HPV vaccine

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. Not much is known about the efficacy and protective duration of the simplified schedule in boys and men. == Background ==

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 (Women Living With HIV), 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 40 per 100 000 in some countries of sub-Saharan Africa. 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 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. 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. She has also encouraged women to continue pap screening after they are vaccinated and to be aware of potential adverse effects. ==Medical uses==

HPV vaccines are used to prevent HPV infection and therefore in particular cervical cancer. The vaccines require three doses for those ages 15 and above. 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. Since the vaccines only cover some high-risk types of HPV, cervical cancer screening is recommended even after vaccination. In the US, the recommendation is for women to receive routine Pap smears beginning at age 21. In Australia, the national screening program has changed from the two yearly cytology (pap smears) to being based on tests for HPV DNA, based on work by Karen Canfell and others. As of 2021, the World Health Organization recommends HPV DNA testing as the preferred screening method. 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. However, other high-risk HPV types are not affected by the vaccine. and more than nine years for Cervarix. As of September 2024, 57 countries are implementing the single-dose schedule. 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. A single dose might be effective. 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. 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. Neither Cervarix nor Gardasil prevent other sexually transmitted infections, and they do not treat existing HPV infections or cervical cancer. Gardasil When Gardasil was first introduced, it was recommended as a prevention for cervical cancer for women 25 years old or younger. 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. Males As of 2022, 47 countries (24% of WHO member states) have introduced HPV vaccine in their national immunization programme for boys. 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. 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. From a public health point of view, vaccinating men as well as women (GNV, or Gender Neutral Vaccination) decreases the virus pool within the population. Whether this is cost-effective depends on a number of assumptions: (a) cost of the vaccine, (b) assumed duration of immunity, (c) whether diseases other than cervical cancer are considered, and (d) the assumed discount rate, for the cost of a vaccine is current but the cost of disease avoided is in the far future. A literature review in 2025 == Recommendations from authorities ==

Introduction of HPV vaccination for boys by country Australia Australia introduced HPV vaccination for boys in 2013. Ireland Ireland introduced HPV vaccination for boys aged 13 as part of their National Immunization Plan in 2019. UK UK introduced HPV vaccination for boys aged 12 as part of their National Immunization Plan in 2019. Portugal Portugal introduced universal HPV vaccination for boys aged 10 years and above as part of its National Immunization Plan in 2020. Japan In October 2025, a coalition of 32 academic societies—including the Japan Pediatric Society, the Japanese Society of Obstetrics and Gynaecology, and the Japanese Association of Infectious Diseases—submitted a formal request to the Ministry of Health, Labour and Welfare calling for the introduction of routine HPV vaccination for males. Despite this, the ministry's advisory subcommittee has twice raised concerns over cost-effectiveness, in March 2024 and September 2025, and as of late 2025 routine vaccination for males has not been approved. 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. Soon after that, the vaccine was approved by the FDA for use in males aged 9 to 26 for prevention of genital warts In 2011, an advisory panel for the US Centers for Disease Control and Prevention (CDC) recommended the vaccine for boys ages 11–12. 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. For those under the age of 27 who have not been fully vaccinated the CDC recommends vaccination. 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. World Health Organization (WHO) The HPV vaccine is on the WHO Model List of Essential Medicines. The WHO recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures. 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. The WHO has a global strategy for cervical cancer elimination. Its first pillar is having 90% of girls fully vaccinated with the HPV vaccine by 15 years of age. The WHO-recommended primary target population for HPV vaccination is girls aged 9–14 years before they become sexually active. Females aged ≥15 years, boys, older males or MSM are secondary target populations. Cervical cancer screening is still required following vaccination. == Side effects ==

HPV vaccines are safe and well tolerated and can be used in persons who are immunocompromised or HIV-infected. Pain at the site of injection occurs in between 35% and 88% of people When comparing the HPV vaccine to a placebo (control) vaccine taken by women, there is no difference in the risk of severe adverse events. There have been 22,000 Vaccine Adverse Event Reporting System (VAERS) reports following the vaccination. , in the US there were 44 reports of death in females after receiving the vaccine. , the CDC continued to recommend Gardasil vaccination for the prevention of four types of HPV. 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. Contraindications While the use of HPV vaccines can help reduce cervical cancer deaths by two-thirds around the world, not everyone is eligible for vaccination. Some factors exclude people from receiving HPV vaccines. These factors include: • People 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. • 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. 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. However, the clinical trials had a relatively small sample size. , the vaccine is not recommended for pregnant women. 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. ==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 225 μg of aluminum, 9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 μg of polysorbate 80, 35 μg of sodium borate, and water. The combination of ingredients totals 0.5 mL. HPV types 16 and 18 cause about 70% of all cervical cancer. Gardasil also targets HPV types 6 and 11, which together 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 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. 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. 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. 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. As a result, the University of Queensland receives royalty payments from the sale of these vaccines even today. By the early 2000s, developers, convinced of the market of the vaccine, had begun refining, researching, and trialing L1-based HPV vaccines. 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, 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. Cervarix was approved for use in the US in October 2009. Harald zur Hausen was awarded half of the $1.4 million Nobel Prize in Medicine in 2008 for his work showing that cervical cancer is caused by certain types of HPVs. 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. 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). ==Society and culture==

Economics , 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. 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 (GNV, or Gender Neutral Vaccination) decreases the virus pool within the population. Whether this is cost-effective depends on a number of assumptions: (a) cost of the vaccine, (b) assumed duration of immunity, (c) whether diseases other than cervical cancer are considered, and (d) the assumed discount rate, for the cost of a vaccine is current but the cost of disease avoided is in the far future. A literature review in 2025 looked at studies of this questions. A majority of the studies concluded GNV was cost-effective, except perhaps in countries such as Great Britain and New Zealand that had very high female coverage. 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. Brand names The vaccine is sold under various brand names including Gardasil, Cervarix, Cecolin, Vaccine implementation The primary target group in most of the countries recommending HPV vaccination is young adolescent girls, aged 9–14. 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. School-entry vaccination requirements were found to increase the use of the HPV vaccine. Algeria No Angola No 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 became 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. United Republic of Tanzania Yes (GAVI support in 2013) 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 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. 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. 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. In 2012, the Australian Government announced it would be extending the National HPV Vaccination Program to include males, through the National Immunisation Program Schedule. Updated results were reported in 2014. 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, and February 2010 for use in males. The vaccines Cervarix, Gardasil, and Gardasil 9 are authorized for use in Canada, with Gardasil 9 the primary vaccine used. 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+. 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). Cervarix is registered in China for girls aged 9 to 45, adopting 3-dose program within 6 months. Cervarix was launched in China in 2017, and it was the first approved HPV vaccine in China. China has since developed two HPV vaccines of its own: Cecolin (licensed in China in 2019) and Walrinvax (licensed in China in 2022). Colombia The vaccine was introduced in 2012. 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. Costa Rica Since June 2019, the vaccine has been administered compulsorily by the state, free of charge to girls at ten years of age. Europe As of 2020, the European Centre for Disease Prevention and Control (ECDC) reports that the vaccine uptake among females is the following: 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. India HPV vaccine (both Gardasil and Cervarix) was introduced in Indian markets in 2008, and has been included in 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. HPV vaccination has been recommended by the National Technical Advisory Group on Immunization, but has not been implemented in India as of 2018. 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. 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). In 2026, the Government of India launched a nationwide vaccination campaign for girls aged 14. 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. The programme was expanded to include males in 2019. 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. 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. 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 €11.66 million over the next five years. Uptake is low for several reasons: among them is that cervical cancer is rare in Israel, cost when not covered by insurance, and religious concerns. Japan The quadrivalent vaccine has been approved for males and the 9-valent one for females. Since 2010, young women in Japan have been eligible to receive the cervical cancer vaccination for free. 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. 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." 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. Over an overlapping time period (2009–2019), the age-adjusted mortality rate from cervical cancer increased by 9.6%. 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. 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. 225,993 girls were vaccinated for the first round of routine vaccination in 2022, and the vaccination rate was 42.2%. 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. Laos In 2013, Laos began implementation of the HPV vaccine, with the assistance of Gavi, the Vaccine Alliance. 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. 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. 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. In 2011 Mexico approved a nationwide use of HPV vaccination program to include vaccination of all 9-year-old girls. 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. 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. 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. 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. 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, and according to Abu Dhabi Health Authority, the cancer is also the seventh highest cause of death of women in the U.A.E. 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. Moreover, starting 1 June 2013, the vaccine was offered free of charge for women between the ages of 18 and 26, in Abu Dhabi. 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. The vaccine is to be administers to all school girls in the 8th grade girls, aged 13. 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. 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. 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. 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. 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. 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. Cervarix was the HPV vaccine offered from its introduction in September 2008, to August 2012, with Gardasil being offered from September 2012. The change was motivated by Gardasil's added protection against genital warts. United States Adoption On 30 August 2021, fifteen leading academic and freestanding cancer centers with membership in the Association of American Cancer Institutes (AACI), all National Cancer Institute (NCI)-designated cancer centers, the American Cancer Society, the American Society of Clinical Oncology, the American Association for Cancer Research, and the St. Jude Children's Research Hospital have issued a joint statement urging the US health care systems, physicians, parents, children, and young adults to get HPV vaccination and other recommended vaccinations back on track during the National Immunization Awareness Month. , the proportion of such females receiving an HPV vaccination had risen to 38%. The government began recommending vaccination for boys in 2011; , the vaccination rate among boys (at least one dose) had reached 35%. 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. 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. 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). Legislation Four states have laws that require HPV vaccination for school students: 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. Shortly after the first HPV vaccine was approved, bills to make the vaccine 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. 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. 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. 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. 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. The Centers for Disease Control and Prevention repealed all HPV vaccination directives for immigrants effective 14 December 2009. Uptake in the United States appears to vary by ethnicity and whether someone was born outside the United States. 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. 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. 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 people 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. provides Cervarix free of charge 1-877-VACC-911 to low-income women, ages 19 to 25, who do not have insurance. Merck's Vaccine Patient Assistance Program 1-800-293-3881 provides Gardasil free to low-income women and men, ages 19 to 26, who do not have insurance, including immigrants who are legal residents. Opposition in the United States 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. 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. Insurance companies In 2007, there was significant opposition from health insurance companies to covering the cost of the vaccine ($360). , the estimated cost in the United States is $257/dose, largely covered by insurance. 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 groups in the US, such as Focus on the Family, 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. 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. 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. 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." A 2018 study of college-aged students found that HPV vaccination did not increase sexual activity. 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. 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. 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. 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. ==Research==

There are high-risk HPV types that are not affected by available vaccines. 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. 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. After exposure Although HPV vaccination is most encouraged before any exposure to the target strains, its use is still beneficial in women who have contracted some of the target types because it's unlikely for a person to have been exposed to all target types. According to a 2008 article by the editor-in-chief of ''Harvard Women's Health Watch'', the quadrivalent vaccine is able to reduce the occurrence of warts and precancerous lesions in HPV-positive women, and also appeared to reduce the chance of infection by non-targeted types. A 2023 review article finds that vaccination reduces the chance of further HPV-associated diseases even in those already showing HPV-related precancers and diseases. At this point the standard vaccine is not believed to be therapeutic, so this effect is attributed to the vaccine preventing the establishment of new infections. 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. 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. 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. 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. 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. The estimated completion time for collecting primary clinical endpoint data is August 2019. 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). 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". In 2017, National Cancer Institute scientists Douglas R. Lowy and John T. Schiller received the Lasker-DeBakey Clinical Medical Research Award for their contributions leading to the development of HPV vaccines. == References ==