One Dose of the HPV Vaccine Is over 97% Effective at Preventing HPV Infection

One dose of bivalent Cervarix (GlaxoSmithKline, Merck) and 9-valent Gardasil 9 (Merck) human papillomavirus (HPV) offers comparable protection compared with 2, with over 97% efficacy, according to data from the ESCUDDO trial (NCT03180034). The trial investigators hope the findings, presented at the 2025 American Association for Cancer Research Annual Meeting, help improve global HPV vaccine uptake and overcome vaccine hesitancy to reduce cervical cancer incidence and mortality over time.¹

Gardasil syringes | Image Credit: © Unshu - stock.adobe.com

HPV infection is responsible for 70% of all cervical cancers, as well as HPV precancers, genital warts, throat cancers, penile cancer, and anal cancer. The development of the HPV vaccine revolutionized cancer prevention by creating protection against HPV infection. The first vaccine became available in 2006 with the FDA approval of first-generation Gardasil, which protected against the 4 types of HPV: 6, 11, 16, and 18. In 2014, Gardasil 9 was approved to protect against 9 strains: 6, 11, 16, 18, 31, 33, 45, 52, and 58.²

Cervarix was approved by the FDA in 2009 for the prevention of cervical cancer, cervical intraepithelial neoplasia (CIN) grade 2 or worse and adenocarcinoma in situ, and CIN grade 1, caused by oncogenic HPV types 16 and 18, in females 9 through 25 years of age.³

"Nearly 20 years ago these vaccines were licensed, and global uptake in girls is 27% in the target-age population," Aimée Kreimer, PhD, of the National Cancer Institute, said in her presentation. "And this 27% is really a recent jump ... so it's been really slow."⁴

Despite their effectiveness, HPV vaccination rates remain low due to high costs and difficulty giving multiple doses. To help overcome cost barriers to widespread HPV vaccination, investigators assessed whether one dose of the HPV vaccine was as effective compared with the recommended 2 doses in a randomized, multi-arm trial. They enrolled over 20,000 girls between the ages of 12 and 16 residing in Costa Rica. The trial participants were randomized in 2 stages to 1 of 4 arms: one dose of the bivalent vaccine, 2 doses of the bivalent vaccine, one dose of the nonavalent vaccine, or 2 doses of the nonavalent vaccine.^1,5

At enrollment, individuals were first randomly assigned to receive one of the 2 study vaccines. At the second visit, participants were randomly randomized to receive either 1 or 2 doses of the relevant HPV vaccine. When the second dose of the vaccine was administered, those who were randomly assigned to the one-dose arm were given an active control, such as Tdap. The participants were monitored every 6 months for 5 years following immunization to detect antibody titers and ongoing cervical HPV infections, according to dose group and vaccine type.⁵

The primary outcomes measured in Cervarix and Gardasil 9 were the non-inferiority of 1 dose compared with 2 and 1 dose compared with no vaccination in each vaccine. The data showed that cumulative event rates of persistent HPV 16 and 18 infection of 6 months or more with either vaccine were not significantly different with one or 2 doses.¹

Health organizations such as the CDC emphasize its safety and effectiveness in preventing 90% of HPV infection-related cancers. Due to more widespread vaccination against HPV since 2006, infections decreased by 88% among teen girls and 81% in young adult women. In vaccinated women, the incidence of cervical precancers has dropped by 40%.⁶

"A global single-dose HPV vaccine recommendation should facilitate and accelerate country introductions and vaccine uptake," Kreimer said. "It really is high uptake of HPV vaccines that is going to control these diseases."⁵

REFERENCES

1. Comparing one or two doses of the human papillomavirus vaccine for the prevention of human papillomavirus infection, ESCUDDO Study (ESCUDDO). Updated May 4, 2025. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT03180034

2. The HPV vaccine: Access and use in the U.S. KFF. August 5, 2024. Accessed May 6, 2025. https://www.kff.org/womens-health-policy/fact-sheet/the-hpv-vaccine-access-and-use-in-the-u-s/#:~:text=The%20FDA%20approved%20first%2Dgeneration,was%20approved%20by%20the%20FDA.

3. Cervarix. FDA. October 25, 2019. Accessed May 6, 2025. https://www.fda.gov/vaccines-blood-biologics/vaccines/cervarix

4. One Dose of HPV vaccine noninferior to two, data show. MedPage Today. April 29, 2025. Accessed May 6, 2025. https://www.medpagetoday.com/meetingcoverage/aacr/115340?xid=nl_mpt_DHE_2025-04-29&mh=6d2b5f4f91352444bdf817a9c17750bc&zdee=gAAAAABm4uL9FCoIf1N83nrcwYYqnQUvN6Iw4dbaY-dGva4sOp57nSM2Ew3wD87ohRuoseQBDbCp1MG30J6ETpHXK1wNpp0NgnGTMFXrtFaNfWUoL5ekf-Y%3D&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Evening%20-%20Randomized%202025-04-29&utm_term=NL_Daily_DHE_dual-gmail-definition

5. ESCUDDO efficacy trial. National Cancer Institute. Accessed May 6, 2025. https://dceg.cancer.gov/research/cancer-types/cervix/escuddo

6. HPV vaccination. CDC. August 20, 2024. Accessed May 6, 2025. https://www.cdc.gov/hpv/vaccines/index.html