Quadrivalent human papillomavirus (HPV) vaccination led to a significantly reduced risk of invasive cervical cancer that was sustained through long-term follow-up, according to the results of a Swedish nationwide, register-based cohort study published in The BMJ.
“This study provides evidence of sustained protection against invasive cervical cancer throughout 18 years of follow-up, with no indication of waning protection. These findings further support global strategies for eliminating cervical cancer as a public health problem by achieving high coverage of routine HPV vaccination,” said the study authors, led by Shiqiang Wu, a doctoral student in the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm.
Study Methods
Researchers wanted to evaluate the long-term risks for invasive cervical cancer following quadrivalent HPV vaccination, with a focus on how risk varies with time and the population level impact of HPV vaccination programs.
They assessed 926,362 girls and women in Sweden between the years of 2006 and 2023. These girls and women were born between 1985 and 2001, with cohorts divided by their birth years, and none had received an HPV vaccination or prior diagnosis of invasive cervical cancer prior to 2006. They were followed for a maximum of 38 years.
The researchers calculated incidence rate ratios for vaccinated vs unvaccinated women and stratified the findings into 3-year intervals and according to the age at vaccination and by the birth year cohorts.
Key Findings
Across all participants, 39.5% received at least one dose of the quadrivalent HPV vaccine. Invasive cervical cancer was identified in 930 women, including 97 who were vaccinated and 833 who were not.
In women who were vaccinated before they were 17 years old, the overall fully adjusted incidence rate ratio was 0.21 (95% confidence interval [CI] = 0.13–0.32) compared with unvaccinated women. Protection again cervical cancer was sustained for 13 to 15 years after the initial vaccination (incidence rate ratio = 0.23; 95% CI = 0.11–0.46).
Among those vaccinated at 17 years or older, the overall fully adjusted incidence rate ratio was 0.63 (95% CI = 0.49–0.81) vs unvaccinated women. For this group, significant reductions in incidence were observed during years 10 through 12 (incidence rate ratio = 0.54; 95% CI = 0.33–0.86) and years 13 through 15 (incidence rate ratio = 0.23; 95% CI = 0.08–0.60) following vaccination.
“We found sustained risk reduction of invasive cervical cancer after quadrivalent HPV vaccine. No indication of waning protection was observed among the vaccinated population,” Wu et al added.
The cohort of women born between 1999 and 2001 had a 72% (95% CI = 11%–91%) lower risk of cervical cancer compared with women born between 1985 and 1988, after adjusting for covariates (incidence rate ratio = 0.28; 95% CI = 0.09–0.89). This amounted to a rate of invasive cervical cancer of 250 cases per 100,000 by age 38 in the oldest population studied vs 4 cases per 100,000 by age 24 in the youngest population studied.
“These findings further support global strategies aimed at cervical cancer elimination through high vaccine coverage, particularly in younger populations, and emphasize the critical role of routine immunization programs,” the study authors concluded. However, they did note that the findings were observational and could have been subject to healthy volunteer bias as well as influence from other unmeasured factors.
DISCLOSURE: For full disclosures of the study authors, visit bmj.com.
