Approximately 90% of deaths from cervical cancer occur in low- and middle-income countries (LMIC). Human papillomavirus (HPV) vaccines are highly effective and, since their introduction, have significantly reduced vaccine-type HPV infections and precancerous cervical lesions. However, access to HPV vaccines in these countries has been limited—only 19 LMIC currently deliver HPV vaccinations as part of national programs.
The HPV vaccination schedule has been reduced before. In 2014, the WHO reduced the schedule from three doses to two, following an evidence review by the Strategic Advisory Group of Experts (SAGE) on Immunization. Now, new evidence has emerged to suggest a single dose of HPV vaccine may be sufficient to elicit a protective immune response against HPV infection.
The Single-Dose HPV Vaccine Evaluation Consortium, managed by PATH, released its second comprehensive review of evidence on a single-dose HPV vaccination schedule. The review includes current public evidence from clinical trials, immunogenicity studies, other observational studies, and impact modeling. The consortium is also generating new evidence within these areas. Their goal is to evaluate this evidence in order to inform global policy discussions and program guidance, as well as to raise awareness of its implications for national immunization programs.
So far, the evidence is encouraging. In randomized controlled trials (RCT) where girls did not complete their multi-dose schedule, evidence suggests that a single dose of HPV vaccine may provide protection against persistent HPV infection. This evidence is being strengthened by additional RCTs currently underway. Several more studies have found significant vaccine effectiveness for single-dose HPV vaccination. Initial findings of modeling analyses suggest that giving one dose of HPV vaccine will yield much greater health benefits than none at all, even if the vaccine does not protect as well as two doses.
What could a single-dose schedule mean for girls all over the world?
HPV vaccine delivery is challenging because the WHO-recommended target age group is 9 to 14-year-old girls—rather than infants under 12 months of age, as it is with most routine immunizations. Girls between 9 and 14 generally do not attend health facilities for regular services, so delivery strategies must vary widely from school- and facility-based approaches to outreach campaigns. Following up with girls for the second dose also poses challenges. A single-dose HPV vaccination schedule could alleviate the financial and logistical barriers countries face, accelerate HPV vaccine introduction into national immunization schedules, and achieve higher coverage in current country programs.
HPV vaccine supply also poses a challenge. The supply currently available to LMICs is insufficient to meet demand in 2020 and 2021, leaving them unable to scale-up HPV vaccination programs per WHO recommendations. As of 2017, the WHO recommended countries vaccinate a multi-age cohort of all 9-14-year-olds in the first year of introduction and then continue with routine immunization of 9-year-olds in the second year to accelerate impact. In the context of the supply constraint, SAGE recommended that countries that already have HPV vaccine on the national schedule employ alternative strategies until the supply allows equitable access in all countries. These strategies include pausing vaccinations in boys, older girls (>15 years), and multi-age cohorts; or adopting an extended interval between doses.
New and forthcoming evidence on the potential for a single-dose vaccination schedule could help alleviate future supply issues and accelerate new introductions. Additionally, new HPV vaccines will be available from developing country manufacturers in the coming years providing more access to HPV vaccine supply.
The Single-Dose HPV Vaccine Evaluation Consortium will continue to monitor the evidence base and will provide another update to the review at the end of this year.
Learn more in the review and summaries: