On December 20, 2022, the World Health Organization (WHO) updated its recommendations for cervical cancer vaccines in a bid to boost vaccination coverage.

The WHO now says that a one-dose schedule for girls ages 9–14 years adequately protects against human papillomavirus (HPV), and more specifically, the HPV 16 and HPV 18 strains. The insights and amendments came following findings from a meeting held by WHO’s independent expert advisory group in April 2022.

Several cervical cancer vaccines are currently approved, including Merck’s nonavalent vaccine Gardasil 9 and GSK’s bivalent vaccine Cervarix. In September 2022, the Drugs Controller General of India (DCGI) approved its first indigenously produced quadrivalent cervical cancer vaccine, developed by the Serum Institute of India.

“The HPV vaccine works almost perfectly to prevent HPV infection, the necessary cause of cervical cancer and other HPV-related cancers,” says Dr. Ruanne Barnabas, professor of Medicine at Harvard Medical School and researcher on the study that informed the WHO’s updated recommendations. “The vaccine is also safe, with millions of doses administered globally,” she continues.

Potential changes with a single-dose schedule

“Before the new WHO guidelines, either two or three doses of the current vaccines were administered,”says Barnabas. People up to age 14 years were given two doses of the vaccine, and those ages 15 years and older received three doses. All prophylactic HPV vaccine products are delivered intramuscularly in the arm, specifically the deltoid region, at a standard dose of 0.5ml.

After studying the single-dose bivalent and nonavalent HPV vaccines, researchers found that they were both highly effective in avoiding incident persistent oncogenic HPV infection, similar to multidose programs. Current HPV vaccination coverage levels sit at 15%, Barnabas shares, compared to the WHO’s goal of giving 90% of eligible adolescents, or those ages 9–14 years, the HPV vaccine.

The cost of HPV vaccines is also high compared to other vaccines,” Barnabas adds. The ability to use one dose would decrease the program’s overall cost, making the vaccine more accessible to more people. This would be the key improvement” of a single-dose schedule, says Barnabas.

For low-resource countries that have not yet introduced the vaccine, particularly middle-income countries (MICs) that are eligible for supplies from the nonprofit GAVI, the singular dose will lower the budget requirement for HPV, says Paul Bloem, Technical Officer, Lead HPV vaccine strategy of the Immunization, Vaccines and Biologicals (IVB) Department at the WHO. A new vaccine like HPV, which is relatively more expensive than a traditional one like the diphtheria, pertussis, and tetanus (DTP) vaccine, can significantly increase the overall budget of a national vaccination program. “The single dose will lower that barrier,” Bloem confirms.

A single-dose schedule offers opportunities for ease of delivery and the possibility to add HPV to other one-off campaigns to boost coverage. It may also result in fewer administrative requirements compared to full-dose schedule tracking. Programs to catch up with older age groups, such as those up to age 18 years, could also benefit from requiring one dose rather than three.

New schedule rollout

As the WHO issues new guidance, each country is expected to take steps to increase the impact of its vaccination program.

Democratizing access to the vaccine appears to be a key goal of the single-dose vaccine, particularly as its cost is a barrier. The study that led to the WHO’s recommendations found that 80% of new cervical cancer cases are in women living in low-income and MIC, with the highest mortality found in sub-Saharan Africa. One 2022 study found that cervical cancer accounts for the second-highest cancer burden among women of all ages in Nigeria. Overcoming health system limitations related to health worker availability, infrastructure, and logistics is crucial, the study revealed, as is social awareness and mobilization.

However, a 2021 research study found that despite the implementation of vaccination programs, there is low awareness of HPV infection and its vaccine, particularly in developing countries. The WHO’s 2020 global strategy sets out its vision of cervical cancer being eliminated as a public health problem by 2030 and outlines a pathway with strategic actions to achieve its goal.

While Bloem said high-income countries (HIC) like the UK are moving to a one-dose schedule, he expected others to shift in the next few years while some, particularly Upper-MIC and HIC, may wait.

Current vaccination rates are variable

According to the data published in July 2022, the global vaccine coverage by full dose is 12%, and by single dose is 15%. The North American region has the highest vaccine coverage (38%), although coverage was at more than 50% before the Covid-19 pandemic, followed by Europe (27%) and the African region (21%). Asia has less than 10% vaccine coverage because two big countries, India and China, are yet to introduce it [on a national level], Bloem says. Australia is on track to eliminate cervical cancer as a public health problem.

Various barriers have led to vaccination rates in most parts of the world remaining relatively low. “The main obstacles have been the high vaccine cost, low supply, and insufficient advocacy,” says Barnabas. Many countries struggle with HPV vaccination communication despite their income status. “Even though the WHO has repeatedly evaluated and announced that the HPV vaccine is an extremely safe vaccine, vaccine hesitancy still remains an issue,” says Bloem.

Additionally, the sexual transmission of HPV has been an “unnecessary focus of attention”, Barnabas shares, stating that the lifetime risk of HPV is almost 100% for sexually active persons, and thus, HPV is part of everyday life.

“Given that almost 100% of cervical cancers are caused by HPV and that the vaccine is nearly perfect in preventing almost 100% of infections, effective programs would prevent disease and death among women in their mid-adult years and contribute to healthier families and communities,” Barnabas shares.

Another challenge is a programmatic one, Bloem highlights, since the HPV vaccine is somewhat unique compared with childhood vaccines in terms of target age and sex. The primary target cohort is girls ages 9–14 years, which stands alone from other childhood vaccine services.

Since these adolescents are less likely to come to the hospital than babies and children, the focus needs to be on actively reaching out to those populations by using available platforms, such as school-based vaccinations. However, in some resource-limited countries, it is hard to reach those cohorts due to low school attendance rates, geographical challenges, and religious barriers.