By Rebecca B. Perkins, MD, MSc
Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston
SYNOPSIS: This long-term follow-up study of three cluster-randomized trials of human papillomavirus (HPV) vaccination evaluated cancer protection over up to 11 years of follow-up. During this time, 17 HPV-positive cancers were identified in the unvaccinated group, and 0 were identified in the vaccinated group, indicating 100% vaccine efficacy at preventing HPV-associated cancers.
SOURCE: Lehtinen M, et al. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: Population-based follow-up of a cluster-randomised trial. BMJ Open 2021;11:e050669.
Human papillomavirus (HPV) infection is associated with six types of human cancers, as well as pregnancy complications, including preterm delivery.1-4 HPV vaccination has been recommended in more than 180 countries since 2006.5 Countries with high vaccination rates already have noted decreases in HPV prevalence, cervical precancers, and cervical cancers.6-8 A study from Australia also indicates reductions in preterm births and small for gestational age infants as women vaccinated as adolescents begin to make up the majority of the pregnant population.9 Because HPV vaccination is recommended in early adolescence, more than a decade before most HPV exposures, concerns have been raised about duration of protection. In addition, the clinical trials were based on prevention of precancers, but did not have cancer outcomes.10
The study by Lehtinen et al examines the development of invasive cancers among randomized cohorts of Phase III clinical trials of bivalent and quadrivalent HPV vaccines.11 A total of 3,341 vaccinated women and 16,536 unvaccinated controls were followed by the Finnish Cancer Registry starting at trial cessation in either 2007 or 2009. Women were followed for the development of invasive cancer through 2019. Over 11 years of follow-up, a total of 17 HPV-positive cancers were identified, including 14 cervical, one vaginal, one vulvar, and one tongue cancer. All cancers occurred in unvaccinated women; none occurred in the vaccinated group. Intention-to-treat vaccine efficacy was estimated at 100% (P < 0.05).
COMMENTARY
This study indicates HPV vaccination confers long-term protection against a variety of HPV-related cancers. In the United States alone, nearly 44,000 HPV-associated cancers are diagnosed annually.12 The majority of these could be prevented with HPV vaccination in adolescence.3 However, HPV vaccination rates in the United States remain below national goals, and also are lower than rates for the other adolescent vaccines: tetanus-diphtheria-pertussis and meningococcus.13,14 Furthermore, adolescent vaccination, particularly HPV vaccination, decreased substantially during the COVID pandemic.15
Vaccine misinformation and anti-vaccination sentiment increased in prominence over the past decade, and the volume of misinformation has accelerated during the COVID-19 pandemic. The World Health Organization cites vaccine hesitancy as one of the top 10 threats to global health.16 The rise of social media has led to rapid promulgation of anti-vaccine misinformation through popular sites such as Facebook, YouTube, and WhatsApp.17-19 Unfortunately, public health messaging has not reached the same sophistication or success as anti-vaccine messaging. In fact, public health messages intended to educate on vaccine importance may unintentionally reinforce negative beliefs.20,21
Nonetheless, healthcare providers remain the most trusted source of vaccine information, and recommendations by healthcare providers are the strongest predictors of vaccine acceptance.22-24 To protect today’s adolescents from HPV-associated cancers in adulthood, it is incumbent upon all healthcare providers to ensure parents and adolescents receive high-quality vaccine recommendations. Yet, continuing to combat misinformation can be fatiguing to healthcare providers and lead to burnout.25 The data from Lehtinen et al that HPV vaccination prevented all HPV-associated cancers more than a decade after vaccine receipt may be motivating for both clinicians and parents.
REFERENCES
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- Jemal A, et al. Annual report to the nation on the status of cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 2013;105:175-201.
- Saraiya M, et al. US assessment of HPV types in cancers: Implications for current and 9-valent HPV vaccines. J Natl Cancer Inst 2015;107:djv086.
- Niyibizi J, et al. Association between maternal human papillomavirus infection and adverse pregnancy outcomes: Systematic review and meta-analysis. J Infect Dis 2020;221:1925-1937.
- World Health Organization. Human papillomavirus vaccines (HPV). https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/human-papillomavirus-vaccines-(HPV)
- Oliver SE, et al. Prevalence of human papillomavirus among females after vaccine introduction-National Health and Nutrition Examination Survey, United States, 2003-2014. J Infect Dis 2017;216:594-603.
- McClung NM, et al. Estimated number of cases of high-grade cervical lesions diagnosed among women – United States, 2008 and 2016. MMWR Morb Mortal Wkly Rep 2019;68:337-343.
- Lei J, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med 2020;383:1340-1348.
- Yuill S, et al. Has human papillomavirus (HPV) vaccination prevented adverse pregnancy outcomes? Population-level analysis after 8 years of a national HPV vaccination program in Australia. J Infect Dis 2020;222:499-508.
- FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927.
- Lehtinen M, et al. Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: Population-based follow-up of a cluster-randomised trial. BMJ Open 2021;11:e050669.
- Senkomago V, et al. Human papillomavirus-attributable cancers – United States, 2012-2016. MMWR Morb Mortal Wkly Rep 2019;68:724-728.
- U.S. Department of Health and Human Services. Healthy People 2030. https://health.gov/healthypeople
- Pingali C, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years – United States, 2020. MMWR Morb Mortal Wkly Rep 2021;70:1183-1190.
- Saxena K, et al. Impact of the COVID-19 pandemic on adolescent vaccinations: Projected time to reverse deficits in routine adolescent vaccination in the United States. Curr Med Res Opin 2021;37:2077-2087.
- World Health Organization. Ten threats to global health in 2019. https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019
- Gu J, et al. The impact of Facebook’s vaccine misinformation policy on user endorsements of vaccine content: An interrupted time series analysis. Vaccine 2022; Mar 1:S0264-410X(22)00209-2. doi:10.1016/j.vaccine.2022.02.062. [Online ahead of print].
- Li HOY, et al. YouTube as a source of misinformation on COVID-19 vaccination: A systematic analysis. BMJ Glob Health 2022;7:e008334.
- Yeung AWK, et al. Medical and health-related misinformation on social media: Bibliometric study of the scientific literature. J Med Internet Res 2022;24:e28152.
- Nyhan B, et al. Effective messages in vaccine promotion: A randomized trial. Pediatrics 2014;133:e835-842.
- Pluviano S, et al. Misinformation lingers in memory: Failure of three pro-vaccination strategies. PLoS One 2017;12:e0181640.
- Chung Y, et al. Influences on immunization decision-making among US parents of young children. Matern Child Health J 2017;21:2178-2187.
- Fenton AT, et al. Indicated or elective? The association of
providers’ words with HPV vaccine receipt. Hum Vaccin Immunother 2018;14:2503-2509.
- Eun TJ, et al. Relative contributions of parental intention and provider recommendation style to HPV and meningococcal vaccine receipt. Hum Vaccin Immunother 2019;15:2460-2465.
- McClure CC, et al. Vaccine hesitancy: Where we are and where we are going. Clin Ther 2017;39:1550-1562.
