63]

Many organizations disagree with the assessment that the vaccine would increase sexual activity among teens. Dr. Christine Peterson, director of the University of Virginia's Gynecology Clinic, said "The presence of seat belts in cars doesn't cause people to drive less safely. The presence of a vaccine in a person's body doesn't cause them to engage in risk-taking behavior they would not otherwise engage in." [64] All states offer an "opt-out" policy which allows parents not to vaccinate their girls for religious reasons.

  1. ^ a b c CDC (2006). "STD Facts - HPV Vaccine". Retrieved on 2007-08-22.
  2. ^ Glaxo cervical cancer shot approved in Australia Reuters (2007-05-21) Retrieved on 2007-05-25
  3. ^ Medical News Today
  4. ^ The Journal of the American Medical Association"More American girls and women have HPV than first thought"
  5. ^ American Social Health Association "Genital HPV is the most common STD in America; an estimated 80% of sexually active individuals will contract it at some point in their lives."
  6. ^ Women's Health Channel "Cervical Dysplasia: Overview, Risk Factors"]
  7. ^ Cervical Cancer Action - Funded by the Rockefeller Foundation
  8. ^ [ http://www.jiwh.org/content.cfm?sectionid=167 Jacobs Institute for Women's Health] New Report Examines Laws that Would Mandate HPV Vaccine for Young Women
  9. ^ Who Invented the VLP Cervical Cancer Vaccines? McNeil, C., Journal of the National Cancer Institute, 2006, 98(7): 433.
  10. ^ Merck News Item
  11. ^ "Glaxo prepares to launch Cervarix after EU okay". Retrieved on 18 July 2008.
  12. ^ Vaccination to prevent and treat cervical cancer Hum Pathol. 2004 Aug;35(8):971
  13. ^ "ClinicalTrialsFeeds.org, Safety Study to Test the Safety of HspE7 and Poly-ICLC Given in Patients With Cervical Intraepithelial Neoplasia". Retrieved on 2008-05-05.
  14. ^ "More American Girls And Women Have HPV Than First Thought". Retrieved on 28 May 2008.
  15. ^ New Report Examines Laws that Would Mandate HPV Vaccine for Young Women George Washington University, December 27, 2007
  16. ^ Women's Health Channel "Cervical Dysplasia: Overview, Risk Factors"]
  17. ^ National Cancer Institute SEER fact sheet on cervical cancer accessed 30 Mar 2007.
  18. ^ D'Souza, Gypsyamber (May 10, 2007). "Case–Control Study of Human Papillomavirus and Oropharyngeal Cancer". New England Journal of Medicine 356: 1944–1956. doi:10.1056/NEJMoa065497. 
  19. ^ [1]
  20. ^ a b c Lowy and Schiller (2006 May). "Prophylactic human papillomavirus vaccines". Journal of Clinical Investigation 116 (5). 
  21. ^ New England Journal of Medicine. Condom Use and the Risk of HPV Infection. 2006 Sep 28;355(13):1388–1389.
  22. ^ New England Journal of Medicine. Condom use and the risk of genital human papillomavirus infection in young women. 2006 Jun 22;354(25):2645–54
  23. ^ Sexually Transmitted Diseases. Condom use and other factors affecting penile human papillomavirus detection in men attending a sexually transmitted disease clinic. 2004 Oct;31(10):601–7
  24. ^ New England Journal of Medicine. Condom Use and the Risk of HPV Infection. 2006 Sep 28;355(13):1388–1389.
  25. ^ New England Journal of Medicine. Condom use and the risk of genital human papillomavirus infection in young women. 2006 Jun 22;354(25):2645–54
  26. ^ Sexually Transmitted Diseases. Condom use and other factors affecting penile human papillomavirus detection in men attending a sexually transmitted disease clinic. 2004 Oct;31(10):601–7
  27. ^ World Health Organization (February 2006). "Fact sheet No. 297: Cancer". Retrieved on 2007-12-01.
  28. ^ HPV vaccine moves into late stage trials, Nature Medicine 7, 388 (2001), accessed May 19, 2006
  29. ^ "Gay men seek 'female cancer' jab". BBC (2007-02-23).
  30. ^ "HPV Vaccine Update". Your Cancer Today (2007-12-11).
  31. ^ 05 Nov 2007, New Data Presented on GARDASIL®, Merck's Cervical Cancer Vaccine, in Women Through Age 45, http://www.merck.com/newsroom/press_releases/product/2007_1105.html
  32. ^ Merck Pregnancy Registries - GARDASIL
  33. ^ a b Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trialLancet. 2006 Apr 15;367(9518):1247-55
  34. ^ "FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in Females Caused by Human Papillomavirus". FDA (2006-06-08). Retrieved on 2007-02-04.
  35. ^ "New HPV Vaccine Under Study.". Medical College of Georgia, ScienceDaily (2007-11-20). Retrieved on 2008-03-01.
  36. ^ Cutts FT, Franceschi S, Goldie S et al. (2007). "Human papillomavirus and HPV vaccines: a review". Bull World Health Organ 85 (9): 719–26. doi:10.2471/BLT.06.038414. PMID 18026629. 
  37. ^ "Cancer facts". World Health Organization (February 2006). Retrieved on 2007-04-05.
  38. ^ Australian Government To Fund Cervical Cancer Vaccine Gardasil
  39. ^ "Australian Government Funding Of Gardasil®", Australian Government Department of Health and Ageing (2006-11-28). Retrieved on 2007-12-02. 
  40. ^ Poljak, Vesna; Daley, Gemma (2006-11-29). "Australia to Subsidize Merck Cervical Cancer Vaccine (Update3)", Bloomberg. Retrieved on 2007-01-26. 
  41. ^ The Department of Health and Ageing (2007-08-13). "The National HPV Vaccination Program - Frequently Asked Questions for Young Women". Retrieved on 2007-09-28.
  42. ^ Human Papillomavirus (HPV) Prevention and HPV Vaccine: Questions and Answers
  43. ^ HPV Immunization Launched
  44. ^ "McGuinty Government Launches Life-Saving HPV Immunization Program:", Premier of Ontario (2007-08-02). Retrieved on 2007-12-02. 
  45. ^ "HPV Immunization Launched", Province of Nova Scotia (2007-06-20). Retrieved on 2007-12-02. 
  46. ^ "British Columbia To Launch Program To Provide HPV Vaccine to Sixth-Grade Girls Next Fall if Approved, Official Says", Kaiser Daily Women's Health Policy, Kaiser Family Foundation (2007-08-09). Retrieved on 2007-12-02. 
  47. ^ http://www.fskilkis.gr/index.php?option=com_content&task=view&id=218&Itemid=2 , Φαρμακευτικός Σύλλογος Κιλκίς (Pharmacy Association of Kilkis).
  48. ^ http://www.iatronet.gr/articlespnsr.asp?art_id=4247.
  49. ^ "Gardasil authorised for subsidised vaccination", French govt news release (in French) (2007-12-31). Retrieved on 2007-12-31. 
  50. ^ Fagbire, OJ (2007-03-26). "Gardasil, Merck HPV Vaccine, Gets German And Italian Approval For Girls", Vaccine Rx. Retrieved on 2007-03-27. 
  51. ^ "가다실® 제품 허가 공지" (2007-06-27). Retrieved on 2007-08-06. 
  52. ^ "NHS Cervical Screening Program". Retrieved on 26 June 2008.
  53. ^ HPV Vaccine
  54. ^ HPV Vaccine - Why Your Doctor Doesn't Offer the HPV Vaccine - Gardasil
  55. ^ Public Health & Education | Detroit News Examines Cost of HPV Vaccine Gardasil - Kaisernetwork.org
  56. ^ A question of protection
  57. ^ HPV Vaccine
  58. ^ a b NVIC.com
  59. ^ Judicial Watch Uncovers New FDA Records Detailing Deaths in 1,824 Adverse Reaction Reports Related to HPV Vaccine
  60. ^ Sprigg, Peter (2006-07-15). "Pro-Family, Pro-Vaccine — But Keep It Voluntary". The Washington Post. Retrieved on 2007-02-04.
  61. ^ Coyne, Brendan (2005-11-02). "Cervical Cancer Vaccine Raises 'Promiscuity' Controversy", The New Standard. Retrieved on 2006-08-28. 
  62. ^ Family Research Council: Thursday, February 7, 2008 "IF07B01"
  63. ^ Focus on the Family Position Statement: Human Papillomavirus Vaccines
  64. ^ "Lifesaving Politics." Ms. Magazine. pp 12-13. Spring 2007.

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subunit: Anthrax • DTaP • HPV •• recombinant DNA: HBV •• other: Anthrax • PPV
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