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HPV vaccine

Vaccine description
Target	human papillomavirus
Vaccine type	Protein subunit
Clinical data
Routes of administration	injection
ATC code	J07BM01 (WHO) J07BM02 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
ChemSpider	NA
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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. Two HPV vaccines are currently on the market: Gardasil and Cervarix.

Both vaccines protect against the two HPV types (HPV-16 and HPV-18) that cause 70% of cervical cancers, 80% of anal cancers, 60% of vaginal cancers, and 40% of vulvar cancers. These HPV types also cause most HPV induced oral cancers, and some other rare genital cancers. Gardasil also protects against the two HPV types (HPV-6 and HPV-11) that cause 90% of genital warts.

Both vaccines have been shown to prevent potentially precancerous lesions of the cervix. Gardasil has been shown to prevent potential precursors to anal, vulvar, vaginal, and penile cancers. HPV vaccines are expected to protect against HPV induced cancers of these areas as well as HPV induced oral cancers.

The World Health Organization (WHO), as well as 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 treatments for cervical cancer precursors.

Worldwide, HPV is the most common sexually transmitted infection in adults. For example, more than 80% of American women will have contracted at least one strain of HPV by age fifty.

Although most women infected with genital HPV will not have complications from the virus, worldwide there are an estimated 529,000 new cases of cervical cancer and 275,000 deaths per year. About 85 percent of cancers, and eighty percent of deaths from cervical cancer occur in developing countries. In the United States, most of the approximately 11,000 cervical cancers found annually 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). CIN is a precursor to cervical cancer, and is painful and costly to treat. It is not known how many women worldwide are diagnosed with CIN.

Since the vaccine only covers some high-risk types of HPV, experts still recommend that women get regular Pap smear screening even after vaccination.

HPV vaccination is approved for use in males in many areas. In addition to protecting their partners from cervical cancer, vaccination can protect males against anal cancer, and may prevent other HPV associated cancers. Gardasil can also protect males against genital warts. HPV vaccination has been recommended for males in the United States, where vaccine uptake among women has been low. Vaccination is also recommended in populations at higher risk for HPV associated cancers, such as men who have sex with men and those with compromised immune response.

Medical uses

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.

Males

HPV vaccines are approved for males in several countries, including Australia, South Korea, the United Kingdom, and the United States.

Gardasil has been shown to also be effective in preventing genital warts in males. 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. Soon after that the vaccine has been approved by U.S. Food and Drug Administration (FDA) for use in males aged 9 to 26 for prevention of genital warts and anal cancer.

On October 25, 2011, an advisory panel for the Centers for Disease Control and Prevention (CDC) voted to recommend that the vaccine be given to boys ages 11–12. The panel's recommendation is intended to prevent genital warts and anal cancers in males, and possibly prevent head and neck cancer (though the vaccine's effectiveness against head and neck cancers has not yet been proven.) The Committee also 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.

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

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. 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. This assumes a 75% vaccination rate.

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.

Gardasil is in particular demand among MSMs, who are at higher risk for genital warts, penile cancer, and anal cancer.

Harald zur Hausen's support for vaccinating boys (so that they will be protected and thereby women) was joined by professors Harald Moi and Ole-Erik Iversen in 2011.

Older women

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.

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.

Efficacy

Both Gardasil and Cervarix have been shown to prevent cervical dysplasia from the high-risk HPV types 16 and 18 and some protection against a few closely related high-risk HPV types. However, there are other high-risk HPV types that are not affected by the vaccines. The protection against HPV 16 and 18 has lasted 5 years after vaccination for Gardasil and more than 6 years for Cervarix. It is thought that booster vaccines will not be necessary.

Gardasil also protects against low-risk HPV types 6 and 11, which do not cause cancer, but do cause genital warts.

A recent analysis of data from a clinical trial of Cervarix found that this vaccine is just as effective at protecting women against persistent HPV 16 and 18 infection in the anus as it is at protecting them from these infections in the cervix. Overall, about 30 percent of cervical cancers will not be prevented by these vaccines. Also, in the case of Gardasil, 10 percent of genital warts will not be prevented by the vaccine. Neither vaccine prevents other sexually transmitted diseases, nor do they treat HPV infection or cervical cancer.

HPV types 16, 18 and 45 contribute to 94% of cervical adenocarcinoma (cancers originating in the glandular cells of the cervix). While most cervical cancer arises in the squamous cells, adenocarcinomas make up a sizable minority of cancers. Further, Pap smears are not as effective at detecting adenocarcinomas, so where Pap screening programs are in place, a larger proportion of the remaining cancers are adenocarcinomas. Trials suggest that HPV vaccines may also reduce the incidence of adenocarcinoma.

Contraindications and precautions

While the use of HPV vaccines can help reduce cervical cancer deaths by two thirds around the world, not everyone is eligible for vaccination. There are some patient factors that exclude people from receiving Gardasil or Cervarix. There factors include:

• Patients with history of immediate hypersensitivity to vaccine components. Patients with a hypersensitivity to yeast should not receive Gardasil since yeast is used in its production.

• Patients with moderate or severe acute illnesses. This does not completely exclude patients from vaccination, it just postpones the time of vaccination until the illness has improved.

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

The FDA has classified the HPV vaccine as a pregnancy Category B, meaning there is no apparent harm on the fetus in animal studies. HPV vaccines have not been causally related with adverse pregnancy outcomes or adverse effects on the fetus However, data on vaccination during pregnancy is very limited and vaccination during the pregnancy term should be delayed until more information is available. If a woman is found to be pregnant during the three dose series of vaccination, the series will be postponed until pregnancy has been completed. While there is no indication for intervention for vaccine dosages administered during pregnancy, patients and health-care providers are encouraged to report exposure to vaccines to the appropriate HPV vaccine pregnancy registry.

Safety

HPV vaccines are approved for use in over 100 countries, with more than 100 million doses distributed worldwide. Extensive clinical trial and post-marketing safety surveillance data indicate that both Gardasil and Cervarix are well tolerated and safe.

See Human papillomavirus Vaccines for Australians: information for immunisation providers, National Centre for Immunisation Research and Surveillance Factsheet: March 2013

Gardasil is a 3-dose (injection) vaccine. As of 8 August 2013 there have been more than 111 million doses distributed in the United States, though it is unknown how many have been administered. There have been 390,800 Vaccine Adverse Event Reporting System (VAERS) reports following the vaccination. Ninety-one 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 9 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; VAERS reports include any effects whether coincidental or causal. The CDC states: "When evaluating data from VAERS, it is important to note that for any reported event, no cause-and-effect relationship has been established. VAERS receives reports on all potential associations between vaccines and adverse events."

As of 1 September 2009, there have been 44 U.S. reports of death in females after receiving the vaccine. None of the 27 confirmed deaths of women and girls who had taken the vaccine were linked to the vaccine. 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.

As of 8 August 2013 the CDC continues to recommend Gardasil vaccination for the prevention of four types of HPV. Merck, the manufacturer of Gardasil, has committed to ongoing research assessing the vaccine's safety.

According to the Disease Control and Prevention (CDC) and the FDA, the rate of adverse side effects related to Gardasil immunization in the safety review were consistent with what has been seen in the safety studies carried out before the vaccine was approved and were similar to those seen with other vaccines. However, a higher proportion of syncope (fainting) and venous thrombolic events (blood clots) were seen with Gardasil than are usually seen with other vaccines. The FDA and CDC have reminded health care providers that, to prevent falls and injuries, all vaccine recipients should remain seated or lying down and be closely observed for 15 minutes after vaccination.

Prevalence of genital HPV

United States

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. Both men and women can be carriers of HPV. HPV is the most common sexually transmitted infection in the US. A large percentage of the American population is infected with genital HPV because HPV is highly communicable. As a result, American public health experts recommend widespread HPV vaccination.

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.

Only a small percentage of women with high-risk HPV 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 precursor to cervical cancer. Cervical dysplasia is painful and costly to treat.

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

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. Studies have found that human papillomavirus (HPV) infection is responsible for virtually all cases of cervical cancer.

Condoms protect against HPV, but do not completely prevent transmission. 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.

No data is kept by the U.S. government on genital wart incidence rates. It is estimated that in the U.S., at any one time about 1% of adults who have had sex have genital warts. 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.

According to the CDC, Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with approximately 20 million people currently infected and an estimated 6.2 million additional people who become newly infected every year. More than 100 HPV types have been identified, over 40 of which can infect the genital area. High risk, or oncogenic types, including types 16 and 18, can cause high-grade cervical cell abnormalities that are precursors to cervical cancer and other cancers such as vulvar, vaginal and anal cancers as well as some oropharyngeal cancers. Low risk, or non-oncogenic types, such as HPV 6 or 11, can cause benign or low-grade abnormalities of cervical cells, genital warts, and a disease of the respiratory tract called recurrent respiratory papillomatosis. Most HPV infections are transient and asymptomatic, causing no clinical manifestations.

In August 2012, the Medscape website released a slides presentation about HPV and cancer risk. The following table shows the incidence of HPV associated cancers in the period of 2004-2008 at US.

Worldwide

Worldwide, cervical cancer is the fourth most deadly cancer in women. There were an estimated 529,000 new cases of cervical cancer, and 275,000 deaths in 2008. Due to the success of Pap smear screening programs at reducing cervical cancer in more developed countries, the majority of cervical cancers (85%) and deaths (80%) occur in less developed parts of the world.

Vaccination and public health

The National Cancer Institute states "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."

Current preventive vaccines protect against the two HPV types (16 and 18) that cause about 70% of cervical cancers worldwide. 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. Some other high risk types cause a larger percentage of cancers in other parts of the world. Vaccines that protect against more of the types common in cancers would prevent more cancers, and be less subject to regional variation. 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.

Only 41% of women with cervical cancer in the developing world get medical treatment. 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. However, individuals in many resource-limited nations, Kenya for example, are unable to afford the vaccine.

In more developed countries, populations that do not receive adequate medical care, such as poor or minorities in the United States or parts of Europe also have less access to cervical screening and appropriate treatment, and are similarly more likely to benefit. Comments made by Dr. Diane Harper, a 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. She has also encouraged women to continue pap screening after they are vaccinated and to be aware of potential adverse effects.

Mechanism of action

The HPV vaccines are based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The virus possesses circular double stranded DNA and a viral shell that is composed of 72 capsomeres. Every subunit of the virus is composed of two proteins molecules, L1 and L2. The reason why this virus has the capability to affect the skin and the mucous layers is due to its structure. The primary structures expressed in these areas are E1 and E2, these proteins are responsible for the replication of the virus. E1 is a highly conserved protein in the virus, E1 is in charge of the production of viral copies is also involved in every step of replication process. The second component of this process is E2 ensures that non-specific interaction occur while interacting with E1. As a result of these proteins working together is assures that numerous amounts of copies are made within the host cell. The structure of the virus is critical because this influence the infection affinity of the virus. Knowing the structure of the virus allowed for the development of an efficient vaccine, such Gardasil and Cervarix. The vaccines target the two high-risk HPVs, types 16 and 18 that cause the most cervical cancers. Gardasil's proteins are synthesized by the yeast Saccharomyces cerevisiae. Its protein makeup allows it to target four types of HPV. Gardasil contains inactive L1 proteins from four different HPV strains: 6, 11, 16, and 18. Each vaccine dose contains 225 mcg of aluminum, 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of polysorbate 80, 35 mcg of sodium borate, and water. The combination of ingredients totals 0.5 mL. 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.

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.

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.

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. Researchers Ian Frazer and Jian Zhou at the University of Queensland have been accorded priority under U.S. patent law for the invention of the HPV vaccine's basis, the VLPs. 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, 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. Cervarix was approved for use in the U.S. in October 2009.

Harald zur Hausen, a German researcher who initially suspected and later helped to prove that genital HPV infection can lead to cervical cancer, was awarded half of the $1.4 million Nobel Prize in Medicine for his work. Verification that cervical cancer is caused by an infectious agent led several other groups (see above) to develop vaccines against HPV strains that cause most cases of cervical cancer. The other half of the award went to Françoise Barré-Sinoussi and Luc Montagnier, two French virologists, for their part in the discovery of HIV.

zur Hausen went against current dogma and postulated that oncogenic human papilloma virus (HPV) caused cervical cancer. He realized that HPV-DNA could exist in a non-productive state in the tumours, and should be detectable by specific searches for viral DNA. He and others, notably workers at the Pasteur Institute, found HPV to be a heterogeneous family of viruses. Only some HPV types cause cancer.

Harald zur Hausen pursued his idea of HPV for over 10 years by searching for different HPV types. This research was difficult due to the fact that only parts of the viral DNA were integrated into the host genome. He found novel HPV-DNA in cervix cancer biopsies, and thus discovered the new, tumourigenic HPV16 type in 1983. In 1984, he cloned HPV16 and 18 from patients with cervical cancer. The HPV types 16 and 18 were consistently found in about 70% of cervical cancer biopsies throughout the world.

His observation of HPV oncogenic potential in human malignancy provided impetus within the research community to characterize the natural history of HPV infection, and to develop a better understanding of mechanisms of HPV-induced carcinogenesis.

Research directions

There are high-risk HPV types, that are not affected by the vaccines. Ongoing research is focused on the development of HPV vaccines that will offer protection against a broader range of HPV types. One such method is a vaccine based on the minor capsid protein L2, which is highly conserved across HPV genotypes. Efforts for this have included boosting the immunogenicity of L2 by linking together short amino acid sequences of L2 from different oncogenic HPV types.

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 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. HPV-associated diseases have become an ideal test of antigen-specific immunotherapy due to the expression of viral oncoproteins that provide tumour-specific non-self antigenic targets. The relative accessibility of the lower genital tract makes it easier to study the effect of therapeutic vaccines on the systemic circulation and the target tissue. 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.

Vaccine implementation

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. The European Centre for Disease Prevention and Control (ECDC) has recommended all European teenage girls to be vaccinated however Bulgaria, Cyprus, Czech Republic, Estonia, Finland, Hungary, Lithuania, Malta, Poland, Slovakia and Turkey currently do not have a vaccination programme in place.

Africa

With support from the GAVI Alliance, a number of low-income African countries have begun rollout of the HPV vaccine, with others to follow. In 2013 Ghana, Kenya, Madagascar, Malawi, Niger, Sierra Leone, and the United Republic of Tanzania begin implementation of the vaccine. In 2014, Rwanda will begin nationwide rollout, and demonstration programs will take place in Mozambique and Zimbabwe.

Australia

In April 2007, Australia became the first country to introduce a government funded National Human Papillomavirus (HPV) Vaccination Program to protect young women against HPV infections that can lead to cancers and disease. The National HPV Vaccination Program is listed on the National Immunisation Program (NIP) Schedule and funded under the Immunise Australia Program. The Immunise Australia Program is a joint Australian, State and Territory Government initiative to increase immunisation rates for vaccine preventable diseases.

The National HPV Vaccination Program for females was made up of two components: an ongoing school-based program for 12-13-year-old girls; and a time-limited catch-up program (females aged 14 – 26 years) delivered through schools, general practices and community immunisation services, which ceased on 31 December 2009.

During 2007-2009, an estimated 83% of females aged 12-17 years received at least one dose of HPV vaccine and 70% completed the 3-dose HPV vaccination course. Latest HPV coverage data on the Immunise Australia website show that by 15 years of age, over 70% of Australian females have received all three doses. This has remained steady since 2009.

Since the National HPV Vaccination Program commenced in 2007, there has been a reduction in HPV-related infections in young women. A study published in The Journal of Infectious Disease in October 2012 found the prevalence of vaccine preventable HPV types (6, 11, 16 and 18) in Papanicolaou test results of women aged 18-24 years has significantly decreased from 28.7% to 6.7% four years after the introduction of the National HPV Vaccination Program. A separate report published in the Kirby Institute’s Annual Surveillance Report 2011 (page 28) found the diagnosis of genital warts (caused by HPV types 6 and 11) had also decreased in young women and men.

In October 2010, the Australian regulatory agency, the Therapeutic Goods Administration, extended the registration of the quadrivalent vaccine (Gardasil) to include use in males aged 9 through 26 years of age, for the prevention of external genital lesions and infection with HPV types 6, 11, 16 and 18.

In November 2011, the Pharmaceutical Benefits Advisory Committee (PBAC) recommended the extension of the National HPV Vaccination Program to include males. The PBAC made its recommendation on the preventative health benefits that can be achieved, such as a reduction in the incidence of anal and penile cancers and other HPV-related disease. In addition to the direct benefit to males, it was estimated that routine HPV vaccination of adolescent males would contribute to the reduction of vaccine HPV-type infection and associated disease in women through herd immunity.

On 12 July 2012, the Australian Government announced funding to extend the National HPV Vaccination Program to include males, with implementation commencing in all states and territories in February 2013.

From February 2013, free HPV vaccine is being provided through school-based programs for:

• males and females aged 12-13 years (ongoing program); and
• males aged between 14-15 years – until the end of the school year in 2014 (catch up program).

Further information is available on the HPV Vaccination Program website at www.australia.gov.au/hpv

Canada

Canada has approved use of Gardasil. 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, 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. The cost for the 3 required shots is reported to be $510.00 .

Europe

United Kingdom

In the UK the vaccine is licensed for girls aged 9 to 15, for women aged 16 to 26, and for boys aged 9–15.

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.

From September 2012, Gardasil will replace Cervarix as the HPV vaccination of choice due to its added protection against genital warts.

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.

Israel

Introduced in 2012. Target age group 12. Fully financed by national health authorities.

Japan

Introduced in 2010, widely available only since April 2013. Fully financed by national health authorities. However in June 2013 Japan suspended recommendation of the vaccine.

Kenya

Both Cervarix and Gardasil are approved for use within Kenya by the Pharmacy and Poisons 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.

Laos

In 2013 Laos began implementation of the HPV vaccine, with the assistance of the Gavi Alliance.

Mexico

The vaccine was introduce in 2008 to 5% of the population. This percentage of the population had the lowest development index which leads to the highest incidence of cervical cancer. The HPV vaccine is deliver to girls 12 – 16 years old following the 0-2-6 dosing schedule. By 2009 Mexico had expanded the vaccine use to girls, 9 –12 years of aged, the dose schedule in this group was different, the time elapse between the first and second dose was six months and the third dose 60 months later. In 2011 Mexico approved a nationwide use of HPV vaccination program to include vaccination of all 9-year-old girls.

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.

Panama

The vaccine was added to the national immunization program in 2008, to target girls in the population aged 10. The vaccine is being administer by clinics and schools.

South Africa

Cervical cancer represents the most common cause of cancer-related deaths - more than 3,000 deaths per year - among women in South Africa because of high HIV prevalence, making introduction of the vaccine highly desirable. A Papanicolaou test program was established in 2000 to help screen for cervical cancer, but since this program has not been implemented widely, vaccination would offer more efficient form of prevention. In May 2013 the Minister of Health of South Africa, Aaron Motsoaledi, announced the government would provide free HPV vaccines for girls aged 9 and 10 in the poorest 80% of schools starting in February 2014 and the fifth quintile later on. South Africa will be the first African country with an immunisation schedule that includes vaccines to protect people from HPV infection, but because the effectiveness of the vaccines in women who later become infected with HIV is not yet fully understood, it is difficult to assess how cost-effective the vaccine will be. Negotiations are currently underway for more affordable HPV vaccines since they are up to 10 times more expensive than others already included in the immunisation schedule.

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. Approval for use in boys was based on safety and immunogenicity but not efficacy.

Trinidad and Tobago

Introduced in 2013. Target Group 9-26. Fully financed by national health authorities. Administration in schools currently suspended owing to objections and concerns raised by the Catholic Board, but fully available in local health centers.

United States

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

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).

A survey was conducted in 2009 to gather 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 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 overestimate the protection provided by the vaccine. Despite moderate uptake, many females at risk of acquiring HPV have not yet received the vaccine.

Since the approval of Gardasil in 2006 and despite low vaccine uptake, prevalence of HPV among teenagers aged 14-19 has been cut in half with an 88% reduction among vaccinated women. No decline in prevalence was observed in other age groups, indicating the vaccine to have been responsible for the sharp decline in cases. The drop in number of infections is expected to in turn lead to a decline in cervical and other HPV-related cancers in the future.

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. Only two such bills passed (in Virginia and Washington DC) during the first four years after vaccine introduction. Mandates have been effective at increasing uptake of other vaccines, such as mumps, measles, rubella, and hepatitis B (which is also sexually transmitted). 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.

Other measures that have been considered include requiring insurers to cover HPV vaccination, and funding HPV vaccines for those without insurance. The cost of the HPV vaccines for females under 18 who are uninsured is covered under the federal Vaccines for Children Program. As of 23 September 2010, vaccines are required to be covered by insurers under the Patient Protection and Affordable Care Act. HPV vaccines specifically are to be covered at no charge for women, including those who are pregnant or nursing.

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.

State-by-State

The National Conference of State Legislatures periodically issues summaries of HPV vaccine related legislation.

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

Source: National Conference of 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. The Centers for Disease Control and Prevention repealed all HPV vaccination directives for immigrants effective December 14, 2009.

Opposition in the United States

Health insurance companies

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

However, Medicaid covers HPV vaccination in accordance with the ACIP recommendations, and immunizations are a mandatory service under Medicaid for eligible individuals under age 21. In addition, Medicaid includes the Vaccines for Children Program. This program provides immunization services for children 18 and under who are Medicaid eligible, uninsured, underinsured, receiving immunizations through a Federally Qualified Health Center or Rural Health Clinic, or are Native American or Alaska Native.

The vaccine manufacturers also offer help for people who cannot afford HPV vaccination. GSK has the Vaccines Access Program, which provides Cervarix free of charge to women who do not have insurance and who have a low income, and who are ages 19 to 25 and therefore too old for the Medicaid Vaccines for Children Program. For example, Merck offers the Merck Vaccine Patient Assistance Program, which provides Gardasil for free to people over the age of 19 who do not have health insurance or cannot afford to pay for the vaccine.

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.

Many organizations 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."

Future

Merck is currently conducting phase III trials on a new HPV (Human Papillomavirus) Nonavalent (Types 6, 11, 16, 18, 31, 33, 45, 52, and 58) Recombinant Vaccine called V503 with results due in 2013.

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External links

This article's use of external links may not follow Misplaced Pages's policies or guidelines. Please improve this article by removing excessive or inappropriate external links, and converting useful links where appropriate into footnote references. (October 2010) (Learn how and when to remove this message)

• 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.

• Misplaced Pages external links cleanup from October 2010
• Gynaecological cancer
• Papillomavirus
• Vaccines
• Cancer vaccines