The World Health Organization's (WHO's) Strategic Advisory Group of Experts on Immunization (SAGE) has changed the recommendation for vaccines against human papillomavirus (HPV).
From the available evidence, SAGE has concluded that a single dose of vaccine offers solid protection against HPV, comparable to that achieved with two-dose schedules.
This could be a "game-changer for the prevention of the disease," as it would allow "more doses of the life-saving jab reach more girls," the WHO declared in a press release.
SAGE recommends updating HPV dose schedules as follows:
One- or two-dose schedule for the primary target of girls aged 9–14 years
One- or two-dose schedule for young women aged 15–20
Two doses with a 6-month interval for women older than 21
The HPV vaccine is highly effective for the prevention of HPV serotypes 16 and 18, which cause 70% of cases of cervical cancer, said Alejandro Cravioto, MD, PhD, SAGE chair, in a statement.
"SAGE urges all countries to introduce HPV vaccines and prioritize multi-age cohort catch up of missed and older cohorts of girls. These recommendations will enable more girls and women to be vaccinated and thus preventing them from having cervical cancer and all its consequences over the course of their lifetimes," he added.
For individuals who are immunocompromised, including those with HIV, three doses of the vaccine should be given if feasible, and if not, then at least two doses. There is limited evidence regarding the efficacy of a single dose in this group, the group noted.
Policymakers Need to Make Changes
Now that the WHO has deemed that one dose of HPV vaccine is sufficient, policymakers should make changes, say experts in a recent editorial comment published in The Lancet Oncology.
"Policy makers should consider modifying their HPV immunisation schedules for girls aged 9–14 years from a two-dose regimen to a one-dose regimen," write Jeff D'Souza, PhD, Institute for Better Health, Trillium Health Partners, Mississauga, Ontario, Canada, and David Nderitu, PhD, Egerton University, Nakuru County, Kenya.
Policymakers also need to consider reorienting their efforts on cervical cancer screening and treatment, and they should ensure that all girls globally have access to an effective HPV vaccination schedule, they add.
The editorialists also make a radical proposal.
Existing supply constraints of the HPV vaccine at the country level are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and related deaths occur in low- and middle-income countries (LMICs).
To overcome these problems, they suggest that "high-income countries that currently offer two-dose regimens to girls aged 9–14 years should consider opting for a one-dose vaccination schedule, and give any excess of vaccines to countries in greater need of them."
Two Doses in High-Income Countries
But it is unclear whether high-income countries are ready to move to a one-dose schedule.
Approached for comment, Maurie Markman, MD, president of medicine and science at Cancer Treatment Centers of America, Philadelphia, Pennsylvania, told Medscape Medical News that while he can't say for certain, he suspects that the US will be slower to accept this recommendation for a single dose of HPV vaccine "as a component of a 'standard-of-care' approach."
However, it "might formally acknowledge that if an individual/parent will only accept a single vaccine dose (or ultimately refuses to return for a recommended second dose), this will be considered a favorable outcome, both for the individual and society.
"I do not know if regulatory bodies in the US will accept the existing studies performed to address the one-dose vaccination strategy to rather dramatically change the approach in our country," he said. "The issue would be that if a single dose was stated to be a clinically acceptable option in the US, it would rapidly become the standard approach, and the regulators would want to be as certain as possible that this would not have a negative effect on what is now recognized to be a remarkably safe and effective cancer prevention effort."
Another expert who was approached for comment, Stephanie V. Blank, MD, professor of gynecologic oncology at the Icahn School of Medicine at Mount Sinai, said: "In higher-resourced countries, two doses are still preferred, as they are more effective than one.
"The modeling on which the SAGE recommendation is based is all from studies in LMICs and other modeling studies," she added.
At present, the Centers for Disease Control and Prevention recommends a two-dose schedule of HPV vaccines for individuals who receive the first dose before their 15th birthday. The three-dose schedule is recommended for those who receive the first dose on or after their 15th birthday and for people with certain immunocompromising conditions.
Studies have shown that two doses of HPV vaccine given to children aged 9 to 14 years provide as good or better protection than three doses given to older adolescents or young adults.
But even with a two-dose schedule, the WHO reports that uptake of the vaccine has been slow, and coverage is much lower than their 90% target. In 2020, global coverage with two doses was only 13%.
Factors that have influenced the slow uptake and low coverage of HPV vaccines include supply challenges, programmatic challenges, and costs related to delivering a two-dose regimen to older girls who are not typically included in childhood vaccination programs. The relatively high cost of HPV vaccines has also been problematic, particularly for middle-income countries.
Trials of One-Dose Schedules
The one-dose vaccine schedule has garnered a lot of interest, with several studies showing efficacy.
The KEN SHE trial, based in Kenya, showed that a single dose of the HPV vaccine was highly effective at preventing oncogenic infection, rivaling the protection offered by multidose regimens. Vaccine efficacy was 97.5% (P < .001) against HPV 16/18 for both the bivalent and monovalent vaccines, which is "comparable to that seen in multidose vaccine trials," the researchers noted.
A study in India found that efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95.4% for the single dose, 93.1% for the two-dose schedule, and 93.3% for the three-dose series.
Commenting on this trial in India in a recent interview with Medscape France, Geoffroy Canlorbe, MD, PhD, of the Department of Gynecologic and Breast Surgery and Oncology, Pitié-Salpêtrière Hospital, Paris, said the findings from India would need "to be confirmed by other studies." The results were nonetheless "excellent news for developing countries where there are challenges when it comes to access to vaccination."
Speaking at the 45th Congress of the French Society for Colposcopy and Cervical and Vaginal Diseases (SFCPCV), he emphasized that at this stage, the findings "cannot be extrapolated" to France. HPV vaccination coverage is low in France (it is estimated that the rate is 23.7%, placing the country 28th of 31 countries in Europe), and he recommended continuing with the two- or three-dose schedule for the time being.
"This poor coverage has nothing to do with healthcare-related logistical or organizational issues; instead, it has to do with people's mistrust when it comes to vaccination. Here, people who get the first dose get the subsequent ones," said Canlorbe. "The very fact of getting two to three doses allows the person's body to increase the production of antibodies and get a longer-lasting response to the vaccine."
Ethics of the Vaccine
In their editorial, D'Souza and Nderitu note that there are ethical considerations with the HPV vaccine that can "help guide deliberations, covering non-maleficence, beneficence, health equity, stewardship, and solidarity."
It would be inequitable and unjustifiable, they write, to offer a two-dose regimen to girls aged 9–14 years without also introducing multi-age cohort catch-up campaigns or programs for women who do not have access. "When it comes to an effective HPV vaccination schedule, no woman or girl should be left behind," they say.
To achieve the goal of eliminating cervical cancer, "countries must ensure that 90% of girls are vaccinated, 70% of women are screened, and 90% of women with precancerous lesions receive treatment and care," they write. "Given resource constraints, particularly in low-middle income countries, policy makers have a responsibility to ensure that resources are used in an optimal manner that promotes the right to health of all individuals."
Thus, countries that are lagging far behind in cervical cancer education, screening, and treatment should consider opting for a one-dose regimen for girls aged 9–14 years, as well as using additional resources to close the gap in these other areas.
Markman has relationships with Genentech, AstraZeneca, Celgene, Clovis, and Amgen; he is also a regular contributor to Medscape Oncology with the Markamn on Oncology video column. D'Souza and Nderitu have disclosed no relevant financial relationships.
Lancet Oncol. Published online June 20, 2022. Abstract
Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.
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Cite this: Single Dose of HPV Vaccine Is 'Game Changer,' Says WHO - Medscape - Jul 27, 2022.