HPV vaccination substantially protects against invasive cervical cancer

Quadrivalent human papillomavirus (HPV) vaccination can substantially reduce the risk of invasive cervical cancer, by up to almost 90 percent in women who were vaccinated early, a large Swedish registry-based study has shown.    

“Although the efficacy and effectiveness of the HPV vaccination against HPV infection, genital warts, and high-grade cervical lesions (CIN2+ and CIN3+) have been established, our results extend this knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer — which is the ultimate intent of HPV vaccination programmes,” they pointed out.

Typically, there is a long lead time — spanning 5 to 20 years — before cervical cancer develops after persistent HPV infection. “Therefore, randomized, controlled trials cannot readily evaluate vaccine effectiveness against invasive cervical cancer,” they explained.

“This is the first time that we, on a population level, are able to show that HPV vaccination is protective not only against cellular changes that can be precursors to cervical cancer but also against actual invasive cervical cancer,” said lead author Dr Lei Jiayao Karolinska Institutet in Solna, Sweden.

Using data from nationwide Swedish health registers, the researchers followed over a million (n=1,672,983) girls and women aged 10–30 years for the occurrence of incident cervical cancer. [N Engl J Med 2020;383:1340-1348]

During the study period, cervical cancer occurred in 19 women who had been vaccinated (0.004 percent) compared with 538 women who had not (0.05 percent).

The cumulative incidence rate of cervical cancer among vaccinated women was substantially lower than those who were never vaccinated (47 vs 94 cases per 100,000 persons).

After adjusting for age, women who had been vaccinated were half as likely to develop invasive cervical cancer compared with those who had not been vaccinated (incidence rate ratio [IRR], 0.51, 95 percent confidence interval [CI], 0.32–0.82).

Additional adjustment for other covariates including maternal birth country and history of CIN3+ or other cancers, parental education level, and annual household income further drove the IRR down to 0.37 (95 percent CI, 0.21–0.57).

When the analysis was stratified by age at vaccination, the protective benefit against invasive cervical cancer was greater in women who were vaccinated before the age of 17 years (IRR, 0.12, 95 percent CI, 0.00–0.34) compared with women who received vaccination between the age of 17–30 years (IRR, 0.47, 95 percent CI, 0.27–0.75).

“Our results support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit, since vaccination has no therapeutic effect against pre-existing HPV infection,” said Lei and co-authors.

The greater risk reduction seen when vaccination was initiated at a younger age was consistent with previous studies, which have shown that the risk of high-grade cervical lesions and genital warts was lower with HPV vaccination.

“Our data also strongly supports continuing HPV vaccinations of children and adolescents through national vaccination programmes,” said study co-author Professor Pär Sparén, also from Karolinska Institute.