World Health Organization: A Single HPV Vaccine Dose Could Be a Game Changer

The HPV virus and its subtypes cause many diseases in humans, from simple warts to cervical and head and neck cancers. We know that 5-6% of all cancers and approximately cervical cancers in 99% of cases are associated with HPV. The serious consequences of HPV infections can largely be prevented with available vaccines, but citizens of many countries struggle to access them, and awareness remains inadequate. 

Based on current evidence, SAGE concluded that a single-dose schedule provides solid protection against HPV comparable to the results of a two-dose schedule.

In a press release, WHO said: “This new strategy could be a game changer for disease prevention because it will allow the lifesaving vaccine to reach more women.”

SAGE recommends updating HPV dose schedules as follows:

• A one- or two-dose schedule for the primary target group of girls aged 9-14
• A one- or two-dose schedule for young women aged 15-20
• Two doses 6 months apart for women older than 21

HPV serotypes 16 and 18 account for 70% of cervical cancer cases. SAGE chair Alejandro Cravioto said the vaccine is highly effective in preventing cervical cancers caused by serotypes 16 and 18.

“SAGE urges all countries to introduce HPV vaccination and prioritize vaccination of women across multiple age groups. These recommendations will allow more girls and women to be vaccinated, protecting them throughout their lives from cervical cancer and all its consequences.”

However, HPV does not cause only cervical cancer. It also plays a major role in head and neck, anal, vaginal-vulvar and penile cancers. Many Western countries therefore recommend vaccination against HPV for boys and young adult men in their health guidelines.

People living with HIV and other immunocompromised individuals should receive three doses if possible, or at least two if not. SAGE notes that evidence for the effectiveness of a single dose in these groups is limited.

Policymakers Also Need to Make Changes

Experts said in a recent editorial in The Lancet Oncology that, now WHO has determined that one HPV vaccine dose is sufficient, policymakers should also make changes.

Jeff D'Souza of the Institute for Better Health in Canada and David Nderitu of Egerton University in Kenya wrote: “Policymakers should consider changing HPV vaccination programs for girls aged 9-14 from a two-dose to a single-dose regimen.”

The editorial authors add that policymakers should redirect attention to cervical cancer screening and treatment and ensure that all girls globally can access an effective HPV vaccination program. They also make a radical proposal.

Current global supply constraints on HPV vaccines are expected to continue for the next 3 years, and the vast majority of new cervical cancer cases and deaths occur in low- and middle-income countries. To address these problems, they propose: “High-income countries currently offering two doses to girls aged 9-14 should consider choosing a single-dose schedule and giving surplus vaccines to countries with greater need.”

Two Vaccine Doses in High-Income Countries

However, it is unclear whether high-income countries are ready to switch to a single-dose program.

Maurie Markman, president of Medicine and Science at Cancer Treatment Centers of America, suspects, without stating it definitively, that as part of its “standard care” approach, the United States will be slower to accept this recommendation for a single HPV vaccine dose.

However, “it could formally recognize that if an individual or parent accepts only a single vaccine dose, or refuses to return for a recommended second dose, this would be considered a positive outcome for both the individual and society.”

“I do not know whether regulators in the United States will accept current studies examining a single-dose vaccination strategy to change the approach in this country quite dramatically. The issue is that, if a single dose is described as a clinically acceptable option in the United States, it will quickly become standard practice. Regulators will want to be as certain as possible that this will not adversely affect what is currently considered a very safe and effective cancer-prevention effort.”

Professor of Gynecologic Oncology Stephanie V. Blank of the Icahn School of Medicine at Mount Sinai says: “Two doses are still preferred in higher-resource countries because they are more effective than one. The modeling on which SAGE's recommendation is based comes from studies in low-income countries and other modeling studies.”

The United States Centers for Disease Control and Prevention (US-CDC) currently recommends two HPV vaccine doses for those who receive their first dose before age 15. It recommends three doses for those receiving their first dose at age 15 or later and those with certain immunocompromising conditions.

Even with a two-dose program, however, WHO reports slow uptake and coverage far below its 90% targets. Global coverage for the two-dose schedule was only 13% in 2020.

Factors contributing to slow HPV vaccine uptake and low coverage include supply and programmatic challenges and the costs of delivering a two-dose regimen to older females not typically included in childhood vaccination programs. Relatively high vaccine prices have also been a problem, particularly for middle-income countries.

Studies of Single-Dose Schedules

A single-dose schedule has attracted considerable interest following several studies showing its effectiveness. The Kenya-based KEN SHE trial showed that a single HPV vaccine dose was highly effective in preventing oncogenic infection, rivaling the protection of multidose regimens. Researchers reported 97.5% efficacy against HPV 16/18 for both bivalent and monovalent vaccines, “comparable to that seen in multidose vaccine trials” .

A study in India found evaluable efficacy against persistent HPV 16 and 18 infection of 95.4% for a single dose, 93.1% for two doses and 93.3% for a three-dose series.

Geoffroy Canlorbe of the Department of Gynecological and Breast Surgery and Oncology at Pitié-Salpêtrière Hospital in Paris commented on the Indian study: “The findings from the study in India need to be confirmed by other studies. Nevertheless, the results are excellent news for developing countries where access to vaccination is difficult.”

HPV vaccination coverage is low in France (the rate is thought to be 23.7%, placing the country 28th among 31 European countries), and Canlorbe recommends continuing with the two- or three-dose schedule for now.

“This insufficient coverage has nothing to do with logistical or organizational health issues; it relates to people's distrust of vaccination. Here, those who receive the first dose already receive the subsequent doses. Receiving two to three vaccine doses allows the body to increase antibody production and achieve a longer-lasting response to vaccination.”

Vaccine Ethics

D’Souza and Nderitu make the following point about ethics: “There are ethical considerations that can help guide deliberations about HPV vaccination, encompassing nonmaleficence, beneficence, health equity, stewardship and solidarity.”

Offering a two-dose regimen to girls aged 9-14 while not launching catch-up vaccination campaigns or programs for women without access or for much older groups would be unjust and unfair.  

“No woman or girl should be left behind when it comes to an effective HPV vaccination schedule.”

“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. Given resource constraints, particularly in low- and middle-income countries, policymakers have a responsibility to ensure that resources are used optimally to support every individual's right to health.”

Therefore, countries that lag far behind in cervical cancer education, screening and treatment should consider choosing a single-dose regimen for girls aged 9-14 and using additional resources to close gaps in other areas.

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The FDA (United States Food and Drug Administration) has approved 3 vaccines for the prevention of HPV infections:

• Bivalent vaccine (Cervarix): Available in Turkey
• Quadrivalent vaccine (Gardasil): Available in Turkey
• 9-valent vaccine (Gardasil 9): Not available in Turkey

The HPV types against which these vaccines provide protection are shown below: