A large-scale randomized control trial of Costa Rica reveals that one dose of a bivalent (two strain) or nonavalent (nine strain) human papillomavirus (HPV) vaccine provides the same protection against infection with HPV16 or HPV18 as the more common two-dose series, providing a potentially transformative tool for global cervical cancer prevention.
HPV types 16 and 18 are responsible for more than 77% of cervical cancers worldwide.
The study, published today in The New England Journal of Medicine (NEJM), enrolled 20,330 girls aged 12 to 16 and followed them for five years. The difference in rates between one and two doses of the bivalent vaccine was −0.13 infections per 100 participants, and the difference between one and two doses of the nonavalent vaccine was 0.21 infections per 100 participants. In all four trial groups, the vaccine was 97% effective and protection did not decline over the follow-up period.
“This is a very large study, and they evaluated a one-dose or two-dose strategy for two different versions of the HPV vaccine,” Kevin Ault, MD, an obstetrician-gynecologist at Western Michigan University Homer Stryker MD School of Medicine and author of several papers on the HPV vaccine, told CIDRAP News. “This study found very high efficacy in all groups, so one dose is equivalent to two doses.” Ault was not involved in the study.
The trial identified no safety concerns, a finding consistent with previous research. The safety profiles of HPV vaccines have been extensively evaluated in hundreds of millions of people, the study authors note.
“Given our current political environment, it is important to emphasize that [study] had a very, very, very high level of safety,” says Mark Einstein, MD, chair of the department of obstetrics, gynecology and women’s health at Montefiore Einstein in New York. Einstein was also not involved in the study.
“The strongest evidence yet” for the vaccine
Previous trials have shown that a single-dose regimen of the HPV vaccine can be as effective as two- or three-dose regimens. “So it’s not surprising that we see such high levels of what they call persistent infection prevention, which we know is a necessary step to get to cervical cancer,” Einstein says.
Eighty-five percent of cases and 90% of deaths from cervical cancer occur in low- and middle-income countries, where access to screening and treatment is limited and cost is a barrier.
In a NEJM editorial Accompanying the study, Ruanne Barnabas, MB, ChB, DPhil, of Massachusetts General Hospital and Harvard Medical School, describes the findings as “the strongest evidence to date” to support the World Health Organization’s (WHO) recommendation that girls and young women under the age of 20 receive one or two doses of the HPV vaccine.
Cervical cancer is the fourth most common cancer among women, with more than 660,000 new cases and 340,000 deaths in 2022, Barnabas notes. Eighty-five percent of cases and 90% of deaths from cervical cancer occur in low- and middle-income countries, where access to screening and treatment is limited and cost is a barrier.
“Most cervical cancers occur in places where vaccination is not available due to cost,” says Rebecca Perkins, MD, an obstetrician and gynecologist and researcher at the Institute for Research on Women, Mothers, and Babies at Tufts Medical Center, who was not involved in the study.
But the problem is not limited to low-income areas. Nearly two decades after the introduction of HPV vaccines, according to WHO estimates, only 30% of girls aged 9 to 14 worldwide have been vaccinated. Even in high-income countries like the United States, completion rates for multidose regimens remain suboptimal.
“I think that in countries like the United States, alternative dosing regimens should be discussed,” Einstein says. “Currently, we have a very low rate of compliance and completion of the full three-dose series. »
Opportunity to significantly improve cancer prevention worldwide
Single-dose vaccination would help low-, middle-, and high-income countries around the world overcome the challenge of getting people to return for multiple doses and strengthen the WHO’s cervical cancer elimination strategy, which calls for 90% of girls to be fully immunized by age 15, 70% of adult women to be screened during their lifetime, and 90% of women with cervical cancer to receive a appropriate treatment.
