Analysis suggests HPV vaccine protects unvaccinated people through herd immunity

Our best hope to eliminate cervical cancer

Laine Bergeson

A new nationwide cohort study from Sweden suggests that widespread human papillomavirus (HPV) vaccination could substantially reduce the risk of precancerous lesions even among people who never received the vaccine.

The study, published in The Lancet Public Health, examined rates of high-grade cervical lesions (HSIL+) among more than 850,000 unvaccinated girls and women born from 1985 to 2000 by using national vaccination registries. 

A team led by researchers from the Karolinska Institutet in Stockholm compared outcomes across cohorts exposed to different HPV vaccination strategies, including largely opportunistic vaccination (when people are offered a vaccine as part of a routine doctor visit or other interaction with the health care system), subsidized vaccination, catch-up vaccination, and school-based vaccination. 

Among unvaccinated women born in 1999 or 2000 and eligible for school-based vaccination programs that attained coverage greater than 80%, HSIL+ incidence was about 50% lower than in unvaccinated women from birth cohorts before vaccination was widespread. 

At age 23 years, the incidence rate ratio for the 1999–2000 cohort was 0.53 (95% confidence interval [CI], 0.39 to 0.77). In the subsidized vaccination cohort (1989–92), the age-adjusted incidence rate ratio was 1.18 (95% CI, 1.15 to 1.20). In the catch-up vaccination cohort (1993–98), the age-adjusted incidence rate ratio was 1.03 (0.99 to 1.06). 

Vaccination sharply reduces precancerous lesions

Nearly all cervical cancers are caused by HPV infection, and vaccination has been shown to sharply reduce infections and precancerous lesions. Herd protection refers to the indirect benefit of HPV vaccines for unvaccinated people. When enough people are vaccinated, the virus’s overall spread in the community drops. As a result, unvaccinated women and girls are less likely to be exposed to HPV infection and related disease.

In an accompanying commentary, Nicolas Wentzensen, MD, PhD, of the National Cancer Institute, and Nicole Campos, PhD, of the Harvard T.H. Chan School of Public Health, caution that estimating herd effects is challenging, particularly because models of what disease rates would have looked like without vaccination do not exist. Differences in sexual behavior, screening practices, and immunologic differences across birth cohorts can complicate interpretation.

Still, Wentzensen and Campos write, “The models and observational data both suggest that there is a herd effect on the incidence of cervical lesions,” even as “the magnitude of this effect is difficult to establish.”

The study’s strengths include its large size and use of registry data, which help minimize selection bias. Plus, the extensive data source allows generalization to other countries with similar screening programs and HPV vaccination recommendations. 

“Importantly,” write the study authors, “by studying cohorts exposed to different vaccination strategies, we were able to assess the varying effects of these programmes on unvaccinated women, providing valuable insights into the potential herd effects of HPV vaccination.”