HPV vaccination associated with substantial lower invasive cervical cancer risk

1. Quadrivalent human papillomavirus (HPV) vaccination was associated with a substantial lower risk of invasive cervical cancer in Swedish girls and women 10 to 30 years of age.

2. HPV vaccination at a younger age was associated with a more distinct reduction in the incidence of invasive cervical cancer.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Sweden approved a national immunization program for human papillomavirus (HPV) vaccines in 2006, which covers HPV types 6, 11, 16, and 18. HPV vaccination is shown to protect against HPV infection, genital warts, and high grade precancerous cervical lesions. However, the vaccination’s ultimate goal is to prevent invasive cervical cancer, which has yet to be determined. As such, this study utilized a nationwide registry from Sweden to analyze the association between HPV vaccination and invasive cervical cancer risk. The study results demonstrated HPV vaccination was associated with a substantial reduction in invasive cervical cancer risk. The prospective study was limited by the inability to account for confounding lifestyle and health factors of the participants. HPV-vaccinated women could generally be healthier than unvaccinated women resulting in a healthy volunteer selection bias. Therefore, the participants who had the HPV vaccination may also not smoke and use oral contraceptives, which mitigated their risk for invasive cervical cancer unrelated to the vaccine. Nonetheless, this study’s results are significant, and its findings underscore the ultimate benefit of the HPV vaccine.

Click to read the study in NEJM

Relevant Reading: Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

In-Depth [prospective cohort]: This prospective cohort study included 1,672,983 participants from Sweden. Participants included in the study were between the ages of 10 to 30 years, had no previous HPV vaccination, and had no previous invasive cervical cancer. Participants with a diagnosis of invasive cervical cancer before January 1, 2006, or had immigrated to Sweden after January 1, 2006, were excluded from this study. The participants were followed starting on their 10^th birthday or January 1, 2006, whichever came later. All participants were followed until they received a diagnosis of invasive cervical cancer, received bivalent HPV vaccination, had their 31^st birthday, or until December 31, 2017, whichever came first. The vaccinated cohort (n=527,871 participants) was compared to an unvaccinated cohort (n=1,145,112 participants) – the control group. The primary end point was the cumulative incidence of cervical cancer. Within the vaccinated cohort, 438,939 (83.2%) of participants initiated their vaccination prior to the age 17 years. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons by 30 years of age in the vaccinated group compared to 94 cases per 100,000 persons in the unvaccinated group. After adjusting for age, the incidence rate ratio for cervical cancer between vaccinated and unvaccinated participants was 0.51 (95% confidence interval [CI], 0.32 to 0.82). Upon further stratification by age, the cumulative incidence for participants who had initiated vaccination prior to the age of 17 years was 4 cases per 100,000 persons compared to 54 cases per 100,000 persons for the participants who had initiated vaccination between the age of 17 to 30 years. The incidence rate ratio for participants who had been vaccinated before the age of 17 years was 0.12 (95% CI, 0.00 to 0.34). Furthermore, the incidence rate ratio for participants who had been vaccinated between 17 to 30 years of age was 0.47 (95% CI, 0.27 to 0.75). Taken together, HPV vaccination was associated with a lower risk of invasive cervical cancer with a distinct reduction in incidence when the vaccine was initiated before the age of 17 years.

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