HPV Vaccine: Who Should Get It and When

What Is the HPV Vaccine?

The HPV vaccine is a preventive vaccine that protects against infection with human papillomavirus (HPV) strains responsible for cervical cancer, other HPV-related cancers, and genital warts. The currently available HPV vaccine in the United States is Gardasil 9, a 9-valent (nine-strain) vaccine manufactured by Merck. It is one of the most successful examples of cancer prevention through vaccination in medical history: by preventing HPV infection with the strains that cause approximately 90% of HPV-related cancers, Gardasil 9 has the potential to dramatically reduce the global burden of cervical, anal, oropharyngeal, penile, vaginal, and vulvar cancers.

The development of the HPV vaccine was possible because researchers identified that HPV causes virtually all cervical cancers and that protection against HPV infection could be achieved through vaccination. The first HPV vaccines — the bivalent Cervarix (HPV 16/18) and the quadrivalent Gardasil (HPV 6/11/16/18) — were approved by the FDA in the mid-2000s. Gardasil 9, the current and far more comprehensive 9-valent formulation, was approved by the FDA in December 2014 and has been the only HPV vaccine distributed in the United States since 2017. Cervarix was withdrawn from the US market in 2016.

Understanding who should receive the HPV vaccine, at what ages, on what schedule, and with what expectations for efficacy and safety helps individuals and parents make informed decisions about one of the most impactful cancer-prevention tools available.

Which HPV Types Does Gardasil 9 Cover?

Gardasil 9 protects against nine HPV types:

• HPV 16 and 18: The two most oncogenic HPV strains, responsible for approximately 70% of cervical cancers, the majority of anal cancers, and a large proportion of vulvar, vaginal, penile, and oropharyngeal cancers.
• HPV 31, 33, 45, 52, and 58: Five additional high-risk oncogenic types together responsible for approximately 15–20% of cervical cancers. Including these five types expands cervical cancer protection from approximately 70% (with the original quadrivalent vaccine covering only HPV 16/18) to approximately 90%.
• HPV 6 and 11: Low-risk types that do not cause cancer but are responsible for approximately 90% of genital warts (condyloma acuminata). While genital warts are not life-threatening, they are a significant source of morbidity, discomfort, stigma, and healthcare costs; their prevention is an important benefit of the 9-valent formulation.

Together, the nine types covered by Gardasil 9 are responsible for approximately 90% of HPV-related cancers and nearly all genital warts. No currently available HPV vaccine covers all 14 high-risk HPV types, which is why vaccinated women still require routine cervical cancer screening for the remaining high-risk types not included in the vaccine.

Who Should Get the HPV Vaccine

The Advisory Committee on Immunization Practices (ACIP), which sets US immunization recommendations, provides the following guidance on HPV vaccination:

Routine vaccination (ages 11–12): The HPV vaccine is recommended routinely for all children at age 11 or 12 years. Vaccination at this age is optimal for several reasons: the immune response to the vaccine is stronger at younger ages; the vaccine is most effective when given before first sexual exposure to HPV; and vaccinating in early adolescence ensures protection is in place before HPV exposure occurs. The series can be started as early as age 9, which is the FDA-approved minimum age.

Catch-up vaccination (ages 13–26): All individuals aged 13 through 26 years who were not adequately vaccinated at the recommended age should receive the HPV vaccine series as catch-up vaccination. ACIP recommends catch-up vaccination for everyone in this age group who has not completed the series. The vaccine still provides significant benefit in this age range, even in individuals who have already been sexually active, because it protects against HPV types not yet acquired.

Shared clinical decision-making (ages 27–45): For adults aged 27 through 45, HPV vaccination is not routinely recommended but may be considered through shared clinical decision-making. The potential benefit in this age group is lower than for younger individuals because many adults in this range have already been exposed to the HPV types covered by the vaccine. However, individuals in this age group who are at ongoing risk for new HPV infections — including those with new sexual partners — may still benefit from vaccination. Individuals in this age group should discuss the potential benefit with their healthcare provider.

Immunocompromised individuals: People with immunocompromising conditions (HIV infection, organ transplant, chronic immunosuppressive therapy) benefit from HPV vaccination through age 26 and should receive the 3-dose series regardless of age at initiation.

HPV Vaccine Dosing Schedule

The number of vaccine doses required depends on the age at which the first dose is given:

2-dose schedule (for series started before age 15):

• Dose 1: at the chosen start date
• Dose 2: 6–12 months after the first dose
• A minimum interval of 5 months is required between doses 1 and 2; if the second dose is given less than 5 months after the first, a third dose is required

3-dose schedule (for series started at age 15 or older, or for immunocompromised individuals):

• Dose 1: at the chosen start date
• Dose 2: 1–2 months after the first dose
• Dose 3: 6 months after the first dose (minimum 12 weeks after dose 2)

The reason younger adolescents can achieve adequate protection with only two doses is that the immune response to HPV vaccination is significantly stronger in children ages 9–14 than in older adolescents and adults — two doses in this younger age group generate antibody levels comparable to or higher than three doses in older individuals. The 2-dose schedule was approved by the FDA in 2016 after clinical trial data confirmed non-inferior immunogenicity.

How the HPV Vaccine Works

Gardasil 9 is a recombinant subunit vaccine based on virus-like particles (VLPs). VLPs are hollow, non-infectious particles composed of the L1 major capsid protein of each of the nine targeted HPV types. The L1 protein naturally self-assembles into a structure that closely resembles the outer shell of the actual HPV virus — which is why the immune system mounts a strong antibody response — but VLPs contain no viral DNA and cannot cause HPV infection or any HPV-related disease.

When the vaccine is administered, the immune system recognizes the L1 VLPs as foreign antigens and produces neutralizing antibodies against each of the nine targeted HPV types. These antibodies persist after vaccination and are present in the genital mucosa, where they can neutralize HPV virions at the time of sexual exposure before they can infect cervical basal epithelial cells. The vaccine generates durable immunological memory, and antibody levels have been shown to remain protective for at least 10–14 years in follow-up studies of originally vaccinated cohorts; the duration of protection is expected to extend well beyond this based on immunological modeling and the kinetics of vaccine-induced memory B cells.

Vaccine Efficacy: Clinical Trials and Real-World Evidence

The HPV vaccine’s efficacy has been established in large randomized controlled trials and confirmed by compelling real-world surveillance data from countries with established national HPV vaccination programs.

Clinical trial evidence: The pivotal FUTURE II trial of the original quadrivalent Gardasil vaccine in women ages 15–26 demonstrated approximately 98% efficacy against CIN 2/3 caused by HPV 16 or HPV 18 in the per-protocol efficacy population (women who were negative for the vaccine HPV types at enrollment and who completed all three doses). In the modified intention-to-treat population — which included women who had prior exposure to some vaccine HPV types, better reflecting the real-world scenario — efficacy was approximately 44–55%, illustrating that prior HPV exposure reduces but does not eliminate vaccine benefit. The FUTURE I trial showed similar efficacy against genital warts, vulvar intraepithelial neoplasia, and vaginal intraepithelial neoplasia. Subsequent trials of Gardasil 9 demonstrated non-inferior immunogenicity to the quadrivalent vaccine for HPV 6/11/16/18 and additional high efficacy (~96%) against the five additional types (31/33/45/52/58).

Real-world evidence — Australia: Australia launched one of the world’s first national school-based HPV vaccination programs in 2007, targeting girls aged 12–13 (with catch-up vaccination for older girls and later extended to boys). By 2015 — just eight years after vaccination began — the incidence of genital warts in young heterosexual women and men had decreased by over 90% in Australia’s states with high vaccination coverage, demonstrating herd immunity. CIN 2+ lesions in women under 25 have declined by approximately 75–85% in vaccinated cohorts. Australia is now projecting that it may be the first country in the world to achieve cervical cancer elimination (defined as fewer than 4 cases per 100,000 women) within the coming decades.

Real-world evidence — United Kingdom and Scandinavia: UK and Nordic countries with high adolescent vaccination coverage have reported 40–90% reductions in CIN 2/3 incidence in vaccinated cohorts, with the largest reductions in those vaccinated at the youngest ages. A landmark 2020 study in The New England Journal of Medicine analyzing Swedish national data found a 63% lower risk of invasive cervical cancer in women vaccinated before age 17, compared to unvaccinated women — the first large-scale real-world evidence of a reduction in invasive cervical cancer, not just pre-cancerous lesions, following HPV vaccination.

Safety Profile

Gardasil 9 has been extensively studied in clinical trials involving tens of thousands of participants, and more than 270 million doses have been distributed worldwide as of 2023. The vaccine’s safety profile is well-characterized:

Common side effects (mild to moderate, resolving within 1–3 days):

• Injection site pain: reported in approximately 80–90% of vaccine recipients
• Injection site swelling: approximately 25–40%
• Injection site redness: approximately 30–40%
• Headache: approximately 10–15%
• Fatigue: approximately 10–15%
• Fever: less than 10%

Syncope (fainting): Brief fainting can occur after any vaccine injection, particularly in adolescents. Healthcare providers administer the vaccine with the recipient seated and recommend a 15-minute observation period after injection, with the recipient remaining seated or lying down to prevent injury from fainting-related falls.

Serious adverse events: Large-scale post-marketing surveillance through the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink (VSD), and international pharmacovigilance programs have not identified any causally associated serious adverse events related to HPV vaccination. Initial concerns about anaphylaxis, postural orthostatic tachycardia syndrome (POTS), complex regional pain syndrome (CRPS), and premature ovarian insufficiency (POI) have been extensively investigated; systematic reviews have not found causal evidence linking these conditions to HPV vaccination.

Contraindications: Gardasil 9 should not be given to individuals with a history of severe allergic reaction (anaphylaxis) to a previous dose of the vaccine or to any vaccine component, including yeast (the L1 proteins are produced in Saccharomyces cerevisiae). The vaccine is not recommended during pregnancy, though inadvertent vaccination during early pregnancy is not a reason for pregnancy termination; no adverse pregnancy outcomes have been observed in women who received HPV vaccine before realizing they were pregnant.

HPV Vaccine for Males

The HPV vaccine is recommended for males on the same schedule as females. While the public conversation about HPV vaccination has historically focused on cervical cancer prevention in females, males benefit substantially from HPV vaccination for multiple reasons:

• Anal cancer: HPV 16 and 18 cause approximately 90% of anal cancers. Anal cancer incidence has been rising in the United States. The HPV vaccine is highly effective at preventing HPV 16/18 infection and associated anal intraepithelial neoplasia (AIN) in males.
• Oropharyngeal cancer: HPV 16 is responsible for approximately 70% of oropharyngeal (throat) cancers, and oropharyngeal cancer incidence — particularly in men — has been rising steadily. Vaccination before HPV 16 exposure prevents oropharyngeal HPV infection and its cancer consequences.
• Penile and other cancers: HPV causes penile cancer (approximately 50% attributable to HPV) and cancers of the scrotum, urethra, and anus.
• Genital warts: HPV 6 and 11 cause approximately 90% of genital warts. Vaccination prevents genital wart development in males, reducing significant morbidity.
• Herd protection: When males are vaccinated, they are less likely to transmit HPV to sexual partners, contributing to herd immunity effects that protect unvaccinated individuals (including those who cannot be vaccinated due to contraindications).

Frequently Asked Questions

Is it too late to get the HPV vaccine if I am already sexually active?

No — being sexually active does not preclude benefit from the HPV vaccine. Most sexually active adults have not been infected with all nine HPV types covered by Gardasil 9. Vaccination protects against the types not yet acquired, even if some types have already been encountered. The benefit decreases with age (because cumulative HPV exposure is higher in older adults), which is why ACIP recommends routine vaccination through age 26 and shared clinical decision-making for ages 27–45, but vaccination can still provide meaningful protection even after sexual debut.

Does the HPV vaccine contain live virus?

No. Gardasil 9 contains virus-like particles (VLPs) made from the L1 capsid protein of each HPV type. VLPs are hollow protein shells with no viral DNA inside. They cannot infect cells, replicate, or cause HPV infection of any kind. They stimulate an immune response because the immune system recognizes the protein shell as foreign, not because they behave like a real virus.

If I had a positive HPV test, should I still get the vaccine?

A positive HPV test result indicates infection with one or more high-risk HPV types, but it does not identify which specific types. Vaccination can still protect against the types in Gardasil 9 that you have not yet been infected with. ACIP does not recommend testing for HPV before vaccination — anyone in the recommended age groups should receive the vaccine regardless of prior HPV test results or known prior infection history.

Should my child get the HPV vaccine at age 11 or 12? Isn’t that too young?

The recommendation to vaccinate at ages 11–12 is based on the goal of ensuring protection is in place well before first sexual exposure to HPV, and on the evidence that immune responses are strongest when vaccination occurs in early adolescence. The HPV vaccine is not a sign that parents anticipate or condone sexual activity at young ages — it is the same rationale as hepatitis B vaccination given at birth (before any risk of exposure): vaccinating early ensures protection is present when it is eventually needed. The vaccine has been safety-tested in this age group and is among the most thoroughly studied vaccines in history.

HPV Vaccination and the Global Elimination of Cervical Cancer

The World Health Organization launched its Global Strategy to Accelerate the Elimination of Cervical Cancer in 2020, with a target of reducing incidence below 4 cases per 100,000 women in all countries. The strategy rests on three pillars: 90% of girls vaccinated with HPV vaccine by age 15; 70% of women screened with a high-performance test by age 35 and again by age 45; and 90% of women identified with cervical disease receiving treatment. If these targets are achieved globally by 2030 and maintained through 2120, modeling estimates that more than 74 million cervical cancers could be averted over the next century.

Countries that have made the greatest progress toward these targets — Australia, the United Kingdom, Sweden, Denmark — have achieved vaccination coverage rates of 80% or higher in adolescent girls and are already observing large reductions in cervical pre-cancer and early cervical cancer in vaccinated cohorts. Australia, with the world’s longest-running school-based HPV vaccination program (since 2007), is projected to become the first country to eliminate cervical cancer as a public health problem. The Australian experience provides a proof of concept for what is achievable globally with high vaccination coverage combined with effective cervical cancer screening programs.

The HPV vaccine is approved by the US Food and Drug Administration and recommended by the Centers for Disease Control and Prevention for all children at age 11 or 12, with catch-up vaccination through age 26 and shared clinical decision-making for ages 27 to 45. For the latest evidence-based cervical cancer screening recommendations that remain important even for vaccinated individuals, see our comprehensive guide to cervical cancer screening.

HPV vaccination is among the clearest examples in medicine of prevention being more effective and less costly than treatment. The lifetime cost of treating cervical cancer — including surgery, radiation, chemotherapy, and supportive care — is vastly greater than the cost of a two- or three-dose vaccination series. Beyond cervical cancer, HPV vaccination prevents anal cancers, oropharyngeal cancers, genital warts, and other HPV-related disease across all genders. Economic analyses consistently show that HPV vaccination is cost-effective or even cost-saving at the population level when high coverage rates are achieved. Ensuring that children receive the recommended HPV vaccine series — ideally at ages 11 or 12, before first sexual exposure to HPV — is one of the most impactful investments parents and healthcare providers can make in a young person’s long-term cancer risk. For adults who missed vaccination in adolescence, the window through age 26 provides another opportunity for meaningful benefit. Learn more about how HPV causes cervical cancer and why prevention matters at our guide to HPV and cervical cancer, and learn about what to expect from cervical screening in our article on the Pap smear.