By Rebecca B. Perkins, MD, MSc

Associate Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston

Dr. Perkins reports no financial relationships relevant to this field of study.

SYNOPSIS: In this retrospective cohort study of women in Sweden, receipt of human papillomavirus vaccination prior to age 17 years was associated with an 88% decrease in cervical cancer, and vaccination at ages 17 to 30 years was associated with a 53% decrease in cervical cancer.

SOURCE: Lei J, Ploner A, Elfström KM, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med 2020;383:1340-1348.

Although human papillomavirus (HPV) vaccination has been demonstrated in clinical trials and real-world effectiveness data to decrease rates of precancerous lesions, definitive data indicating cancer prevention were lacking.1 In this study by Lei et al, national Swedish health and demographic registries were used to follow women and girls from 2006 to 2017. Individuals included in the analysis were those who were between the ages of 10 and 30 years at any time during the study period, had not received HPV vaccination or a diagnosis of cervical cancer prior to the study period, and had not immigrated to Sweden after Jan. 1, 2006 (to ensure that vaccination was not received elsewhere). Women were followed until they received a cancer diagnosis, died, emigrated from Sweden or were lost from the registry, received bivalent HPV vaccine (quadrivalent vaccine was standard-of-care), had their 31st birthday, or until Dec. 31, 2017. Researchers controlled for age at follow up, calendar year, and county of residence for individuals. Since many of those included were minors, researchers also controlled for parental characteristics. Girls and women contributed time to the unvaccinated arm until they either achieved one of the termination criteria listed earlier, or until they received their first dose of quadrivalent HPV vaccine, at which time they began to contribute data to the vaccinated arm of the analysis. Sensitivity analyses addressed birth cohort and the potential contributions of herd immunity. All women were eligible to participate in Sweden’s cervical cancer screening program, which begins at age 23 years, with triennial screening.

Data to assess the association between HPV vaccination and subsequent risk of invasive cervical cancer were contributed by 1,672,983 girls and women. Five hundred thirty-eight invasive cervical cancers were diagnosed among 1,145,112 unvaccinated women, a crude incidence rate of 5.27 per 100,000 person-years. In comparison, 19 cancers were diagnosed among 527,871 vaccinated women, a crude incidence rate of 0.73 per 100,000 person-years. After adjusting for age, county of residence, calendar year, and parental characteristics (including education, household income, mother’s country of birth, and maternal history of cervical precancer and cervical or other cancers), the incidence rate ratio of vaccinated women was 0.37, indicating a 63% reduction in cancer incidence. The reduction was profoundly influenced by age at vaccination, with a reduction of 88% for those vaccinated prior to age 17 years, compared to 53% for those vaccinated at ages 17 to 30 years. All differences were statistically significant.

COMMENTARY

This is the first population-based study to demonstrate reductions in cancer associated with HPV vaccination on an individual level. Prior studies have provided evidence toward this phenomenon. A Finnish study examining long-term follow-up in clinical trial participants and a U.S.-based study demonstrated a decrease in cervical cancer diagnoses in women ages 19 to 24 years following the introduction of HPV vaccination.2,3 HPV vaccination rates rose in Sweden during the study period, reaching 71% by 2015, although the authors did not find evidence of herd immunity regarding cervical cancer prevention.4

This study has several important findings. First, it notes a significant reduction of cervical cancer among women who are participating in an organized screening program, indicating an additive effect of vaccination above cervical cancer screening alone. The authors did not control for individual screening participation in the study. Most Swedish women (82%) participate in screening, and participation is associated with the socioeconomic factors used as controls in the study.5 This implies that cancer prevention from HPV vaccines could be even greater in areas where fewer women participate in screening. Another key finding of this study is the substantial improvement in cancer prevention when vaccination occurs prior to age 17 years compared to ages 17 to 30 years.

This underscores the importance of completing vaccination in adolescence as recommended by the Centers for Disease Control and Prevention, and also supports current catch-up recommendations to continue to vaccinate all individuals through age 26 years.6-8 As obstetrician-gynecologists, we can help reduce invasive cervical cancers by ensuring that our eligible patients ages 9 to 26 years receive vaccination, regardless of sexual activity, prior exposure to HPV, or sexual orientation.9 We also play a crucial role in educating our patients who are mothers about the importance of vaccinating their adolescent children. Vaccination in mid-adulthood, ages 27 to 45 years, is not routinely recommended since most individuals in this age group previously have been exposed to HPV. Providers may use shared decision-making on an individual patient basis, considering a patient’s risk of acquiring a new HPV infection in the future and whether vaccination may be beneficial.9

REFERENCES

  1. Drolet M, Benard E, Boily MC, et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: A systematic review and meta-analysis. Lancet Infect Dis 2015;15:565-580.
  2. Luostarinen T, Apter D, Dillner J, et al. Vaccination protects against invasive HPV-associated cancers. Int J Cancer 2018;142:2186-2187.
  3. 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.
  4. Grün N, Ährlund-Richter A, Franzén J, et al. Follow-up on oral and cervical human papillomavirus prevalence 2013–2015 in youth at a youth clinic in Stockholm, Sweden. Infect Dis (Lond) 2016;48:169-170.
  5. Hortlund M, Elfström KM, Sparén P, et al. Cervical cancer screening in Sweden 2014-2016. PLoS One 2018;13:e0209003.
  6. Petrosky E, Bocchini JA Jr, Hariri S, et al. Use of 9-valent human papillomavirus (HPV) vaccine: Updated HPV vaccination recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2015;64:300-304.
  7. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination — updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016;65:1405-1408.
  8. Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: Updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2019;68:698-702.
  9. American College of Obstetricians and Gynecologists’ Committee on Adolescent Health Care; and Immunization, Infectious Disease, and Public Health Preparedness Expert Work Group. Human Papillomavirus Vaccination: ACOG Committee Opinion, Number 809. Obstet Gynecol 2020;136:e15-e21.