HPV vaccine

HPV vaccine

Vaccine description
Target disease	human papillomavirus
Type	Protein subunit
Clinical data
Pregnancy cat.	B(US)
Legal status	℞-only (US)
Routes	injection
Identifiers
ATC code	J07BM01 J07BM02
N(what is this?)  (verify)

The human papilloma virus (HPV) vaccine prevents infection with certain species of human papillomavirus associated with the development of cervical cancer, genital warts, and some less common cancers.^[1][2][3] Two HPV vaccines are currently on the market: Gardasil and Cervarix.^[4]

Both vaccines protect against the two HPV types (HPV-16 and HPV-18) that cause 70% of cervical cancers, and cause most HPV-induced genital and head and neck cancers. Gardasil also protects against the two HPV types (HPV-6 and HPV-11) that cause 90% of genital warts.^[2] In addition, Gardasil has been shown to prevent potential precursors to anal,^[5][6] vulvar,^[7] vaginal,^[7] and penile^[5] and head and neck cancers. HPV vaccines are expected to protect against HPV induced cancers of these areas as well as HPV induced oral cancers.^[8]

Public health officials in Australia, Canada, Europe, and the United States recommend vaccination of young women against HPV to prevent cervical cancer, and to reduce the number of painful and costly treatments for cervical intraepithelial neoplasia, which is caused by HPV.^[9]

Worldwide, HPV is the most common sexually transmitted infection in adults.^[3] For example, more than 80% of American women will have contracted at least one strain of HPV by age fifty.^{[10][11][12][13][14]}

Although most women infected with genital HPV will not have complications from the virus,^[15] worldwide there are an estimated 470,000 new cases of cervical cancer that result in 233,000 deaths per year.^[16] About eighty percent of deaths from cervical cancer occur in poor countries.^[17] In the United States, most of the approximately 11,000 cervical cancers found annually^[18] occur in women who have never had a Pap smear, or not had one in the previous five years. HPV is also the cause of cervical intraepithelial neoplasia (CIN).^[19] CIN is a precursor to cervical cancer, and is painful and costly to treat.^[20] It is not known how many women worldwide are diagnosed with CIN.^[21]

Since the vaccine only covers some high-risk types of HPV, experts still recommend regular Pap smear screening even after vaccination.^[22]

Gardasil has been shown to also be effective in preventing genital warts in males, and use for men and boys was approved by the U.S. Food and Drug Administration (FDA) on October 16, 2009.^[5][23][24] On October 25, 2011 the Advisory Committee on Immunization Practices of CDC made the vaccination recommendation for males 13 to 21 years who have not been vaccinated previously or who have not completed the three-dose series.^[25]

Efficacy

Both Gardasil^[22] and Cervarix^[26] have been shown to prevent cervical dysplasia from the HPV strains that they target, that is, types 16, 18, 6, and 11 for Gardasil and types 16 and 18 for Cervarix. This effect has lasted 4 years after vaccination for Gardasil^[22] and more than 6 years for Cervarix.^[27][28][29] As of September 2010^[update], it is thought that booster vaccines will not be necessary.^[30]

The vaccines also offer some protection against a few high-risk HPV types that are closely related to HPVs 16 and 18. Cervarix has been shown to offer some protection against types 45 and 31,^[31] similarly, Gardasil has been shown to offer some protection against type 31, and 9 others.^[32] However, there are other high-risk HPV types that are not affected by the vaccines.^[33]

Safety

Gardasil is a 3-dose (injection) vaccine. As of 1 September 2009 (2009 -09-01)^[update] there have been more than 26 million doses distributed in the United States, and there have been 15,037 Vaccine Adverse Event Reporting System (VAERS) reports following the vaccination.^[34] Ninety-two percent were reports of events considered to be non-serious (e.g., fainting, pain and swelling at the injection site (arm), headache, nausea and fever), and 8 percent were considered to be serious (death, permanent disability, life-threatening illness and hospitalization). There is no proven causal link between the vaccine and serious adverse effects; all reports are related by time only. That is, they are only related because the effect happened some time after the vaccination.^[34]

As of 1 September 2009 (2009 -09-01)^[update], there have been 44 U.S. reports of death among females who have received the vaccine.^[34] None of the 27 confirmed deaths of women and girls who had taken the vaccine were linked to the vaccine.^[34] Guillain-Barré Syndrome (GBS), a rare disorder that causes muscle weakness, has been reported after vaccination with Gardasil. There is no evidence suggesting that Gardasil causes or raises the risk of GBS. Additionally, there have been rare reports of blood clots forming in the heart, lungs and legs.^[34]

As of 5 November 2009 (2009 -11-05)^[update] the CDC continues to recommend Gardasil vaccination for the prevention of four types of HPV.^[34] Merck, the manufacturer of Gardasil, will continue to test women who have received the vaccine to determine the vaccine's efficacy over a lifetime.^{[citation needed]}

History

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.^[35] In 2006, the U.S. Food and Drug Administration (FDA) approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil. According to a Merck press release,^[36] in the second quarter of 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.^[37] Cervarix was approved for use in the U.S. in October 2009.^[38]

Prevalence of genital HPV

United States

See also: HPV: Prevalence of Genital HPV

According to the Centers for Disease Control and Prevention, by the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV.^[39] Both men and women can be carriers of HPV.^[18] HPV is the most common sexually transmitted infection in the US.^[39] A large percentage of the American population is infected with genital HPV^[40] because HPV is highly communicable. As a result, American public health experts recommend widespread HPV vaccination.^[41]

At a given time, the overall prevalence of high-risk (cancer causing) HPV types was 15% of female participants; the prevalence of the types covered by the vaccine were 1.5% (HPV-16) and 0.8% (HPV-18). The overall prevalence of low-risk (wart causing) types was 18%, the two types covered by the vaccine were found in 1.3% (HPV-6) and 0.1% (HPV-11) of the population. Overall, the types prevented by the vaccine were found in 3.4% of female participants.^[12]

Only a small percentage of women with high-risk HPV develop cervical cancer.^[42] However, each year between 250,000 and 1 million American women are diagnosed with cervical dysplasia, which is caused by HPV and is a precursor to cervical cancer. Cervical dysplasia is painful and costly to treat.^[20]

About 11,000 American women are diagnosed with cervical cancer every year, and about 4,000 die per year of the disease.^[18] Most cancers occur in those who have not had Pap smears within the previous five years.

Estimated proportion of new cases of cancers attribuatble to HPV in 2002^[43]

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.^[44] Studies have found that human papillomavirus (HPV) infection is responsible for virtually all cases of cervical cancer.^[42][45]

Condoms protect against HPV, but do not completely prevent transmission.^[46][47][48] 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.^[46][47][48]

No data is kept by the U.S. government on genital wart incidence rates.^[49] It is estimated that in the U.S., at any one time about 1% of adults who have had sex have genital warts.^[50] It is estimated that about 20 million people are presently infected with HPV, and there are about six million new cases of HPV every year in the United States.^[50]

Worldwide

Worldwide, cervical cancer is the fifth most deadly cancer in women.^[51] There are an estimated 470,000 new cases of cervical cancer, and 233,000 deaths per year.^[16] Due to the success of Pap smear screening programs, the majority of cervical cancers and deaths occur in less developed parts of the world.^[43]

Vaccination and public health

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.

—American National Cancer Institute, ^[22]

Comments made by Dr. Diane Harper, researcher for the HPV vaccines, were interpreted as indicating that in countries where Pap smear screening is common, it will take vaccination of a large proportion of women in order to further reduce cervical cancer rates.^{[52][53][unreliable source?]}

Current preventive vaccines protect against the two HPV types (16 and 18) that cause about 70% of cervical cancers worldwide.^[54] Because of the distribution of HPV types associated with cervical cancer, the vaccines are likely to be most effective in Asia, Europe and North America.^[54] Some other high risk types cause a larger percentage of cancers in other parts of the world.^[54] Vaccines that protect against more of the types common in cancers would prevent more cancers, and be less subject to regional variation.^[54] For instance, a vaccine against the seven types most common in cervical cancers (16, 18, 45, 31, 33, 52, 58) would prevent an estimated 87% of cervical cancers worldwide.^[54]

Only 41% of women with cervical cancer in the developing world are able to access medical treatment for their illness.^[55] Therefore, prevention of HPV by vaccination may be a more effective way of lowering the disease burden in developing countries than cervical screening. The European Society of Gynecological Oncology sees the developing world as most likely to benefit from HPV vaccination.^[56] However, individuals in many resource-limited nations, Kenya for example, are unable to afford the vaccine.^[57]

Vaccine target populations

Gardasil and Cervarix are preventative vaccines and do not treat HPV infection or cervical cancer. They are recommended for women who are 9 to 25 years old who have not been exposed to 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.

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 Papillomavirus (HPV) vaccines are effective in preventing cervical cancer for women up to 45 years of age.^[58]

In November 2007, Merck presented new data on Gardasil. In an investigational study, Gardasil reduced incidence of HPV types 6, 11, 16 and 18-related persistent infection and disease in women through age 45. The study evaluated women who had not contracted at least one of the HPV types targeted by the vaccine by the end of 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.^[59]

Vaccination during pregnancy

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.^[60] However, the clinical trials had a relatively small sample size. Currently the vaccine is not recommended for pregnant women.^[61][60] The long-term effects of the vaccine on fertility are not known, but no effects are anticipated.

Vaccination of males

In the UK, HPV vaccines are licensed for boys aged 9–15.^[62] On 9 September 2009, an advisory panel recommended that the U.S. Food and Drug Administration (FDA) licence Gardasil in the United States for boys and men ages 9–26 for the prevention of genital warts^[63] The vaccine has been FDA approved for use in males age 9 to 26 for prevention of genital warts.^[23] and anal cancer.^[6]

In males, Gardasil may reduce their risk of genital warts and precancerous lesions caused by HPV.^[5] This reduction in precancerous lesions might be predicted to reduce the rates of penile and anal cancer in men.^[5] 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.^[64]

From a public health point of view, vaccinating men as well as women decreases the virus pool within the population, but is only cost-effective if the uptake in the female population is extremely low.^[65] In the United States, the cost per quality-adjusted life year is greater than $100,000 for vaccinating the male population, compared to the less than $50,000 for vaccinating the female population.^[65] This assumes a 75% vaccination rate.

Gardasil is in particular demand among gay men, who are at higher risk for genital warts, penile cancer, and anal cancer.^[66]

As with females, the vaccine should be administered before infection with the HPV types covered by the vaccine occurs. Vaccination before adolescence therefore makes it more likely that the recipient has not been exposed to HPV.

Mechanism of action

The latest generation of preventive HPV vaccines is based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The vaccines target the two high-risk HPVs, types 16 and 18 that cause the most cervical cancers. Together, these two HPV types currently cause about 70 percent of all cervical cancer.^[54] Gardasil also targets HPV types 6 and 11, which together currently cause about 90 percent of all cases of genital warts.^[42]

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.^[67]

Research directions

There are high-risk HPV types are not affected by the vaccines.^[33] Ongoing research is focused on the development of HPV vaccines that will offer protection against a broader range of HPV types.^[68]

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.

Therapeutic HPV vaccines

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.^[69]

Vaccine implementation

Main article: Vaccination policy

In developed countries, the widespread use of cervical "Pap smear" screening programs has reduced the incidence of invasive cervical cancer by 50% or more. Current preventive vaccines reduce, but do not eliminate the chance of getting cervical cancer. Therefore, experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.^[70]

Australia

Commencing in 2007 The Australian federal government began funding a voluntary program to make the Gardasil vaccine available free of charge to women aged 12–26 for a period of two years, with an ongoing vaccination program for 12- and 13-year-olds as part of the pre-existing high school vaccination program.^[71][72]

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 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- and 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.^[73][74]

Canada

Canada has approved use of Gardasil.^[75] 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,^[76] free vaccinations to protect women against HPV were slated to begin in September 2007 and will be offered to girls ages 11–14. Similar vaccination programs are being planned in British Columbia and Quebec.^[77][78][79] The cost for the 3 required shots is reported to be $475.00 .

France

On July 17, 2007, France issued a directive^[80] 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).

Germany and Italy

On March 26, 2007, early approval for Gardasil vaccinations was granted in both Germany and Italy.^[81]

Greece

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.^[82][83]

Kenya

Both Cervarix and Gardasil are approved for use within Kenya by the Pharmacy and Poison's Board. However, at a cost of 20,000 Kenyan shillings, which is more than the average annual income for a family, the director of health promotion in the Ministry of Health, Nicholas Muraguri, states that many Kenyans are unable to afford the vaccine.^[57]

New Zealand

The publicly-funded New Zealand HPV Immunisation Programme began on 1 September 2008. Gardasil is available free for New Zealand girls and young women born on or after 1 January 1990 through general practices, some family planning clinics and participating schools. HPV immunization is part of the regular immunization schedule for girls in year 8 at school (or age 12 if not delivered through a school-based programme). There is also a catch-up programme for older girls. Girls born in 1990 and 1991 have until 31 December 2011 to start the programme for free. Girls born from 1992 onwards have until their 20th birthday to start the programmme for free. Over 82,000 New Zealand girls and young women have chosen to get the HPV immunisation in the programme's first year.^[84]

Norway

In Norway, starting from the fall of 2009, HPV vaccination was introduced into the national immunisation programme, for girls aged 12–13. In March 2010, 57% of all girls born in 1997 had received the first dose of the vaccine.^[85]

Romania

In November 2008, Romanian authorities launched a campaign to vaccinate 110,000 girls aged 10 and 11. The Ministry of Health acquired 330,000 vaccine doses for 23 million euros. By an order of the Ministry, the girls' parents must approve or reject the vaccination in writing, and must "fully assume the consequences for their children" if they reject the vaccination.^[86]

South Korea

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.^[87] Approval for use in boys was based on safety and immunogenicity but not efficacy.

Sweden

In Sweden, starting January 1, 2010, girls born in the year 1999 or later and in the ages 10 to 12 can receive a free HPV vaccine.^[88]

United Kingdom

In the UK the vaccine is licensed for girls aged 9 to 15 and for women aged 16 to 26.^[62]

HPV vaccination with Cervarix was introduced into the national immunisation programme in September 2008, for girls aged 12–13 across the UK. A two-year catch up campaign started in Autumn 2009 to vaccinate all girls up to 18 years of age. Catch up vaccination will be offered to:

• 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. Women over the age of 18 are not included in the programme as it would not be cost effective in preventing cervical cancer.

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.^[89]

United States

The cost of HPV vaccine for females under 18 who are uninsured is covered under the federal Vaccines for Children Program.

As of late 2007^[update], about one quarter of US females age 13–17 years had received at least one of the three HPV shots.^[90]

According to the US Centers for Disease Control and Prevention (CDC), getting as many girls vaccinated as early and as quickly as possible will reduce the cases of cervical cancer among middle-aged women in 30 to 40 years and reduce the transmission of this highly communicable infection. Barriers include the limited understanding by many people that HPV causes cervical cancer, the difficulty of getting pre-teens and teens into the doctor's office to get a shot, and the high cost of the vaccine ($120/dose, $360 total for the three required doses, plus the cost of doctor visits).^[1][91]

A survey was conducted in 2009 aiming to gather more information about knowledge and adoption of the HPV vaccine. Thirty percent of 13- to 17-year-olds and 9% of 18- to 26-year-olds out of the total 1,011 young women who were surveyed reported receipt of at least one HPV injection. Knowledge about HPV varied; however, 5% or fewer subjects believed that the HPV vaccine precluded the need for regular cervical cancer screening or safe-sex practices. Few girls and young women believe that the HPV vaccine is protective beyond the true impact of the vaccine. Despite moderate uptake, many females at risk of acquiring HPV have not yet received the vaccine. ^[92]

Legislation

Shortly after the first HPV vaccine was approved, bills to include the vaccine among those that are mandatory for school attendance were introduced in many states.^[93] Only two such bills passed (in Virginia and Washington DC) during the first four years after vaccine introduction.^[93] Mandates have been effective at increasing uptake of other vaccines, such as mumps, measles, rubella, and hepatitis B (which is also sexually transmitted).^[91] However most such efforts developed for five or more years after vaccine release, while financing and supply were arranged, further safety data was gathered, and education efforts increased understanding, before mandates were considered.^[93]

Other measures that have been considered include requiring insurers to cover HPV vaccination, and funding HPV vaccines for those without insurance.

Opt-out policies

Almost all pieces of legislation currently pending in the states that would make the vaccine mandatory for school entrance have an "opt-out" policy.^[94]

State-by-State

The National Conference of State Legislatures periodically issues summaries of HPV vaccine related legislation.^[94]

Other states are also preparing bills to handle issuing the HPV Vaccine.^[94]

State	Proposal	Status	Opt Out Policy
Alaska	Voluntary vaccination program	Passed	Not Applicable
District of Columbia	Bill would require girls to be vaccinated before they turn 13 to attend school.	Passed	Yes
Nevada	Bill would require health insurance companies to cover the cost of the vaccine	Passed into law	Not Applicable
New Hampshire	Voluntary program provides vaccine free of charge to girls between the ages of eleven and eighteen.	Passed and presently in effect.	Yes
Texas	Governor issued executive order requiring that girls entering the sixth grade be vaccinated.	Texas legislature overrode executive order and barred mandatory vaccination until at least 2011.	Yes
Virginia	Bill requires girls entering the sixth grade to be vaccinated.	Passed the legislature. Goes into effect Oct. 1, 2008; to be implemented in fall of 2009.	Yes

Source: National Conference of State Legislatures, state legislatures

Immigrants

Between July 2008 and December 2009, proof of the first of three doses of HPV Gardasil vaccine was required for women ages 11–26 intending to legally enter the United States. This requirement stirred controversy because of the cost of the vaccine, and because all the other vaccines so required prevent diseases which are spread by respiratory route and considered highly contagious.^[95] The Centers for Disease Control and Prevention repealed all HPV vaccination directives for immigrants effective December 14, 2009.^[96]

Opposition in the United States

See also: Vaccine controversy

Health insurance companies

There has been significant opposition from health insurance companies to covering the cost of the vaccine ($360).^[97][98][99]

Religious right and conservative groups

Several 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. They also say that it will lead to early sexual activity, giving a false sense of immunity to sexually transmitted disease. (See Peltzman effect) 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.^{[100][101][102][103]}

Many organizations^{[who?][quantify]} disagree with the argument that the vaccine increases 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."^[104]

References

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External links

Information about the HPV and vaccination

• Information about the cervical cancer vaccine or HPV vaccine from Cancer Council Australia
• HPV MedlinePlus
• Human Papillomavirus (HPV) Centers for Disease Control and Prevention (CDC)
• "Human Papillomavirus (HPV) Vaccines", National Cancer Institute Fact Sheet, US National Institutes of Health, October 22, 2009.

Major media coverage

• Nancy Gibbs (June 21, 2006). "Defusing the War Over the "Promiscuity" Vaccine". Time. http://www.time.com/time/nation/article/0,8599,1206813,00.html. 
• Rob Stein (November 7, 2006). "Vaccine for Girls Raises Thorny Issues". The Washington Post. http://www.washingtonpost.com/wp-dyn/content/article/2006/11/03/AR2006110301966.html. 

Organizations in favor of vaccination

• Harris, Gardiner (30 June 2006). "Panel Unanimously Recommends Cervical Cancer Vaccine for Girls 11 and Up". The New York Times. http://www.nytimes.com/2006/06/30/health/30vaccine.html. 

Organizations opposed to vaccination

• HPV, Vaccines, and Gender Policy Considerations by Abby Lippman, Carolyn Shimmin, Ryan Melynk, Madeline Boscoe for the Canadian Women's Health Network. 2007.
• Vaccination Bill Mutates by Sigrid Fry-Revere