New research indicates that a single dose of the human papillomavirus (HPV) vaccine is as effective as multiple doses for preventing preinvasive cervical disease, which can later develop into cervical cancer.
The findings are published early online in Cancer, a peer-reviewed journal of the American Cancer Society (ACS).
HPV is the most common sexually transmitted infection in the United States, and persistent infection with certain types of the virus can cause cervical cancer.
To prevent infection, the Centers for Disease Control and Prevention recommends that adolescents – both boys and girls -under the age of 15 years receive a two-dose schedule of the HPV vaccine.
To determine the effectiveness of other dose schedules, Ana M. Rodriguez, MD, MPH, of The University of Texas Medical Branch at Galveston, and her colleagues examined information on females aged 9 to 26 years who were unvaccinated or who received one or more HPV vaccine doses between January 2006 and June 2015.
The analysis included 133,082 females (66,541 vaccinated and 66,541 unvaccinated). For females ages 15 to 19 years, those who received one, two, or three doses of the HPV vaccine had lower rates of preinvasive cervical disease than adolescents who were unvaccinated.
Within five years, 2.65 percent of unvaccinated teens aged 15 to 19 years developed preinvasive cervical disease, compared with 1.62 percent, 1.99 percent, and 1.86 percent in the one-, two- and three-dose groups, respectively.
The risk of preinvasive cervical disease was 36 percent, 28 percent, and 34 percent lower for adolescents who received one, two, and three doses, respectively, compared with adolescents who were unvaccinated.
For the youngest (less than 15 years old) and oldest age groups (20 years and older), the investigators did not find significant differences among the vaccinated groups in terms of risk for preinvasive cervical disease.
“This study shows the impact of vaccinating at younger ages and its lasting long-term protection against cervical cancer,” said Dr. Rodriguez.
“It is important to educate parents about the need to vaccinate their children.”
An accompanying editorial discusses the public health implications of the study’s findings.
“If one dose of HPV vaccine was sufficient for effective protection, HPV vaccine implementation and scale-up would require less logistics…, available doses could extend further, and the overall cost would be lower,” the authors wrote.
February is National Cancer Prevention Month.
What are HPV vaccines?
HPV vaccines are vaccines that protect against infection with human papillomaviruses (HPV). HPV is a group of more than 200 related viruses, of which more than 40 are spread through direct sexual contact. Among these, two HPV types cause genital warts, and about a dozen HPV types can cause certain types of cancer—cervical, anal, oropharyngeal, penile, vulvar, and vaginal.
Three vaccines that prevent infection with disease-causing HPV types are licensed for use in the United States: Gardasil®, Gardasil® 9, and Cervarix®. All three vaccines prevent infection with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-caused cancers (1, 2). Gardasil also prevents infection with HPV types 6 and 11, which cause 90% of genital warts (3). Gardasil 9 prevents infection with the same four HPV types plus five additional cancer-causing types (31, 33, 45, 52, and 58) that together account for 10 to 20% of cervical cancers.
Gardasil 9 is now the only HPV vaccine available for use in the United States. Cervarix and Gardasil are still used in other countries.
Who should get HPV vaccination?
The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) develops recommendations regarding all vaccination in the United States, including HPV vaccination. The current ACIP (CDC) recommendations for HPV vaccination are as follows (4):
- Children and adults ages 9 through 26 years. HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be started as early as age 9 years. HPV vaccination is recommended for all persons through age 26 years who were not adequately vaccinated earlier.
- Adults ages 27 through 45 years. Although the HPV vaccine is Food and Drug Administration (FDA) approved to be given through age 45 years, HPV vaccination is not recommended for all adults ages 27 through 45 years. Instead, ACIP recommends that clinicians consider discussing with their patients in this age group who were not adequately vaccinated earlier whether HPV vaccination is right for them. HPV vaccination in this age range provides less benefit because more people have already been exposed to the virus.
- Persons who are pregnant. HPV vaccination should be delayed until after pregnancy, but pregnancy testing is not required before vaccination. There is no evidence that vaccination will affect a pregnancy or harm a fetus.
How many doses of the HPV vaccine are needed?
Children who start the vaccine series before their 15th birthday need only two doses to be fully protected. People who start the series at age 15 or older and people who have certain conditions that weaken the immune system need three doses to be fully protected.
Researchers are currently investigating whether a single dose of HPV vaccine might be effective
How effective are HPV vaccines?
HPV vaccines are highly effective in preventing infection with the types of HPV they target when given before initial exposure to the virus—which means before individuals begin to engage in sexual activity.
In the trials that led to the approval of Gardasil and Cervarix, these vaccines were found to provide nearly 100% protection against persistent cervical infections with HPV types 16 and 18 and the cervical cell changes that these persistent infections can cause.
The trials that led to approval of Gardasil 9 found it to be nearly 100% effective in preventing cervical, vulvar, and vaginal disease caused by the five additional HPV types (31, 33, 45, 52, and 58) that it targets (6).
In a 2017 position paper, the World Health Organization stated that the HPV vaccines have equivalent efficacy (7). The Cervarix vaccine has been found to provide partial protection against a few additional HPV types not included in the vaccine that can cause cancer, a phenomenon called cross-protection (8).
A 2019 meta-analysis of girls-only HPV vaccination programs in 14 countries that included more than 60 million vaccinated people showed strong evidence of the vaccine’s effectiveness (9). For example, compared with the period before vaccination began,
- infections with HPV 16 and 18 decreased by 83% among girls aged 15–19 years and by 66% among women aged 20–24 years at up to 8 years after vaccination began
- diagnoses of anogenital warts decreased by 67% among girls aged 15–19 years and by 54% among women aged 20–24 years at up to 9 years after vaccination began
- the prevalence of precancerous lesions that can lead to cervical cancer decreased by 51% among girls aged 15–19 years and by 31% among women aged 20–24 years at up to 9 years after vaccination began.
To date, protection against the targeted HPV types has been found to last for at least 10 years with Gardasil (10), at least 9 years with Cervarix (11), and at least 6 years with Gardasil 9 (12). Long-term studies of vaccine efficacy that are still in progress will help scientists better understand the total duration of protection.
A clinical trial of Gardasil in men indicated that it can prevent anal cell changes caused by persistent infection and genital warts (13). Analyses of data from women participating in a clinical trial of Cervarix found that this vaccine can protect women against persistent HPV 16 and 18 infections in the anus (14) and the oral cavity (15).
Why is it important for people to follow HPV vaccination recommendations?
The combination of HPV vaccination and cervical screening can provide the greatest protection against cervical cancer.
Also, vaccination is the approved public health intervention for reducing the risk of developing HPV-associated cancers at sites other than the cervix.
It is important that as many people as possible in the recommended age group get vaccinated.
Not only does vaccination protect vaccinated individuals against infection by the HPV types targeted by the respective vaccine, but also vaccination of a significant proportion of the population can reduce the prevalence of the vaccine-targeted HPV types in the population, thereby providing some protection for individuals who are not vaccinated (a phenomenon called herd immunity).
For example, in Australia, where a high proportion of girls are vaccinated with Gardasil, the incidence of genital warts went down during the first 4 years of the vaccination program among young males—who were not being vaccinated at the time—as well as among young females (16).
Further evidence that large-scale HPV vaccination confers protection for unvaccinated individuals comes from a 2019 meta-analysis of girls-only HPV vaccination programs in 14 high-income countries that included 60 million vaccinated people (9).
That analysis showed that, up to 8 years after the start of vaccination, diagnoses of anogenital warts decreased by 31% among women aged 25–29 years, by 48% among boys aged 15–19 years, and by 32% among men aged 20–24 years, compared with the period before vaccination began.
In addition, the vaccines may reduce the need for screening and subsequent medical care, biopsies, and invasive procedures associated with follow-up from abnormal cervical screening, thus helping to reduce health care costs and anxieties related to follow-up procedures (17).
Until recently, the other cancers caused by HPV were less common than cervical cancer. However, the incidence of HPV-positive oropharyngeal cancer and anal cancer has been increasing in the United States (18) while the incidence of cervical cancer has declined, due mainly to highly effective cervical cancer screening programs.
Therefore, in the United States, non-cervical cancers caused by HPV are now as common as cervical cancers. In addition, most of the HPV-positive non-cervical cancers arise in men.
There are no formal screening programs for the non-cervical cancers, so universal vaccination could have an important public health benefit.
How safe are HPV vaccines?
Before they could be licensed, all three HPV vaccines were tested for safety and efficacy in tens of thousands of people in the United States and many other countries.
Since licensure, millions of individuals have been vaccinated and, thus far, no serious side effects have been shown to be caused by the vaccines.
The most common problems have been brief soreness and other local symptoms at the injection site. These problems are similar to those commonly experienced with other vaccines.
A safety review by the FDA and the CDC considered adverse side effects related to Gardasil immunization that have been reported to the Vaccine Adverse Events Reporting System since the vaccine was licensed (19–21).
The rates of adverse side effects in the safety review were consistent with what was seen in safety studies carried out before the vaccine was approved and were similar to those seen with other vaccines.
However, a higher proportion of syncope (fainting) and venous thromboembolic events (blood clots) were seen with Gardasil than are usually seen with other vaccines. The patients who developed blood clots had known risk factors for developing them, such as taking oral contraceptives.
A safety review of Gardasil in Denmark and Sweden did not identify an increased risk of blood clots (20).
The most recent safety data review for HPV vaccines continues to indicate that these vaccines are safe (22).
Falls after fainting may sometimes cause serious injuries, such as head injuries. These can largely be prevented by keeping the person seated for up to 15 minutes after vaccination.
The FDA and CDC have reminded health care providers that, to prevent falls and injuries, all vaccine recipients should remain seated or lying down and be closely observed for 15 minutes after vaccination. More information is available from the CDC at http://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html.
More information: “Comparison of the long-term impact and clinical outcomes of fewer doses versus standard doses of human papillomavirus vaccine in the United States: a database study.” Ana M. Rodriguez, Burak Zeybek, Micah Vaughn, Jordan Westra, Sapna Kaul, Jane R. Montealegre, Yu-Li Lin, and Yong-Fang Kuo, PhD. Cancer (2020). DOI: 10.1002/cncr.32700