By Rebecca B. Perkins, MD, MSc
Associate Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston
SYNOPSIS: This study evaluated the cost-effectiveness of extending the upper age limit of human papillomavirus (HPV) vaccination to age 30 to 45 years using two independent HPV microsimulation models and found that vaccinating in this age group was not cost-effective.
SOURCE: Kim JJ, Simms KT, Killen J, et al. Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis. PLoS Med 2021; Mar 11. doi.org/10.1371/journal.pmed.1003534
Human papillomavirus (HPV) vaccination is considered a powerful tool for cancer prevention. Clinical trials and long-term population-level follow-up studies have demonstrated decreases in precancers and cancers.1-3 However, these findings are based largely on HPV vaccination in adolescence, prior to exposure to oncogenic HPV types. Recently, HPV vaccination was given Food and Drug Administration approval for use in adults aged 26 to 45 years, and the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices recommended shared decision-making in this age group.4 The recommendation is based on study findings of a reduced composite endpoint for genital HPV disease among previously uninfected women, and notes that vaccination is not routinely recommended for this age group because of a lack of anticipated population-level benefit.4 The study by Kim et al describes the findings of two microsimulation models of HPV infection. In these models, which have been validated previously against several population-level datasets, individuals can move between states of no infection, infection, precancer, and cancer. HPV-related diseases in the models included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. The models compared the cost effectiveness of HPV vaccination in women through age 26 years and in men through age 21 years with vaccination through ages 30, 35, 40, and 45 years. Over a wide range of model assumptions and sensitivity analysis, HPV vaccination at older ages was not cost-effective. Incremental cost-effectiveness ratios (ICERs) ranged from $315,700 to $440,600 per quality-adjusted life year (QALY) gained, which exceeds the commonly accepted upper threshold of $200,000 per QALY. This supports current CDC recommendations not to routinely recommend HPV vaccination for this age group.
This study adds important evidence to help providers, patients, and policymakers decide when to discuss, accept, and reimburse HPV vaccination among patients aged 27 to 45 years. The effectiveness of HPV vaccination at preventing precancer and cancers declines in older adolescence, with several studies demonstrating significant drops in effectiveness after age 18.5,6 The people to most likely to benefit from HPV vaccination are those who have not been exposed to oncogenic HPV before, and are likely to be exposed in the future. This applies broadly to adolescents who have not yet begun sexual activity. However, since most people acquire HPV within a few years of beginning intercourse, relatively few adults are in this category.7-9 Primary care clinicians have many health maintenance topics that have clear benefits and are cost-effective, including cancer screenings, flu vaccination, smoking cessation, and cardiovascular disease prevention, to discuss with patients.10 This study supports current guidelines not to discuss HPV vaccination routinely with adult patients.4 Guidance is limited regarding which patients may benefit from HPV vaccination as adults. The American College of Obstetricians and Gynecologists (ACOG) supports CDC recommendations against routine vaccination. ACOG notes that the women most likely to benefit from vaccination include younger women, those not in committed monogamous relationships, and those recently diagnosed with sexually transmitted infections.11 One specific population that may benefit from HPV vaccination is patients who have been treated for cervical intraepithelial neoplasia, since data indicate that post-treatment vaccination may be beneficial to prevent recurrence.12,13 One meta-analysis found a 64% reduction in recurrence of cervical intraepithelial neoplasia grade 2 or higher.14 A randomized controlled trial in the Netherlands currently is exploring this question, which should provide more definitive data on whether vaccination should be routinely recommended after precancer treatment.15
- FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 2007;356:1915-1927.
- 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.
- 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.
- 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.
- Castle PE, Xie X, Xue X, et al. Impact of human papillomavirus vaccination on the clinical meaning of cervical screening results. Prev Med 2019;118:44-50.
- Gertig DM, Brotherton JM, Budd AC, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: A data linkage study. BMC Med 2013;11:227.
- Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: Incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003;157:218-226.
- Partridge JM, Hughes JP, Feng Q, et al. Genital human papillomavirus infection in men: Incidence and risk factors in a cohort of university students. J Infect Dis 2007;196:1128-1136.
- Burchell AN, Winer RL, de Sanjose S, Franco EL. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine 2006;24 Suppl 3:S3/52-61.
- U.S. Department of Health and Human Services. Healthy People 2030. https://health.gov/healthypeople
- [No authors listed]. Human papillomavirus vaccination: ACOG Committee Opinion, Number 809. Obstet Gynecol 2020;136:e15-e21.
- Petrillo M, Dessole M, Tinacci E, et al. Efficacy of HPV vaccination in women receiving LEEP for cervical dysplasia: A single institution’s experience. Vaccines (Basel) 2020;8:45.
- Bogani G, Raspagliesi F, Sopracordevole F, et al. Assessing the long-term role of vaccination against HPV after loop electrosurgical excision procedure (LEEP): A propensity-score matched comparison. Vaccines (Basel) 2020;8:717.
- Lichter K, Krause D, Xu J, et al. Adjuvant human papillomavirus vaccine to reduce recurrent cervical dysplasia in unvaccinated women: A systematic review and meta-analysis. Obstet Gynecol 2020;135:
- van de Laar RLO, Hofhuis W, Duijnhoven RG, et al. Adjuvant VACcination against HPV in surgical treatment of Cervical Intra-epithelial Neoplasia (VACCIN study) a study protocol for a randomised controlled trial. BMC Cancer 2020;20:539.