Bivalent HPV Vaccine Induces Robust Serologic Response Nine Years Postvaccination

HPV vaccination
In addition to high antibody levels, factors including exposure to the human papillomavirus (HPV) and antibody avidity may be important and necessary to protect against infection.

In addition to high antibody levels, factors including exposure to the human papillomavirus (HPV) and antibody avidity may be important and necessary to protect against infection, according to research published in the Journal of Infectious Diseases.

Using data from a prospective cohort study (the HPV Among Vaccinated And Non-Vaccinated Adolescents), researchers examined participant characteristics and antibody levels in vaccinated women with and without HPV-DNA infections to determine whether higher antibody levels protect against infection with HPV strains 16, 18, 31, 33, 45, 52, or 58.

The total initial study population included 1038 women, of whom 71.7% were vaccinated. By year 9 postvaccination, the number of participants fell to 514 (76.7% vaccinated). Within this cohort, investigators observed a total of 204 incident and 64 persistent infections with HPV strains 16, 18, 31, 33, 45, 52, or 58.

Across all postvaccination years, investigators noted significant differences in seroprevalence between the vaccinated and unvaccinated groups for all HPV types. Among the vaccinated women, seropositivity was attained in 100% for vaccine types HPV 16/18 directly after vaccination and remained at 100% up to 9 years postvaccination. Among women who were unvaccinated, 9.7% and 4.8% demonstrated seropositivity in the first year of follow-up and increased to 20.8% and 9.3% in the last year for HPV16 and HPV18, respectively. A remarkably higher seroprevalence among those who were vaccinated was noted for other HPV types compared with those who were unvaccinated.

Between both groups, pre-vaccination geometric mean concentrations were comparable. Significant differences were noted between vaccinated and unvaccinated participants at all timepoints thereafter. Antibodies for vaccine types HPV 16/18 peaked after vaccination, followed by a significant decline 3 years postvaccination, with geometric mean concentrations remaining high and fairly stable up to 9 years postvaccination.

Risk factors for contracting a vaccine type/cross protective type or nonvaccine type of HPV infection 1-year pre-infection included smoking and characteristics of sexual behavior. No substantial differences in risk factors were noted for any of the investigated strains of HPV.

Investigators did not find any consistent significant differences in immunoglobulin G antibody levels 1-year pre-infection between those who were vaccinated either with or without an infection in the next year. Significant differences were noted for nonvaccine type HPV 52, and a geometric mean concentration ratio of 1.57 (95% CI, 1.33-1.87) and 2.09 (95% CI, 1.63-2.70) was noted for both incident and persistent infections, respectively, showing higher antibody levels in uninfected vs infected individuals in the year before infection.

Study limitations included the limited number of type-specific HPV infections available for analysis, as well as challenges in the detection of infections and a lack of information on the exact timing of infection acquisition.

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“While antibody concentrations remain an important monitoring tool at population level, the question remains how insightful they are at [the] individual level as long as a cut-off for protection is lacking and infections still occur despite high antibody levels,” the researchers concluded. “For future studies, it remains important to monitor vaccine responses, but also failures to see how infections occur and whether they can still induce lesions.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Hoes J, Pasmans H, Knol MJ, et al. Persisting antibody response nine years after bivalent HPV vaccination in a cohort of Dutch women: Immune response and the relation with genital HPV infections [published online January 9, 2020]. J Infect Dis. doi: 10.1093/infdis/jiaa007