HPV vaccination and the risk of invasive cervical cancer
Quote this article as:
J Lei, A Ploner, P Sparén (March 2022). HPV vaccination and the risk of invasive cervical cancer. www.HPVWorld.com, 192
Human papillomavirus (HPV) vaccines have been available since 2006. Quadrivalent HPV (qHPV) vaccine has been demonstrated to offer effective protection against HPV infection, genital warts and high-grade precancerous cervical lesions.1,2 In Finland, follow-up of participants in HPV vaccine trials showed no HPV-related cancers in vaccinated women compared to 10 cases of HPV-related cancer in unvaccinated women.3 A study from the United States showed significantly lower incidence of cervical cancer among girls and women 15 to 34 years of age during the post-vaccination period compared to the pre-vaccination period.4 However, population-based studies examining the association between HPV vaccine and invasive cervical cancer on an individual level are lacking.
In Sweden, HPV vaccines were introduced in 2006. Starting from May 2007, HPV vaccines were subsidized for girls aged 13-17. A free-of-charge school-based vaccination program for girls aged 10-12 together with a catch-up vaccination program for girls aged 13-18 was launched in January 2012. Since 2016, those who did not vaccinate through the school-based program were offered another chance to be vaccinated up to age 18 following a three-dose vaccination plan. The Swedish guidelines were updated according to the World Health Organization (WHO) recommendations and the school-based program began to use a two-dose vaccination schedule for girls 10-12 (grade 5 and 6) in 2015.
In our study published in the New England Journal of Medicine,5 we used Swedish nationwide registers and followed a total of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. Among all included individuals, 527,871 were HPV-vaccinated with at least one dose of the qHPV vaccine. Among all vaccinated individuals included in the study, 438,939 (83.2%) initiated vaccination before age 17. We evaluated girls and women for cervical cancer until their 31st birthday, and assessed the association between HPV vaccination and the risk of invasive cervical cancer by comparing the incidence of cervical cancer in vaccinated vs. unvaccinated girls and women. We also stratified the vaccinated girls by age at vaccination initiation, using ages 17 and 20 as cut-off for this comparison. We account for confounding factors including age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother’s country of birth, and maternal disease history in the comparison.
During the follow-up period, we observed a total of 19 invasive cervical cancer cases among the vaccinated women, and 538 cases among the unvaccinated women. Figure 1 shows the cumulative incidence among unvaccinated women increasing sharply to 94 cases per 100,000 persons by age 30; among women initiating vaccination between ages 17 to 30, cumulative incidence was 54 cases per 100,000 persons by age 30; and among women initiating vaccination before age 17, cumulative incidence was 4 cases per 100,000 persons by age 28. Overall, this corresponds to a 63% lower risk of invasive cervical cancer associated with HPV vaccination in Swedish girls and women 10 to 30 years old (Table 1). Girls vaccinated before age 17 reduced their risk of invasive cervical cancer by 88%, and women vaccinated between age 17 and 30 reduced their risk of cervical cancer by 53% compared to unvaccinated women. All data in our study were retrieved from routinely collected, nationwide, high-quality Swedish registries, and consequently reflect the association between HPV vaccination and incidence of cervical cancer in a real-world setting.
In conclusion, qHPV vaccination is associated with substantially reduced risk of invasive cervical cancer at population level, especially for girls who initiate the vaccination at younger age. Our results highlight the significance of HPV vaccination in reducing risk of cervical cancer, and strongly support the importance to scale-up the coverage of HPV vaccination, especially in children and adolescents, in accordance with the WHO’s global strategy to accelerate the elimination of cervical cancer as a public health problem. Vaccinating at younger age is important in achieving maximum benefit for HPV vaccination and reducing the burden of cervical cancer, as vaccination has no therapeutic effect against pre-existing HPV infection.
CONFLICT OF INTERESTS
The authors declare no conflict of interests.
References
1. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane database of systematic reviews. 2018(5). Available from: https://doi.org/10.1002/14651858.cd009069.pub3
2. Drolet M, Bénard É, Pérez N, Brisson M. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet 2019;394:497-509. Available from: https://doi.org/10.1016/s0140-6736(19)30298-3
3. Luostarinen T, Apter D, Dillner J, et al. Vaccination protects against invasive HPV-associated cancers. Int J Cancer 2018;142:2186-7. Available from: https://doi.org/10.1002/ijc.31231
4. Guo F, Cofie LE, Berenson AB. Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction. Am J Prev Med 2018;55:197-204. Available from: https://doi.org/10.1016/j.amepre.2018.03.013
5. Lei J, Ploner A, Elfström KM, et al. HPV vaccination and the risk of invasive cervical cancer. New England Journal of Medicine. 2020 Oct 1;383(14):1340-8. Available from: https://doi.org/10.1056/nejmoa1917338
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