The Current Landscape of HPV Cancers and HPV Vaccination

Human papillomaviruses (HPV) cause nearly 630,000 cases of cancer worldwide each year. The majority—530,000—are cervical cancers, but HPV also is responsible for about 100,000 cancers at five other sites, including the oropharynx, anus, penis, vulva, and vagina.1* In 2006, the first HPV vaccine was approved, making available a powerful new tool for preventing cancers and other diseases caused by these viruses. Two additional HPV vaccines were approved in 2009 and 2014. Despite extensive evidence that these vaccines are remarkably effective and safe, early uptake was slow in the United States and some other countries.

In its 2012-2013 report, Accelerating HPV Vaccine Uptake: Urgency for Action to Prevent Cancer, the President’s Cancer Panel concluded that underuse of HPV vaccines was a serious threat to progress against cancer and recommended several steps to increase vaccination in the United States and globally.2 Other high-profile reports—including 2015 and 2018 reports from the National Vaccine Advisory Committee 3,4 and 2016 reports from the Cancer Moonshot Blue Ribbon Panel5 and Cancer Moonshot Task Force6—echoed the Panel’s call for action.

This report of the Panel Chair provides an update on the landscape of HPV cancers and HPV vaccination. Substantial progress in HPV vaccine uptake has been achieved in recent years—the percentage of adolescents who started the HPV vaccine series increased an average of 5 percentage points each year between 2013 and 2017.7 This is a testament to the hard work and dedication of the many stakeholders who have come together to promote HPV vaccination. However, the United States and many other countries still fall far short of target vaccination rates.

HPV Cancers Affect Thousands of U.S. Women and Men

There are more than 150 strains, or types, of HPV. In the United States, about 79 million people currently are infected with HPV, and about 14 million will become newly infected with HPV each year. Most sexually active men and women will be infected with HPV at some point in their lives if they do not receive the HPV vaccine.8 The majority of HPV infections go away without treatment and do not cause health problems. In some cases, however, HPV infections persist and cause cancer and other diseases.

In the United States, HPV causes nearly 34,000 cases of cancer each year (Figure 1).9 In addition, about 300,000 U.S. women undergo invasive treatment for cervical precancers caused by HPV.10,11 Women are more likely than men to be diagnosed with HPV cancers, but the burden of HPV cancers among men is increasing. This trend is driven largely by increases in HPV-positive oropharyngeal cancers over the past three decades, particularly among men, even as incidence rates of other head and neck cancers and many other cancers are decreasing.12-15 The number of oropharyngeal cancers attributed to HPV is now higher than the number of cervical cancers in the United States.9,16

Figure 1

Numbers of U.S. Cancers Caused by HPV

Vaccines Protect Against Cancer-Causing HPV Types

When the 2012-2013 Panel report on HPV vaccination was released, two HPV vaccines were approved for use in the United States—Cervarix and Gardasil. Both vaccines are designed to protect against the two most common cancer-causing types of HPV—HPV 16 and HPV 18—which together account for about two-thirds of cervical cancers. Gardasil also protects against HPV 6 and 11, which cause genital warts and recurrent respiratory papillomatosis, a rare but debilitating disease characterized by noncancerous growths in the respiratory tract. Cervarix provides cross-protection against three additional cancer-causing HPV types (HPV 31, 33, and 45) that are related to HPV 16 or HPV 18.17

In 2014, the U.S. Food and Drug Administration (FDA) approved a third HPV vaccine—Gardasil 9—which protects against HPV 16, 18, 6, 11, and five additional cancer-causing HPV types (HPV 31, 33, 45, 52, 58).18 The HPV types covered by Gardasil 9 cause the vast majority of HPV-associated diseases in the United States and worldwide.19 Since January 2017, only Gardasil 9 has been available in the United States. Cervarix and Gardasil are still used in some other countries.

Two Vaccine Doses Are Sufficient to Protect Younger Adolescents

The Advisory Committee on Immunization Practices (ACIP) recommends routine HPV vaccination of girls and boys at 11 or 12 years of age.20 Initial recommendations for girls (in 2006) and boys (in 2011) called for a three-dose series.21-23 In 2016, ACIP updated its recommendation to indicate that adolescents who initiate the vaccine series before 15 years of age need only two doses (separated by 6-12 months).20 This update, which aligns with the World Health Organization recommendation,24 was based on evidence that two doses of the vaccine in younger adolescents produced an immune response similar to or higher than the response in young adults who received three doses.25 ACIP also recommends vaccination for females through age 26 and for males through age 21 who were not adequately vaccinated previously. Vaccination for some special populations is recommended through 26 years of age.20**

HPV Vaccines Are Safe and Effective

HPV vaccines are safe. All three vaccines have excellent safety profiles based on clinical trials and postapproval monitoring and evaluation in the United States and other countries.26-28 As of 2017, more than 270 million HPV vaccine doses had been distributed worldwide,26 including over 100 million in the United States.28 More than 100 studies that included 2.5 million people in 6 countries have found no serious adverse effects of HPV vaccination beyond what is typical for other adolescent vaccines.27 The Centers for Disease Control and Prevention and the FDA continue to monitor the safety of these vaccines, as for all vaccines.

HPV vaccines are highly effective. In clinical trials, among women who were not previously infected with HPV, the vaccines provided nearly complete protection against persistent HPV infection and cervical, vaginal, and vulvar precancers caused by vaccine-targeted HPV types.29-32 Women who were vaccinated as part of a clinical trial also had lower prevalence of oral HPV infections than did participants in the trial who were not vaccinated.33

Rates of vaccine-type cervical HPV infections and HPV cervical precancers have declined in the United States (Figure 2) and many countries following implementation of HPV vaccination programs.17,34-43 Early evidence suggests that HPV vaccination may be contributing to recent declines in cervical cancer incidence among young females,44,45 although further studies are needed to confirm these findings. In addition, lower rates of oral HPV infections have been documented among vaccinated compared with unvaccinated U.S. men and women (Figure 2).46 Reductions in genital warts also have been observed in the years following introduction of the vaccine;34 it is predicted that genital warts will be nearly eliminated in Australia as a result of HPV vaccination.47

Figure 2

Prevalence of Cervical HPV Infection, Cervical Precancers, and Oral HPV Infection in the HPV Vaccine Era

U.S. HPV Vaccine Uptake: Progress and Continuing Challenges

When the Panel’s 2012-2013 report on HPV vaccination was released, the most recent data indicated that only one-third of 13- to 17-year-old females and fewer than 7 percent of males had received the recommended three doses.48 Fortunately, there has been notable progress over the past five years.

• HPV vaccination has increased overall. In 2017, among those 13 to 17 years old, over half of females (53%) and more than one-third of males (44%) were up to date with respect to HPV vaccination (at least two doses for those who received their first HPV vaccine dose before age 15 and at least three doses for others; Figure 3). More than 65 percent of adolescents in this age group had received at least one dose of the vaccine, an increase over earlier years.7
• HPV vaccination of males has increased. When the Panel’s 2012-2013 report was released, vaccination coverage among adolescent boys lagged far behind that of girls, at least in part because the ACIP recommendation for boys was not issued until 2011. However, this gap is narrowing (Figure 3). Large increases in male vaccination rates have occurred across every stratum of age, race/ethnicity, and poverty level.49
• HPV vaccination has increased dramatically in some states and regions. In 2017, more than 80 percent of adolescents in two states (Rhode Island and Massachusetts) and the District of Columbia initiated the HPV vaccine series.7 Between 2013 and 2017, the percentage of adolescents who received their first dose of the HPV vaccine doubled or nearly doubled in four states (Utah, Arkansas, Virginia, and Montana). An additional 25 states increased one-dose coverage by more than 50 percent during this time period.7

Specific examples of successful efforts and programs are described later in the report (see Quality Improvement Initiative Improves HPV Vaccine Initiation and Completion, Rapid Adoption of the HPV Vaccine within a Health System, and School Program Increases HPV Vaccination in Rural North Dakota). Despite this progress, U.S. HPV vaccination rates do not meet the Healthy People 2020 goal—full vaccination of 80 percent of adolescents aged 13-15 years.50 Several statistics highlight the need to increase HPV vaccination rates throughout the United States.

• HPV vaccination coverage remains lower than that of other adolescent vaccines. HPV is one of three vaccines recommended for adolescents at age 11-12 years—the other two are the tetanus, diphtheria, and acellular pertussis vaccine (Tdap) and the meningococcal conjugate vaccine (MenACWY). In 2017, nearly 90 percent of 13- to 17-year-old adolescents received the Tdap vaccine, and 85 percent received the initial dose of MenACWY vaccine; however, only 49 percent had received all recommended doses of the HPV vaccine.7
• HPV vaccination coverage in the United States remains lower than in other countries. In Australia, in 2016, 79 percent of females and 73 percent of males had received three doses of the HPV vaccine by 15 years of age.51,52 In the United Kingdom, in 2016-2017, 83 percent of 13- to 14-year-old females had completed the two-dose HPV vaccination series.53 In the United States, however, among 13- to 17-year-olds, only 53 percent of females and 44 percent of males had received all recommended doses.7

• HPV vaccine uptake is uneven across the United States. HPV vaccination coverage varies substantially by state (Figure 4)—rates of up-to-date HPV vaccination range from a low of 29 percent in Mississippi to a high of 78 percent in the District of Columbia.7 No state or region has achieved the nation’s goal of full vaccination of 80 percent of adolescents. HPV vaccination rates are particularly low in rural areas, despite high uptake of other adolescent vaccines; over half of adolescents in urban areas are up to date on their HPV vaccination compared with only 42 percent in rural areas.7 There also are differences in vaccine uptake by race/ethnicity, socioeconomic status, and insurance status. The reasons for differences between populations are not fully understood.

Figure 3

Vaccine Uptake Among U.S. Adolescents Aged 13-17 Years, 2006-2017

Figure 4

Rates of Up-to-Date HPV Vaccination Among U.S. Adolescents Aged 13-17 Years, 2017

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