Human papillomavirus (HPV) vaccines are vaccines intended to provide acquired immunity against infection by certain types of human papillomavirus (HPV).[20] The first HPV vaccine became available in 2006.[20][21] Currently there are six licensed HPV vaccines: three bivalent (protect against two types of HPV), two quadrivalent (against four), and one nonavalent vaccine (against nine)[22][23] All have excellent safety profiles and are highly efficacious, or have met immunobridging standards.[20]:668 All of them protect against HPV types 16 and 18, which are together responsible for approximately 70% of cervical cancer cases globally.[22] The quadrivalent vaccines provide additional protection against HPV types 6 and 11.[22] The nonavalent provides additional protection against HPV types 31, 33, 45, 52 and 58.[22] It is estimated that HPV vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and show more than 90% effectiveness in preventing HPV-positive oropharyngeal cancers.[24][25][26][27] They also protect against penile cancer.[28]They additionally preventgenital warts (also known as anogenital warts), with the quadrivalent and nonavalent vaccines providing virtually complete protection.[22][20] The WHO recommends a one or two-dose schedule for girls aged 9–14 years, the same for girls and women aged 15–20 years, and two doses with a 6-month interval for women older than 21 years.[29][20] The vaccines provide protection for at least five to ten years.[20]
The primary target group in most of the countries recommending HPV vaccination is young adolescent girls, aged 9–14.[22] The vaccination schedule depends on the age of the vaccine recipient.[22] As of 2023, 27% of girls aged 9–14 years worldwide received at least one dose (37 countries were implementing the single-dose schedule, 45% of girls aged 9–14 years old vaccinated in that year).[30][31] As of September 2024, 57 countries are implementing the single-dose schedule.[30] At least 144 countries (at least 74% of WHO member states) provided the HPV vaccine in their national immunization schedule for girls, as of November 2024.[32][31] As of 2022, 47 countries (24% of WHO member states) also did it for boys.[20]:654 Vaccinating a large portion of the population may also benefit the unvaccinated by way of herd immunity.[33]
The HPV vaccine is on the World Health Organization's List of Essential Medicines.[34] The World Health Organization (WHO) recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures.[20] The WHO's priority purpose of HPV immunization is the prevention of cervical cancer, which accounts for 82% of all HPV-related cancers and more than 95% of which are caused by HPV.[20][30] 88% (2020 figure) of cervical cancers and 90% of deaths occur in low- and middle-income countries and 2% (2020 figure) in high-income countries.[20]:650[30] The WHO-recommended primary target population for HPV vaccination is girls aged 9–14 years before they become sexually active.[20]:669 It aims the introduction of the HPV vaccine in all countries and has set a target of reaching a coverage of 90% of girls fully vaccinated with HPV vaccine by age 15 years.[31][35] Females aged ≥15 years, boys, older males or men who have sex with men (MSM) are secondary target populations.[20] HPV vaccination is the most cost-effective public health measure against cervical cancer, particularly in resource-constrained settings.[36][20]:666Cervical cancer screening is still required following vaccination.[20]
Preventive vaccines
A growing number of vaccine products initially prequalified for use in a 2-dose schedule can now be used in a single-dose schedule.[30] Cecolin (WHO prequalified HPV vaccine product, confirmed for use in a single-dose schedule), in the second edition of WHO's technical document on considerations for HPV vaccine product choice[30]Cervarix (bivalent)[30]Gardasil (quadrivalent) and Gardasil 9 nonavalent vaccine)[30] Walrinvax (WHO prequalified with a two-dose schedule on 2 August 2024)[30]
Medical uses
Gardasil 9A Gardasil Syringe
HPV vaccines are used to prevent HPV infection and therefore in particular cervical cancer.[20] Vaccinating females between the ages of nine to thirteen is typically recommended, with many countries also vaccinating males in that age range.[20] In the United States, the Centers for Disease Control and Prevention (CDC) recommends that all 11- to 12-year-olds receive two doses of HPV vaccine, administered 6 to 12 months apart.[37] The vaccines require three doses for those ages 15 and above.[20] Gardasil is a three-dose (injection) vaccine. HPV vaccines are recommended in the United States for women and men who are 9–26 years of age and are also approved for those who are 27–45 years of age.[38][39]
HPV vaccination of a large percentage of people within a population has been shown to decrease rates of HPV infections, with part of the benefit from herd immunity.[20][40] Since the vaccines only cover some high-risk types of HPV, cervical cancer screening is recommended even after vaccination.[20][41] In the US, the recommendation is for women to receive routine Pap smears beginning at age 21.[42] In Australia, the national screening program has changed from the two yearly cytology (pap smears) to being based on tests for HPV DNA,[43] based on work by Karen Canfell and others.[44] As of 2021, the World Health Organization recommends HPV DNA testing as the preferred screening method.[45][46]
HPV adolescent girls vaccination rates (2023 estimated figures) and cervical cancer cases per 100,000 people across global regions (2021 figures).
Efficacy
The HPV vaccine has been shown to prevent cervical dysplasia from the high-risk HPV types 16 and 18 and provide some protection against a few closely related high-risk HPV types.[20][47] However, other high-risk HPV types are not affected by the vaccine.[48] The protection against HPV 16 and 18 has lasted at least eight years after vaccination for Gardasil[49] and more than nine years for Cervarix.[49] It is thought that booster vaccines will not be necessary.[50]
As of September 2024, 57 countries are implementing the single-dose schedule.[30] A growing number of vaccine products initially prequalified for use in a 2-dose schedule can now be used in a single-dose schedule.[30] Before, it was unsure whether two doses of the vaccine may work as well as three doses.[51] The US Centers for Disease Control and Prevention (CDC) recommends two doses in those less than 15 years and three doses in those over 15 years.[52] A single dose might be effective.[53][54][55][56]
A study with 9vHPV, a 9-valent HPV vaccine that protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, came to the result that the rate of high-grade cervical, vulvar, or vaginal disease was the same as when using a quadrivalent HPV vaccine.[57] A lack of a difference may have been caused by the study design of including women 16 to 26 years of age, who may largely already have been infected with the five additional HPV types that are additionally covered by the 9-valent vaccine.[58]
Neither Cervarix nor Gardasil prevent other sexually transmitted infections, and they do not treat existing HPV infections or cervical cancer.[59][60]
Gardasil
When Gardasil was first introduced, it was recommended as a prevention for cervical cancer for women 25 years old or younger.[39] Evidence suggests that HPV vaccines are effective in preventing cervical cancer for women up to 45 years of age.[38]Gardasil and Gardasil 9 protect against HPV types 6 and 11 which can cause genital warts, with the quadrivalent and nonavalent vaccines providing virtually complete protection.[22][13][14][20]
Adenocarcinoma
HPV types 16, 18, and 45 contribute to 94% of cervical adenocarcinoma (cancers originating in the glandular cells of the cervix).[61] While most cervical cancer arises in the squamous cells, adenocarcinomas make up a sizable minority of cancers.[61] 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.[61] Trials suggest that HPV vaccines may also reduce the incidence of adenocarcinoma.[61]
Males
As of 2022, 47 countries (24% of WHO member states) have introduced HPV vaccine in their national immunization programme for boys.[20]:654 For instance, it is the case in Switzerland, Portugal, Canada, Australia, Ireland, South Korea, Hong Kong, the United Kingdom, New Zealand, the Netherlands, and the United States.[62][63]
In males also, Gardasil and Gardasil 9 protect against HPV types 6 and 11 which can cause genital warts, with the quadrivalent and nonavalent vaccines providing virtually complete protection.[22][13][14][20] They reduce their risk of precancerous lesions caused by HPV. This reduction in precancerous lesions is predicted to reduce the rates of penile and anal cancer in men. Gardasil has been shown to also be effective in preventing high-risk HPV types 16 and 18 in males.[64][65][66][67][68][69] While Gardasil and the Gardasil 9 vaccines have been approved for males, a third HPV vaccine, Cervarix, has not. Unlike the Gardasil-based vaccines, Cervarix does not protect against genital warts.[70]
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.[71]
Gardasil is also used among men who have sex with men (MSM), who are at higher risk for genital warts, penile cancer, and anal cancer.[72]
Recommendations by national bodies
Australia
Australia introduced HPV vaccination for boys in 2013.[73]
Ireland
Ireland introduced HPV vaccination for boys aged 13 as part of their National Immunization Plan in 2019.[74]
UK
UK introduced HPV vaccination for boys aged 12 as part of their National Immunization Plan in 2019.[75]
Portugal
Portugal introduced universal HPV vaccination for boys aged 10 years and above as part of its National Immunization Plan in 2020.[76]
United States
On 9 September 2009, an advisory panel recommended that the Food and Drug Administration (FDA) of the USA license Gardasil in the United States for boys and men ages 9–26 for the prevention of genital warts.[77] Soon after that, the vaccine was approved by the FDA for use in males aged 9 to 26 for prevention of genital warts[64][65] and anal cancer.[78][79][80]
In 2011, an advisory panel for the US Centers for Disease Control and Prevention (CDC) recommended the vaccine for boys ages 11–12.[39] This was 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).[81] 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.[64][82] For those under the age of 27 who have not been fully vaccinated the CDC recommends vaccination.[39]
Also in 2011, Harald zur Hausen's support for vaccinating boys (so that they will be protected, and thereby so will women) was joined by professors Harald Moi and Ole-Erik Iversen.[83]
In 2018, the US Food and Drug Administration (FDA) released a summary basis for regulatory action and approval for expansion of usage and indication for Gardasil 9, the 9-valent HPV vaccine, to include men and women 27 to 45 years of age.[84]
Public health
World Health Organization (WHO)
The HPV vaccine is on the WHO Model List of Essential Medicines.[34] The WHO recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures.[20] The WHO's priority purpose of HPV immunization is the prevention of cervical cancer, which accounts for 82% of all HPV-related cancers and more than 95% of which are caused by HPV.[20][30] The WHO has a global strategy for cervical cancer elimination.[30] Its first pillar is having 90% of girls fully vaccinated with the HPV vaccine by 15 years of age.[30] The WHO-recommended primary target population for HPV vaccination is girls aged 9–14 years before they become sexually active.[20]:669 Females aged ≥15 years, boys, older males or MSM are secondary target populations.[20]Cervical cancer screening is still required following vaccination.[20]
Global
Cervical cancer
The large majority of cervical cancer cases in 2020 (88%) occurred in LMICs, where they account for 17% of all cancers in women, compared with only 2% in high-income countries (HICs). In sub-Saharan Africa, the region with the highest rates of young WLWH, approximately 20% of cervical cancer cases occur in WLWH [women living with HIV]. HPV infection is more likely to persist and to progress to cancer in WLWH.33 Mortality rates vary 50-fold between countries, ranging from <2 per 100 000 women in some HICs to >40 per 100 000 in some countries of sub-Saharan Africa.
Of the 20 hardest hit countries by cervical cancer, 19 are in Africa.[30]
The US 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."[41]
In 2004, preventive vaccines already protected against the two HPV types (16 and 18) that cause about 70% of cervical cancers worldwide.[85] Because of the distribution of HPV types associated with cervical cancer, the vaccines were likely to be most effective in Asia, Europe, and North America.[85] Some other high-risk types cause a larger percentage of cancers in other parts of the world.[85] Vaccines that protect against more of the types common in cancers would prevent more cancers, and be less subject to regional variation.[85] 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.[85]
In 2008, only 41% of women with cervical cancer in the developing world got medical treatment.[86] 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.[87] However, individuals in many resource-limited nations, Kenya for example, are unable to afford the vaccine.[88]
In more developed countries, populations that do not receive adequate medical care, such as the 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.[61] In 2009, Dr. Diane Harper, a researcher for the HPV vaccines, questioned whether the benefits of the vaccine outweigh its risks in countries where Pap smear screening is common.[89] She has also encouraged women to continue pap screening after they are vaccinated and to be aware of potential adverse effects.[90]
United States
In 2012, according to the CDC, the use of the HPV vaccine had cut rates of infection with HPV-6, -11, -16, and -18 in half in American teenagers (from 11.5% to 4.3%) and by one-third in American women in their early twenties (from 18.5% to 12.1%).[91]
Side effects
HPV vaccines are safe and well tolerated and can be used in persons who are immunocompromised or HIV-infected.[92] Pain at the site of injection occurs in between 35% and 88% of people[20]:664 Redness and swelling at the site and fever may also occur.[20] No link to Guillain–Barré syndrome has been found.[20] There is no increased risk of serious adverse effects.[47] Extensive clinical trial and post-marketing safety surveillance data indicate that both Gardasil and Cervarix are well tolerated and safe.[47][93] When comparing the HPV vaccine to a placebo (control) vaccine taken by women, there is no difference in the risk of severe adverse events.[47]
United States
As of 8September2013[update], there were more than 57 million doses of Gardasil vaccine distributed in the United States, though it is unknown how many were administered.[94] There have been 22,000 Vaccine Adverse Event Reporting System (VAERS) reports following the vaccination.[95] 92% 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 the rest were considered to be serious (death, permanent disability, life-threatening illness, and hospitalization). However, VAERS reports include any reported effects whether coincidental or causal. In response to concerns regarding the rates of adverse events associated with the vaccine, the CDC stated: "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."[95]
As of 1September2009[update], in the US there were 44 reports of death in females after receiving the vaccine.[95] None of the 27 confirmed deaths of women and girls who had taken the vaccine were linked to the vaccine.[95] There is no evidence suggesting that Gardasil causes or raises the risk of Guillain–Barré syndrome. Additionally, there have been rare reports of blood clots forming in the heart, lungs, and legs.[95] A 2015 review conducted by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee concluded that evidence does not support the idea that HPV vaccination causes complex regional pain syndrome or postural orthostatic tachycardia syndrome.[96]
As of 8September2013[update], the CDC continued to recommend Gardasil vaccination for the prevention of four types of HPV.[95] The manufacturer of Gardasil has committed to ongoing research assessing the vaccine's safety.[97]
According to the Centers for Disease Control and Prevention (CDC) and the FDA, the rate of adverse side effects related to Gardasil immunization in the safety review was 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) was seen with Gardasil than is usually seen with other vaccines. The FDA and CDC have reminded healthcare 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.[60] The HPV vaccination does not appear to reduce the willingness of women to undergo pap tests.[98]
Contraindications
While the use of HPV vaccines can help reduce cervical cancer deaths by two-thirds around the world,[99] not everyone is eligible for vaccination. Some factors exclude people from receiving HPV vaccines. These factors include:[100]
People with moderate or severe acute illnesses. This does not completely exclude patients from vaccination but postpones the time of vaccination until the illness has improved.[101]
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 a placebo.[102][103] However, the clinical trials had a relatively small sample size. As of 2018[update], the vaccine is not recommended for pregnant women.[47][102][104][105]
The FDA has classified the HPV vaccine as a pregnancy Category B, meaning there is no apparent harm to the fetus in animal studies. HPV vaccines have not been causally related to 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 should be postponed until pregnancy has been completed. While there is no indication for intervention for vaccine dosages administered during pregnancy, patients and healthcare providers are encouraged to report exposure to vaccines to the appropriate HPV vaccine pregnancy registry.[100][101][106]
Mechanism of action
The HPV vaccines are based on hollow virus-like particles (VLPs) assembled from recombinant HPV coat proteins. The natural virus capsid is composed of two proteins, L1 and L2, but vaccines only contain L1.
Gardasil contains inactive L1 proteins from four different HPV strains: 6, 11, 16, and 18, synthesized in the yeast Saccharomyces cerevisiae. Each vaccine dose contains 225μg of aluminum, 9.56mg of sodium chloride, 0.78mg of L-histidine, 50μg of polysorbate 80, 35μg of sodium borate, and water. The combination of ingredients totals 0.5mL.[107] HPV types 16 and 18 cause about 70% of all cervical cancer.[85] Gardasil also targets HPV types 6 and 11, which together cause about 90 percent of all cases of genital warts.[108]
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.[48]
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.[109]
History
In the 1983, Harald zur Hausen culminated decades of research with the discovery that certain variants of human papillomaviruses (HPVs) could be found in a majority of tested cervical cancer specimens. This provided strong scientific evidence for a link between the viral infection and cervical cancer, and provided strong motivations for further research into HPVs.[110]
In 1990, Ian Frazer partnered with Jian Zhou and Xiao-Yi Sun at the University of Queensland in Australia to create synthetic HPVs for study in the lab. While working towards this goal, they were able to synthetically produce some of the capsid proteins of the HPVs, L1 and L2. Recognizing the potential of these proteins to form the basis of a vaccine, they filed a provisional patent on their production process in Australia in 1991.[110]
The further invention then stalled while convincing developers of the market for the vaccine, and also while patent offices determined who the discovery belonged to. Three other organizations, the US National Cancer Institute, Georgetown University, and University of Rochester, were also vying for the patent as a result of contributions in the space.[111] After providing evidence of the correctness of their L1 sequencing in 2004, the US patent court of appeals accorded priority to the University of Queensland in 2009.[112] As a result, the University of Queensland receives royalty payments from the sale of these vaccines even today.[110]
By the early 2000s, developers, convinced of the market of the vaccine, had begun refining, researching, and trialing L1-based HPV vaccines.[113][48] In 2006, the FDA approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil. According to a Merck press release,[114] by 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 licensed in Australia, and it was approved in the European Union in September 2007.[115] Cervarix was approved for use in the US in October 2009.[116]
Harald zur Hausen was awarded half of the $1.4million Nobel Prize in Medicine in 2008 for his work showing that cervical cancer is caused by certain types of HPVs. [117]
In December 2014, the US Food and Drug Administration (FDA) approved a vaccine called Gardasil 9 to protect females between the ages of 9 and 26 and males between the ages of 9 and 15 against nine strains of HPV.[118] Gardasil 9 protects against infection from the strains covered by the first generation of Gardasil (HPV-6, HPV-11, HPV-16, and HPV-18) and protects against five other HPV strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58).[118]
Society and culture
Economics
As of 2013[update], vaccinating girls and young women was estimated to be cost-effective in the low and middle-income countries, especially in places without organized programs for screening cervical cancer.[119] When the cost of the vaccine itself, or the cost of administering it to individuals, were higher, or if cervical cancer screening were readily available, then vaccination was less likely to be cost-effective.
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 to vaccinate men when the uptake in the female population is extremely low.[120] In the United States, the cost per quality-adjusted life year is greater than US$100,000 for vaccinating the male population, compared to the less than US$50,000 for vaccinating the female population.[120] This assumes a 75% vaccination rate.
In 2013, the two companies that sell the most common vaccines announced a price cut to less than US$5 per dose to poor countries, as opposed to US$130 per dose in the US.[121]
Brand names
The vaccine is sold under various brand names including Gardasil, Cervarix, Cecolin,[30] and Walrinvax.[30][22]
The primary target group in most of the countries recommending HPV vaccination is young adolescent girls, aged 9–14.[22] It's particularly cost-effective in resource-constrained settings.[20]:666 The vaccination schedule depends on the age of the vaccine recipient.[22] As of 2023, 27% of girls aged 9–14 years worldwide received at least one dose (37 countries were implementing the single-dose schedule).[30] Global coverage for the first dose of HPV vaccine in girls grew from 20% in 2022 to 27% in 2023.[31] As of 10 September 2024, 57 countries are implementing the single-dose schedule.[30] Vaccinating a large portion of the population may also benefit the unvaccinated by way of herd immunity.[33]
HPV vaccine introductions have been hampered by global supply shortages since 2018.[30] Between 2019 and 2021, due to the COVID-19 pandemic, HPV vaccination programs have been significantly affected in the United States, low-income and lower-middle-income countries.[122][123][124][125]
In developed countries, the widespread use of cervical "Pap smear" screening programs has reduced the incidence of invasive cervical cancer by 50% or more. 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.[126] School-entry vaccination requirements were found to increase the use of the HPV vaccine.[127][128]
HPV vaccine included in national immunization program
At least 144 countries (at least 74% of WHO member states) provided the HPV vaccine in their national immunization schedule for girls, as of November 2024.[32][31] As of 2022, 47 countries (24% of WHO member states) also did it for boys.[20]:654
Africa
Of the 20 hardest hit countries by cervical cancer, 19 are in Africa.[30] In 2013, with support from Gavi, the Vaccine Alliance, eight low-income countries, mainly in sub-Saharan Africa, began the rollout of the HPV vaccine.[129]
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.[88] It has received GAVI support in 2013.[129]
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 the introduction of the vaccine highly desirable.[131] 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.[132] 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.[133] 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[when?] underway for more affordable HPV vaccines since they are up to 10 times more expensive than others already included in the immunization schedule.[131][133]
Yes (GAVI support for HPV demonstration projects in 2014)[130][129]
Australia
In April 2007, Australia became the second country—after Austria—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.[134] The National HPV Vaccination Program is listed on the National Immunisation Program (NIP) Schedule and funded under the Immunise Australia Program.[135] The Immunise Australia Program is a joint Federal, 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- and 13-year-old girls; and a time-limited catch-up program (females aged 14–26 years) delivered through schools, general practices, and community immunization 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.[134] By 2017, HPV coverage data on the Immunise Australia website show that by 15 years of age, over 82% of Australian females had received all three doses.[136]
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 Diseases 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.[134] A 2011 report published found the diagnosis of genital warts (caused by HPV types 6 and 11) had also decreased in young women and men.[137]
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 preventive health benefits that can be achieved, such as a reduction in the incidence of anal and penile cancers and other HPV-related diseases. 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.[138]
In 2012, the Australian Government announced it would be extending the National HPV Vaccination Program to include males, through the National Immunisation Program Schedule.[139]
Since February 2013, free HPV vaccine has been provided through school-based programs for:
males and females aged 12–13 years (ongoing program); and
males aged between 14 and 15 years – until the end of the school year in 2014 (catch-up program).
Canada
HPV vaccines were first approved in Canada in July 2006 for use in females,[141] and February 2010 for use in males.[142]
The vaccines Cervarix, Gardasil, and Gardasil 9 are authorized for use in Canada,[143] with Gardasil 9 the primary vaccine used.[144] All provinces and territories (except Quebec) administer Gardasil 9 on a two or three-dose schedule: individuals under age 15 are given two doses, while individuals who are immunocompromised, living with HIV, or age 15+ are given three doses. Quebec provides two doses to individuals under 18 years (the first dose is Gardasil 9, and the second dose is Cervarix) and three doses of Gardasil 9 to people age 18+.[144]
The administration of free vaccination programs is provided by individual province and territory governments. All provincial and territorial governments offer free vaccination for school-aged children, irrespective of gender.[145] The school grades in which the vaccine is provided varies by province and territory: grade 4 and secondary 3 (Quebec); grade 6 (British Columbia, Manitoba, Newfoundland and Labrador, Nunavut, Prince Edward Island, Saskatchewan, Yukon); grades 6 and 9 (Alberta); grades 4-6 (Northwest Territories); or grade 7 (New Brunswick, Nova Scotia, Ontario).[144] Publicly funded HPV vaccines are also provided in certain provinces and territories for other groups of people, such as men who have sex with men, individuals living with HIV, and individuals who identify as transgender. Individuals who do not qualify for any of the publicly funded programs can privately purchase the three-dose HPV vaccine series for $510 to $630.[144]
China
GlaxoSmithKline China announced in 2016, that Cervarix (HPV vaccine 16 and 18) had been approved by the China Food and Drug Administration (CFDA).[146] Cervarix is registered in China for girls aged 9 to 45, adopting 3-dose program within 6 months.[147] Cervarix was launched in China in 2017, and it was the first approved HPV vaccine in China.[148]
Colombia
The vaccine was introduced in 2012, approved for girls aged 9.[149][150] The HPV vaccine was initially offered to girls aged 9 and older, and attending the fourth grade of school. Since 2013 the age of coverage was extended to girls in school from grade four (who have reached the age of 9) to grade eleven (independent of age); and no schooling from age 9–17 years 11 months and 29 days old.[151]
Costa Rica
Since June 2019, the vaccine is administered compulsorily by the state, free of charge to girls at ten years of age.[152][153]
Finland, Hungary, Iceland, Malta, Norway, Portugal, Spain, Sweden and the UK have reported national coverage above 70%. In some countries, including France and Germany, coverage has been consistently below 50%, though recently increasing in France.
Fully financed by national health authorities for 7th grade schoolgirls (12–13 years old).[166][168] Several local governments have decided to pursue their own earlier initiative, thus providing the vaccine to those who are not eligible for the national vaccination programme due to their age.[168] Subsidised by some local councils for 13- and 14-year-olds.
Offered to males and females in the first year of secondary school. Non-mandatory. HPV vaccination was introduced to the national immunisation scheme for males in 2019.
The school-based vaccination program is fully financed by national health authorities, initially for girls only. Offered to all children in fifth grade from August 2020 (boys born in 2009 are included).[174]
All vaccinations within the national vaccination programme for children are voluntary.
Fully financed by national health authorities initially for girls only. Offered to boys aged 12 and 13 years from September 2019.[175] The HPV vaccine is available for free on the NHS up until a person's 25th birthday if they were eligible and missed the HPV vaccine offered in Year 8 at school,:[176]
girls born after 1 September 1991
boys born after 1 September 2006
Also fully financed by national health authorities since 2018 for men aged up to and including 45 years of age who have sex with other men (MSM) when they visit sexual health clinics and HIV clinics in England. Trans women (people who were assigned male at birth) are eligible in the same way as MSM if their risk of getting HPV is similar to the risk of MSM who are eligible for the HPV vaccine. Trans men (people who were assigned female at birth) are eligible if they have sex with other men and are aged 45 or under.[176]
Offered to males and females in the second year of secondary school, as well as at sexual health and HIV clinics in England. Non-mandatory.
Hong Kong
HPV vaccines are approved for use in Hong Kong. As part of the Hong Kong Childhood Immunisation Programme, HPV vaccines became mandatory for students in the 2019/2020 school year, exclusively for females at primary 5 and 6 levels.[177]
India
HPV vaccine (both Gardasil and Cervarix) was introduced in Indian markets in 2008, but it is yet to be included in the country's universal immunization programme. In Punjab and Sikkim (states of India), it is included in the state immunization program and the coverage is up to 97% of targeted girls.[178] HPV vaccination has been recommended by the National Technical Advisory Group on Immunization, but has not been implemented in India as of 2018.[179]
In 2023, Serum Institute of India (SII) developed a new vaccine Cervavax targeting HPV types 6, 11, 16, and 18. The newly developed vaccine shows equal capability to Merck's Gardasil 9. Cervavax vaccine isn't commercially available yet.[180] In 2024, the HPV vaccine drive was announced by Finance Minister Nirmala Sitharaman as part of Nari Shakti ("Women Power") campaign but hasn't been implemented yet. The vaccine is commercially available in the market at a price between ₹ 3,000 ($35) and ₹ 15,000 ($180).
Ireland
The HPV vaccination programme in Ireland is part of the national strategy to protect females from cervical cancer. Since 2009, the Health Service Executive has offered the HPV vaccine, free of charge, to all girls from the first year onwards (ages 12–13). Secondary schools began implementing the vaccine program on an annual basis from September 2010 onwards.[181] The programme was expanded to include males in 2019.[182] Two HPV vaccines are licensed for use in Ireland: Cervarix and Gardasil. To ensure high uptake, the vaccine is administered to teenagers aged 12–13 in their first year of secondary school, with the first dose administered between September and October and the final dose in April of the following year.[182][183] Males and females aged 12–13 who are outside of the traditional school setting (home school, etc.) are invited to Health service Executive clinics for their vaccines. HPV vaccination in Ireland is not mandatory and consent is obtained before vaccination.[169][182] For males and females aged 16 and under, consent is granted by a parent or guardian unless it is explicitly refused by the child. Any male or female aged 16 and over may provide their own consent if they want to be vaccinated.[182]HIQA has stated the vaccine will provide further protection, particularly to men who have sex with men. The vaccine has been extended following evidence that 25% of HPV cancers occur in men.[184] Additionally, HIQA is aiming to replace the current vaccination, which covers 4 major HPV strains, with an updated vaccine protecting against nine strains. The cost with the "gender-neutral nine-talent" vaccine is estimated to be nearly €11.66million over the next five years.[169]
Israel
Introduced in 2012. Target age group 13–14. Fully financed by national health authorities only for this age group. For the year 2013–2014, girls in the eighth grade may get the vaccine free of charge only in school, and not in Ministry of Health offices or clinics. Girls in the ninth grade may receive the vaccine free of charge only at Ministry of Health offices, and not in schools or clinics.[185] Religious and conservative groups are expected to refuse the vaccination.[186]
Japan
The quadrivalent vaccine has been approved for males and the 9-valent one for females.[187] Since 2010, young women in Japan have been eligible to receive the cervical cancer vaccination for free.[188] In June 2013, the Japanese Ministry of Health, Labor and Welfare mandated that, before administering the vaccine, medical institutions must inform women that the ministry does not recommend it.[188] However, the vaccine is still available at no cost to Japanese women who choose to accept the vaccination.[188] It is widely available only since April 2013. Fully financed by national health authorities to females aged 11 to 16 years. In June 2013, however, Japan's Vaccine Adverse Reactions Review Committee (VARRC) suspended the recommendation of the vaccine due to fears of adverse events. This directive has been criticized by researchers at the University of Tokyo as a failure of governance since the decision was taken without the presentation of adequate scientific evidence.[189] At the time, Ministry spokespeople emphasized that "The decision does not mean that the vaccine itself is problematic from the viewpoint of safety," but that they wanted time to conduct analyses on possible adverse effects, "to offer information that can make the people feel more at ease."[190] However, the suspension of the Ministry's endorsement was still in place as of February 2019, by which time the HPV vaccination rate among younger women fell from approximately 70% in 2013 to 1% or less.[191] Over an overlapping time period (2009–2019), the age-adjusted mortality rate from cervical cancer increased by 9.6%.[191] Japan to Resume Active Promotion of HPV Vaccinations in April 2022.[192][193] In December 2021, the Ministry of Health, Labour and Welfare has decided to allow free vaccines to women born between fiscal year 1997 and 2005 after eight-year hiatus.[194] A panel of Japan's Ministry of Health, Labour and Welfare agreed to give women (born between fiscal 1997 and fiscal 2005), free vaccinations, if they missed the country's free vaccination program.[195] 225,993 girls were vaccinated for the first round of routine vaccination in 2022, and the vaccination rate was 42.2%.[196] The Osaka University Graduate School of Medicine and Faculty of Medicine reported the first vaccination rate and cumulative first vaccination rate for each year of birth in 2022 at a meeting of the Ministry of Health, Labor and Welfare. For 12-year-old girls born in 2010, the rate was 2.8%.[197]
Human Papillomavirus Vaccination by Birth Fiscal Year in Japan[198][199]
In 2010, Malaysia launched a national vaccination program to provide three doses of HPV vaccines to all 13-year-old girls. In 2015, the program transitioned to a two-dose regimen.[200]
High rates of school enrolment for 13-year-olds (96.0%) and retention of female students in secondary schools have made it possible for the HPV vaccination to be integrated into the School Health Service Program and ensure equal access to the HPV vaccine between urban and rural areas.[201]
Mexico
The vaccine was introduced in 2008 to 5% of the population. This percentage of the population had the lowest development index which correlates with the highest incidence of cervical cancer.[202] The HPV vaccine is delivered 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 age, the dosing schedule in this group was different, the time elapsed between the first and second dose was six months, and the third dose 60 months later.[203] In 2011 Mexico approved a nationwide use of HPV vaccination program to include vaccination of all 9-year-old girls.[203]
New Zealand
Immunization as of 2017 is free for males and females aged 9 to 26 years.[204]
The public funding began on 1 September 2008. The vaccine was initially offered only to girls, usually through a school-based program in Year 8 (approximately age 12), but also through general practices and some family planning clinics. Over 200,000 New Zealand girls and young women have received HPV immunization.[204]
Panama
The vaccine was added to the national immunization program in 2008, to target 10-year-old girls.[202]
South Korea
On 27 July 2007, South Korean government approved Gardasil for use in girls and women aged 9 to 26 and boys aged 9 to 15.[205] Approval for use in boys was based on safety and immunogenicity but not efficacy.
Since 2016, HPV vaccination has been part of the National Immunization Program, offered free of charge to all children under 12 in South Korea, with costs fully covered by the Korean government.[206]
For 2016 only, Korean girls born between 1 January 2003 and 31 December 2004 were also eligible to receive the free vaccinations as a limited-time offer. From 2017, the free vaccines are available to those under 12 only.[207]
Trinidad and Tobago
Introduced in 2013. Target Group 9–26. Fully financed by national health authorities. But was suspended later on that year owing to objections and concerns raised by the Catholic Board, but fully available in local health centers.[208]
United Arab Emirates
The World Health Organization ranks cervical cancer as the fourth most frequent cancer among women in UAE, at 7.4 per 100,000 women,[209] and according to Abu Dhabi Health Authority, the cancer is also the seventh highest cause of death of women in the U.A.E.[210]
In 2007, the HPV vaccine was approved for girls and young women, 15 to 26 years of age, and offered optionally at hospitals and clinics.[211][212] Moreover, starting 1 June 2013, the vaccine was offered free of charge for women between the ages of 18 and 26, in Abu Dhabi.[213] However, on 14 September 2018, the U.A.E's Ministry of Health and Community Protection announced that HPV vaccine became a mandatory part of the routine vaccinations for all girls in the U.A.E.[214] The vaccine is to be administers to all school girls in the 8th grade girls, aged 13.[215]
United Kingdom
In the UK the vaccine is licensed for females aged 9–26, for males aged 9–15, and for men who have sex with men aged 18–45.[216]
HPV vaccination 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 was offered to girls aged between 16 and 18 from autumn 2009, and girls aged between 15 and 17 from autumn 2010. It will be many years before the vaccination programme affects cervical cancer incidence so women are advised to continue accepting their invitations for cervical screening.[217]Men who have sex with men up to and including the age of 45 became eligible for free HPV vaccination on the NHS in April 2018. They get the vaccine by visiting sexual health clinics and HIV clinics in England.[218] A meta-analysis of vaccinations for men who have sex with men showed that this strategy is most effective when combined with gender-neutral vaccination of all boys, regardless of their sexual orientation.[219]
From the 2019/2020 school year, it is expected that 12- to 13-year-old boys will also become eligible for the HPV vaccine as part of the national immunisation programme. This follows a statement by the Joint Committee on Vaccination and Immunisation.[220] The first dose of the HPV vaccine will be offered routinely to boys aged 12 and 13 in school year 8, in the same way that it is currently (May 2018) offered to girls.[218]Boots UK opened a private HPV vaccination service to boys and men aged 12–44 years in April 2017 at a cost of £150 per vaccination. In children aged 12–14 years two doses are recommended, while those aged 15–44 years a course of three is recommended.[221]
Cervarix was the HPV vaccine offered from its introduction in September 2008, to August 2012, with Gardasil being offered from September 2012.[218][222] The change was motivated by Gardasil's added protection against genital warts.[223]
As of late 2007[update], about one-quarter of US females aged 13–17 years had received at least one of the three HPV shots.[224]By 2014[update], the proportion of such females receiving an HPV vaccination had risen to 38%.[225] The government began recommending vaccination for boys in 2011; by 2014[update], the vaccination rate among boys (at least one dose) had reached 35%.[225]
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).[59][226] Community-based interventions can increase the uptake of HPV vaccination among adolescents.[227]
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.[228] For example, young black women are less likely to receive HPV vaccines compared to young white women. Additionally, young women of all races and ethnicities without health insurance are less likely to get vaccinated.[229]
As of 2017, Gardasil 9 is the only HPV vaccine available in the United States as it provides protection against more HPV types than the earlier approved vaccines (the original Gardasil and Cervarix).[230][231] 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.[232][233]
Legislation
Four states have laws that require HPV vaccination for school students:[231]Hawaii, Rhode Island, Virginia, and Washington D.C. Students in those states must have started HPV vaccination before entering the 7th grade. All school immunization laws grant exemptions to children for medical reasons, with other "opt-out" policies varying by state.[234]
Shortly after the first HPV vaccine was approved, bills to make the vaccine mandatory for school attendance were introduced in many states.[235] Only two such bills passed (in Virginia and Washington DC) during the first four years after vaccine introduction.[235] Mandates have been effective at increasing uptake of other vaccines, such as mumps, measles, rubella, and hepatitis B (which is also sexually transmitted).[226] 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.[235] Most public policies including school mandates have not been effective in promoting HPV vaccination while receiving a recommendation from a physician increased the probability of vaccination.[236]
In July 2015, Rhode Island added an HPV vaccine requirement for admittance into public schools. This mandate requires all students entering the seventh grade to receive at least one dose of the HPV vaccine starting in August 2015, all students entering the eighth grade to receive at least two doses of the HPV vaccine starting in August 2016, and all students entering the ninth grade to receive at least three doses of the HPV vaccine starting in August 2017.[128][237][238] No legislative action is required for the Rhode Island Department of Health to add new vaccine mandates. Rhode Island is the only state that requires the vaccine for both male and female 7th graders.[128]
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 to prevent diseases that are spread by respiratory route and considered highly contagious.[239] The Centers for Disease Control and Prevention repealed all HPV vaccination directives for immigrants effective 14 December 2009.[240] Uptake in the United States appears to vary by ethnicity and whether someone was born outside the United States.[241][242]
Coverage
Measures have been considered including 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.[243] 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.[244]
Medicaid covers HPV vaccination in accordance with the ACIP recommendations, and immunizations are a mandatory service under Medicaid for eligible individuals under age 21.[245] In addition, Medicaid includes the Vaccines for Children Program.[246] 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.[246]
The vaccine manufacturers also offer help for people who cannot afford HPV vaccination. GlaxoSmithKline's Vaccines Access Program[247] provides Cervarix[248] free of charge 1-877-VACC-911[249] to low-income women, ages 19 to 25, who do not have insurance.[250]Merck's Vaccine Patient Assistance Program 1-800-293-3881[251] provides Gardasil free to low-income women and men, ages 19 to 26, who do not have insurance, including immigrants who are legal residents.[252]
The idea that the HPV vaccine is linked to increased sexual behavior is not supported by scientific evidence. A review of nearly 1,400 adolescent girls found no difference in teen pregnancy, incidence of sexually transmitted infection, or contraceptive counseling regardless of whether they received the HPV vaccine.[253] Thousands of Americans die each year from cancers preventable by the vaccine.[253] A disproportionate rate of HPV-related cancers exists amongst LatinX populations, leading researchers to explore how communication and messaging can be adjusted to address vaccine hesitancy.[254]
Insurance companies
There has been significant opposition from health insurance companies to covering the cost of the vaccine ($360).[255][256][257]
Religious and conservative groups
Opposition due to the safety of the vaccine has been addressed through studies, but there is still some opposition focused on the sexual implications of the vaccine. Conservative[258][who?] groups in the US have opposed the concept of making HPV vaccination mandatory for pre-adolescent girls, claiming that making the vaccine mandatory is a violation of parental rights and that it will give a false sense of immunity to sexually transmitted infection, leading to early sexual activity. (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.[259][260][261][262] Parents also express confusion over recent mandates for entry to public school, pointing out that HPV is transmitted through sexual contact, not through attending school with other children.[263]
Conservative groups are concerned children will see the vaccine as a safeguard against STIs and will have sex sooner than they would without the vaccine while failing to use contraceptives.[263] However, the American Academy of Pediatrics disagreed with the argument that the vaccine increases sexual activity among teens.[264] 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."[265][266] A 2018 study of college-aged students found that HPV vaccination did not increase sexual activity.[267][unreliable medical source]
Parental opposition
Many parents opposed to providing the HPV vaccine to their pre-teens agree the vaccine is safe and effective, but find talking to their children about sex uncomfortable. Elizabeth Lange, of Waterman Pediatrics in Providence, RI, addresses this concern by emphasizing what the vaccine is doing for the child. Lange suggests parents should focus on the cancer prevention aspect without being distracted by words like 'sexually transmitted'. Everyone wants cancer prevention, yet here parents are denying their children a form of protection due to the nature of the cancer—Lange suggests that this much controversy would not surround a breast cancer or colon cancer vaccine. The HPV vaccine is suggested for 11-year-olds because it should be administered before possible exposure to HPV, but also because the immune system has the highest response for creating antibodies around this age. Lange also emphasized the studies showing that the HPV vaccine does not cause children to be more promiscuous than they would be without the vaccine.[263]
Controversy over the HPV vaccine remains present in the media. Parents in Rhode Island have created a Facebook group called "Rhode Islanders Against Mandated HPV Vaccinations" in response to Rhode Island's mandate that males and females entering the 7th grade, as of September 2015, be vaccinated for HPV before attending public school.[128][263]
Physician impact
The effectiveness of a physician's recommendation for the HPV vaccine also contributes to low vaccination rates and controversy surrounding the vaccine. A 2015 study of national physician communication and support for the HPV vaccine found physicians routinely recommend HPV vaccines less strongly than they recommend Tdap or meningitis vaccines, find the discussion about HPV to be long and burdensome, and discuss the HPV vaccine last, after all other vaccines. Researchers suggest these factors discourage patients and parents from setting up timely HPV vaccines. To increase vaccination rates, this issue must be addressed and physicians should be better trained to handle discussing the importance of the HPV vaccine with patients and their families.[268]
Ethics
Some researchers have compared the need for adolescent HPV vaccination to that of other childhood diseases such as chicken pox, measles, and mumps. This is because vaccination before infection decreases the risk of several forms of cancer.[269][270]
There has been some controversy around the HPV vaccine's rollout and distribution. Countries have taken different routes based on economics and social climate leading to issues of forced vaccination and marginalization of segments of the population in some cases.[271]
The rollout of a country's vaccination program is more divisive, compared to the act of providing vaccination against HPV. In more affluent countries, arguments have been made for publicly funded programs aimed at vaccinating all adolescents voluntarily. These arguments are supported by World Health Organization (WHO) surveys showing the effectiveness of cervical cancer prevention with HPV vaccination.[271]
In developing countries, the cost of the vaccine, dosing schedule, and other factors have led to suboptimal levels of vaccination. Future research is focused on low-cost generics and single-dose vaccination in efforts to make the vaccine more accessible.[272]
Research
There are high-risk HPV types that are not affected by available vaccines.[48] 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.[273] Efforts for this have included boosting the immunogenicity of L2 by linking together short amino acid sequences of L2 from different oncogenic HPV types or by displaying L2 peptides on a more immunogenic carrier.[274][275] 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.[276]
Therapeutic vaccines
In addition to preventive vaccines, 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.[277]
There is a working therapeutic HPV vaccine. It has gone through three clinical trials. The vaccine is officially called the MEL-1 vaccine but also known as the MVA-E2 vaccine. In a study it has been suggested that an immunogenic peptide pool containing epitopes that can be effective against all the high-risk HPV strains circulating globally and 14 conserved immunogenic peptide fragments from four early proteins (E1, E2, E6 and E7) of 16 high-risk HPV types providing CD8+ responses.[278][279][280][281]
Therapeutic DNA vaccine VGX-3100, which consists of plasmids pGX3001 and pGX3002, has been granted a waiver by the European Medicines Agency for pediatric treatment of squamous intraepithelial lesions of the cervix caused by HPV types 16 and 18.[282] According to an article published 16 September 2015 in The Lancet, which reviewed the safety, efficacy, and immunogenicity of VGX-3100 in a double-blind, randomized controlled trial (phase 2b) targeting HPV-16 and HPV-18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3, it is the first therapeutic vaccine to show efficacy against CIN 2/3 associated with HPV-16 and HPV-18.[283] In June 2017, VGX-3100 entered a phase III clinical trial called REVEAL-1 for the treatment of HPV-induced high-grade squamous intraepithelial lesions.[284] The estimated completion time for collecting primary clinical endpoint data is August 2019.[285]
As of October 2020, there are multiple therapeutic HPV vaccines in active development and in clinical trials, based on diverse vaccine platforms (protein-based, viral vector, bacterial vector, lipid encapsulated mRNA).[286]
Awards
In 2009, as part of the Q150 celebrations, the cervical cancer vaccine was announced as one of the Q150 Icons of Queensland for its role in "innovation and invention".[287]
Cervical cancer is a cancer arising from the cervix or in any layer of the wall of the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.
Human papillomavirus infection is caused by a DNA virus from the Papillomaviridae family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV, and two strains – HPV16 and HPV18 – account for 70% of all cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis.
Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They may be flat or project out from the surface of the skin, and their color may vary; brownish, white, pale yellow, pinkish-red, or gray. There may be a few individual warts or several, either in a cluster or merged together to look cauliflower-shaped. They can be itchy and feel burning. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection.
Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A change in bowel movements may also occur.
Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.
A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence. A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or reduce the effects of infection by any natural or "wild" pathogen. Vaccines go through multiple phases of trials to ensure safety and effectiveness.
Ian Hector Frazer is a Scottish-born Australian immunologist, the founding CEO and Director of Research of the Translational Research Institute (Australia). Frazer and Jian Zhou developed and patented the basic technology behind the HPV vaccine against cervical cancer at the University of Queensland. Researchers at the National Cancer Institute, Georgetown University, and University of Rochester also contributed to the further development of the cervical cancer vaccine in parallel.
Gardasil is an HPV vaccine for use in the prevention of certain strains of human papillomavirus (HPV). It was developed by Merck & Co. High-risk human papilloma virus (hr-HPV) genital infection is the most common sexually transmitted infection among women. The HPV strains that Gardasil protects against are sexually transmitted, specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal, and penile cancer cases. HPV types 6 and 11 cause an estimated 90% of genital warts cases. HPV type 16 is responsible for almost 90% of HPV-positive oropharyngeal cancers, and the prevalence is higher in males than females. Though Gardasil does not treat existing infection, vaccination is still recommended for HPV-positive individuals, as it may protect against one or more different strains of the disease.
Bovine papillomaviruses (BPV) are a paraphyletic group of DNA viruses of the subfamily Firstpapillomavirinae of Papillomaviridae that are common in cattle. All BPVs have a circular double-stranded DNA genome. Infection causes warts of the skin and alimentary tract, and more rarely cancers of the alimentary tract and urinary bladder. They are also thought to cause the skin tumour equine sarcoid in horses and donkeys.
Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).
Margaret Anne Stanley, OBE FMedSc, is a British virologist and epithelial biologist. She attended the Universities of London, Bristol, and Adelaide. As of 2018, she is an Emeritus Professor of Epithelial Biology in the Department of Pathology at the University of Cambridge and a Fellow of the Academy of Medical Sciences. She is also an Honorary Fellow of the UK Royal College of Obstetricians and Gynaecologists and an honorary fellow of Christ's College, Cambridge. Stanley is a research scientist in virology focusing on the human papillomavirus (HPV). Her research work has led to new scientific findings on HPV. Additionally, she uses her expertise on HPV to serve on multiple advisory committees and journal editorial boards.
HspE7 is an investigational therapeutic vaccine candidate being developed by Nventa Biopharmaceuticals for the treatment of precancerous and cancerous lesions caused by the human papillomavirus (HPV). HspE7 uses recombinant DNA technology to covalently fuse a heat shock protein (Hsp) to a target antigen, thereby stimulating cellular immune system responses to specific diseases. HspE7 is a patented construct consisting of the HPV Type 16 E7 protein and heat shock protein 65 (Hsp65) and is currently the only candidate using Hsp technology to target the over 20 million Americans already infected with HPV.
Measles vaccine protects against becoming infected with measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When the rate of vaccination within a population is greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if the rate of vaccination decreases. The vaccine's effectiveness lasts many years. It is unclear if it becomes less effective over time. The vaccine may also protect against measles if given within a couple of days after exposure to measles.
Rubella vaccine is a vaccine used to prevent rubella. Effectiveness begins about two weeks after a single dose and around 95% of people become immune. Countries with high rates of immunization no longer see cases of rubella or congenital rubella syndrome. When there is a low level of childhood immunization in a population it is possible for rates of congenital rubella to increase as more women make it to child-bearing age without either vaccination or exposure to the disease. Therefore, it is important for more than 80% of people to be vaccinated. By introducing rubella containing vaccines, rubella has been eradicated in 81 nations, as of mid-2020.
A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.
Jian Zhou was a Chinese virologist and cancer researcher, who with fellow researcher Ian Frazer, invented Gardasil and Cervarix, the vaccines for stimulating human immunological resistance to the cervical cancer-inducing human papilloma virus.
Diane Medved Harper is a United States professor in the Department of Family Medicine at the University of Michigan. Her area of expertise is human papillomavirus (HPV) and the diseases associated with it, as well as colposcopy, and she was one of the investigators in the clinical trials of Gardasil and Cervarix, vaccines against HPV.
Human papillomavirus (HPV)-associated oropharyngeal cancer awareness and prevention is a vital concept from a public and community health perspective.
The HPV Prevention and Control Board, founded in 2015, is an independent group of international experts supported by unrestricted grants from the pharmaceutical industry that bring together key professionals, groups and government officials to deal with issues related to screening and prevention programmes for human papillomavirus (HPV) infection, the persistence of which may lead to cervical cancer, the second most common cancer in women living in low-resource settings. The Board focusses on preventing cervical cancer in these countries by promoting the sharing of information on cervical screening and HPV vaccination, which by 2014 had reached only around 3% of eligible girls in low income countries.
Human Papillomavirus in Ghana; each year about 3,000 Ghanaian women are diagnosed cervical cancer caused by Human Papillomavirus, HPV. It is estimated that 2,000 women die out of the 3000 annually.
↑ "Gardasil 9 EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 6 April 2020. Retrieved 3 April 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
↑ "Gardasil EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 11 June 2022. Retrieved 6 July 2022.
↑ "Cervarix EPAR". European Medicines Agency (EMA). 20 September 2007. Retrieved 1 October 2024.
↑ World Health Organization (May 2011). The immunological basis for immunization series: module 19: human papillomavirus infection. World Health Organization. hdl:10665/44604. ISBN9789241501590.
1 2 World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
↑ Cox B, Sneyd MJ (2018). "HPV screening, invasive cervical cancer and screening policy in Australia". Journal of the American Society of Cytopathology. 7 (6): 292–299. doi:10.1016/j.jasc.2018.07.003. PMID31043298. S2CID58548623.
↑ Chow EP, Read TR, Wigan R, Donovan B, Chen MY, Bradshaw CS, etal. (May 2015). "Ongoing decline in genital warts among young heterosexuals 7 years after the Australian human papillomavirus (HPV) vaccination programme". Sexually Transmitted Infections. 91 (3): 214–219. doi:10.1136/sextrans-2014-051813. PMID25305210. S2CID24549759.
↑ Chow EP, Tabrizi SN, Fairley CK, Wigan R, Machalek DA, Garland SM, etal. (October 2021). "Prevalence of human papillomavirus in young men who have sex with men after the implementation of gender-neutral HPV vaccination: a repeated cross-sectional study". The Lancet. Infectious Diseases. 21 (10): 1448–1457. doi:10.1016/S1473-3099(20)30687-3. PMID34043963. S2CID235230838.
↑ Chow EP, Machalek DA, Tabrizi SN, Danielewski JA, Fehler G, Bradshaw CS, etal. (January 2017). "Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study". The Lancet. Infectious Diseases. 17 (1): 68–77. doi:10.1016/S1473-3099(16)30116-5. PMID27282422.
↑ Rosenthal E (19 August 2008). "Drug Makers' Push Leads to Cancer Vaccines' Fast Rise". The New York Times. Archived from the original on 9 April 2009. Retrieved 20 August 2008. Said Dr. Raffle, the British cervical cancer specialist: 'Oh, dear. If we give it to boys, then all pretense of scientific worth and cost analysis goes out the window.'
↑ Moi H, Iversen OE (17 December 2011). "Gi guttene jentevaksine". Dagens Næringsliv (in Norwegian). p.32. Zur Haussen, som fikk Nobelprisen i 2009 for sin HPV-forskning, har lenge argumentert for vaksinasjon av gutter, både som egen beskyttelse og beskyttelse av kvinner.
↑ Goss MA, Lievano F, Buchanan KM, Seminack MM, Cunningham ML, Dana A (June 2015). "Final report on exposure during pregnancy from a pregnancy registry for quadrivalent human papillomavirus vaccine". Vaccine. 33 (29): 3422–3428. doi:10.1016/j.vaccine.2015.04.014. PMID25869893.
↑ McNeil C (April 2006). "Who invented the VLP cervical cancer vaccines?". Journal of the National Cancer Institute. 98 (7): 433. doi:10.1093/jnci/djj144. PMID16595773.
↑ U.S. patent 7,476,389, titled "Papilloma Virus Vaccines", was granted to co-inventors Ian Frazer and Jian Zhou (Zhou posthumously) on 13 January 2009. Its US application was filed on 19 January 1994 but claimed priority under a 20 July 1992, PTC filing to the date of an initial [AU] Australian patent application filed on 19 July 1991.
↑ Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, etal. (November 2004). "Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial". Lancet. 364 (9447): 1757–1765. doi:10.1016/S0140-6736(04)17398-4. PMID15541448.
↑ Fesenfeld M, Hutubessy R, Jit M (August 2013). "Cost-effectiveness of human papillomavirus vaccination in low and middle-income countries: a systematic review". Vaccine. 31 (37): 3786–3804. doi:10.1016/j.vaccine.2013.06.060. PMID23830973.
↑ Botha MH, Dochez C (September 2012). "Introducing human papillomavirus vaccines into the health system in South Africa". Vaccine. 30 (Suppl 3): C28–C34. doi:10.1016/j.vaccine.2012.03.032. PMID22939017.
1 2 3 Tabrizi S. Brotherton J. Kaldor J et al. Fall in Human Papillomavirus Prevalence Following a National Vaccination Program. Journal of Infectious Diseases. 24 October 2012.
↑ Tabrizi SN, Brotherton JM, Kaldor JM, Skinner SR, Liu B, Bateson D, etal. (October 2014). "Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study". The Lancet. Infectious Diseases. 14 (10): 958–966. doi:10.1016/S1473-3099(14)70841-2. PMID25107680.
↑ "Vaccination programmes". Folkhälsomyndigheten. The Public Health Agency of Sweden. 18 February 2022. Archived from the original on 12 July 2022. Retrieved 26 November 2022.
↑ "HPV ワクチンの接種状況に関する検討"[HPV Consideration of HPV vaccination status](PDF). Ministry of Health, Labour and Welfare of Japan. 26 June 2024. Archived(PDF) from the original on 5 February 2024. Retrieved 20 February 2024.
↑ Al-Sabai W (15 September 2018). "قرار وزاري بإلزامية تطعيم سرطان عنق الرحم"[A ministerial decision mandating cervical cancer vaccination]. Emarat Alyoum (in Arabic). Archived from the original on 15 September 2018. Retrieved 16 September 2018.
↑ Moghtaderi A, Adams S (June 2016). "The Role of Physician Recommendations and Public Policy in Human Papillomavirus Vaccinations". Applied Health Economics and Health Policy. 14 (3): 349–359. doi:10.1007/s40258-016-0225-6. PMID26873090. S2CID25655517.
↑ Budhwani H, De P (December 2017). "Human papillomavirus vaccine initiation in Asian Indians and Asian subpopulations: a case for examining disaggregated data in public health research". Public Health. 153: 111–117. doi:10.1016/j.puhe.2017.07.036. PMID29028565.
↑ De P, Budhwani H (March 2017). "Human papillomavirus (HPV) vaccine initiation in minority Americans". Public Health. 144: 86–91. doi:10.1016/j.puhe.2016.11.005. PMID28274389.
1 2 Smith MJ (December 2015). "Promoting Vaccine Confidence". Infectious Disease Clinics of North America (Review). 29 (4): 759–769. doi:10.1016/j.idc.2015.07.004. PMID26337737.
↑ Reno JE, Dempsey AF (February 2022). "Promoting HPV vaccination among Latinx: an application of the extended parallel processing model". Journal of Behavioral Medicine. 46 (1–2): 324–334. doi:10.1007/s10865-022-00293-7. PMID35178652. S2CID246905792.
1 2 Malmqvist E, Helgesson G, Lehtinen J, Natunen K, Lehtinen M (February 2011). "The ethics of implementing human papillomavirus vaccination in developed countries". Medicine, Health Care and Philosophy. 14 (1): 19–27. doi:10.1007/s11019-010-9285-9. PMID20853152. S2CID27444545.
↑ van Driel WJ, Ressing ME, Brandt RM, Toes RE, Fleuren GJ, Trimbos JB, etal. (December 1996). "The current status of therapeutic HPV vaccine". Annals of Medicine. 28 (6): 471–477. doi:10.3109/07853899608999110. PMID9017105.
↑ Albarran Y, Carvajal A, de la Garza A, Cruz Quiroz BJ, Vazquez Zea E, Díaz Estrada I, etal. (2007). "MVA E2 recombinant vaccine in the treatment of human papillomavirus infection in men presenting intraurethral flat condyloma: a phase I/II study". BioDrugs. 21 (1): 47–59. doi:10.2165/00063030-200721010-00006. PMID17263589. S2CID26415621.
↑ Corona Gutierrez CM, Tinoco A, Navarro T, Contreras ML, Cortes RR, Calzado P, etal. (May 2004). "Therapeutic vaccination with MVA E2 can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus". Human Gene Therapy. 15 (5): 421–431. doi:10.1089/10430340460745757. PMID15144573.
World Health Organization (2011). The immunological basis for immunization series: module 19: human papillomavirus infection. World Health Organization (WHO). hdl:10665/44604. ISBN9789241501590.
World Health Organization (2016). Scaling-up HPV vaccine introduction. World Health Organization (WHO). hdl:10665/251909. ISBN9789241511544.
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