Original Research7 January 2020
    Author, Article, and Disclosure Information
    Visual Abstract. Effectiveness and Cost-Effectiveness of HPV Vaccination Through Age 45

    In the United States, the vaccine against human papillomavirus is usually administered to girls and boys beginning just before the start of adolescence. Studies have shown that the vaccine prevents cancer and saves money when it is given this way. The U.S. Food and Drug Administration recently approved the vaccine for use in women and men up to age 45, and this article estimates the cost-effectiveness of the vaccine in these adults.

    Abstract

    Background:

    In the United States, the routine age for human papillomavirus (HPV) vaccination is 11 to 12 years, with catch-up vaccination through age 26 years for women and 21 years for men. U.S. vaccination policy on use of the 9-valent HPV vaccine in adult women and men is being reviewed.

    Objective:

    To evaluate the added population-level effectiveness and cost-effectiveness of extending the current U.S. HPV vaccination program to women aged 27 to 45 years and men aged 22 to 45 years.

    Design:

    The analysis used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), an individual-based transmission dynamic model of HPV infection and associated diseases, calibrated to age-specific U.S. data.

    Data Sources:

    Published data.

    Target Population:

    Women aged 27 to 45 years and men aged 22 to 45 years in the United States.

    Time Horizon:

    100 years.

    Perspective:

    Health care sector.

    Intervention:

    9-valent HPV vaccination.

    Outcome Measures:

    HPV-associated outcomes prevented and cost-effectiveness ratios.

    Results of Base-Case Analysis:

    The model predicts that the current U.S. HPV vaccination program will reduce the number of diagnoses of anogenital warts and cervical intraepithelial neoplasia of grade 2 or 3 and cases of cervical cancer and noncervical HPV-associated cancer by 82%, 80%, 59%, and 39%, respectively, over 100 years and is cost saving (vs. no vaccination). In contrast, extending vaccination to women and men aged 45 years is predicted to reduce these outcomes by an additional 0.4, 0.4, 0.2, and 0.2 percentage points, respectively. Vaccinating women and men up to age 30, 40, and 45 years is predicted to cost $830 000, $1 843 000, and $1 471 000, respectively, per quality-adjusted life-year gained (vs. current vaccination).

    Results of Sensitivity Analysis:

    Results were most sensitive to assumptions about natural immunity and progression rates after infection, historical vaccination coverage, and vaccine efficacy.

    Limitation:

    Uncertainty about the proportion of HPV-associated disease due to infections after age 26 years and about the level of herd effects from the current HPV vaccination program.

    Conclusion:

    The current HPV vaccination program is predicted to be cost saving. Extending vaccination to older ages is predicted to produce small additional health benefits and result in substantially higher incremental cost-effectiveness ratios than the current recommendation.

    Primary Funding Source:

    Centers for Disease Control and Prevention.

    References

    • 1. Centers for Disease Control and PreventionQuadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep2007;56 (No. RR-2). Google Scholar
    • 2. Centers for Disease Control and Prevention (CDC)Recommendations on the use of quadrivalent human papillomavirus vaccine in males—Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep2011;60:1705-8. [PMID: 22189893] MedlineGoogle Scholar
    • 3. U.S. Food and Drug Administration. FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old, 2018. FDA news release. Accessed at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622715.htm on 24 October, 2018. Google Scholar
    • 4. Stokley SJeyarajah JYankey Det alImmunization Services Division, National Center for Immunization and Respiratory Diseases, CDCHuman papillomavirus vaccination coverage among adolescents, 2007-2013, and postlicensure vaccine safety monitoring, 2006-2014—United States. MMWR Morb Mortal Wkly Rep2014;63:620-4. [PMID: 25055185] MedlineGoogle Scholar
    • 5. Reagan-Steiner SYankey DJeyarajah Jet alNational, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2014. MMWR Morb Mortal Wkly Rep2015;64:784-92. [PMID: 26225476] CrossrefMedlineGoogle Scholar
    • 6. Reagan-Steiner SYankey DJeyarajah Jet alNational, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep2016;65:850-8. [PMID: 27561081] doi:10.15585/mmwr.mm6533a4 CrossrefMedlineGoogle Scholar
    • 7. Walker TYElam-Evans LDSingleton JAet alNational, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2016. MMWR Morb Mortal Wkly Rep2017;66:874-882. [PMID: 28837546] doi:10.15585/mmwr.mm6633a2 CrossrefMedlineGoogle Scholar
    • 8. Chesson HWMeites EEkwueme DUet alCost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States. Vaccine2018;36:4362-4368. [PMID: 29887325] doi:10.1016/j.vaccine.2018.04.071 CrossrefMedlineGoogle Scholar
    • 9. Brisson MLaprise JFChesson HWet alHealth and economic impact of switching from a 4-valent to a 9-valent HPV vaccination program in the United States. J Natl Cancer Inst2016;108. [PMID: 26438574] doi:10.1093/jnci/djv282 CrossrefMedlineGoogle Scholar
    • 10. Laprise JFMarkowitz LEChesson HWet alComparison of 2-dose and 3-dose 9-valent human papillomavirus vaccine schedules in the United States: a cost-effectiveness analysis. J Infect Dis2016;214:685-8. [PMID: 27234416] doi:10.1093/infdis/jiw227 CrossrefMedlineGoogle Scholar
    • 11. Chesson HWLaprise JFBrisson Met alImpact and cost-effectiveness of 3 doses of 9-valent human papillomavirus (HPV) vaccine among US females previously vaccinated with 4-valent HPV vaccine. J Infect Dis2016;213:1694-700. [PMID: 26908738] doi:10.1093/infdis/jiw046 CrossrefMedlineGoogle Scholar
    • 12. Van de Velde NBoily MCDrolet Met alPopulation-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. J Natl Cancer Inst2012;104:1712-23. [PMID: 23104323] doi:10.1093/jnci/djs395 CrossrefMedlineGoogle Scholar
    • 13. Brisson MLaprise JFDrolet Met alComparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: a transmission-dynamic modeling study. Vaccine2013;31:3863-71. [PMID: 23830974] doi:10.1016/j.vaccine.2013.06.064 CrossrefMedlineGoogle Scholar
    • 14. Lairson DRFu SChan Wet alMean direct medical care costs associated with cervical cancer for commercially insured patients in Texas. Gynecol Oncol2017;145:108-113. [PMID: 28196673] doi:10.1016/j.ygyno.2017.02.011 CrossrefMedlineGoogle Scholar
    • 15. Fu SLairson DRChan Wet alMean medical costs associated with vaginal and vulvar cancers for commercially insured patients in the United States and Texas. Gynecol Oncol2018;148:342-348. [PMID: 29274828] doi:10.1016/j.ygyno.2017.12.019 CrossrefMedlineGoogle Scholar
    • 16. Deshmukh AAZhao HFranzini Let alTotal lifetime and cancer-related costs for elderly patients diagnosed with anal cancer in the United States. Am J Clin Oncol2018;41:121-127. [PMID: 26523440] doi:10.1097/COC.0000000000000238 CrossrefMedlineGoogle Scholar
    • 17. Lairson DRWu CFChan Wet alMedical care cost of oropharyngeal cancer among texas patients. Cancer Epidemiol Biomarkers Prev2017;26:1443-1449. [PMID: 28838945] doi:10.1158/1055-9965.EPI-17-0220 CrossrefMedlineGoogle Scholar
    • 18. Jacobson JJEpstein JBEichmiller FCet alThe cost burden of oral, oral pharyngeal, and salivary gland cancers in three groups: commercial insurance, Medicare, and Medicaid. Head Neck Oncol2012;4:15. [PMID: 22537712] doi:10.1186/1758-3284-4-15 CrossrefMedlineGoogle Scholar
    • 19. Chesson HWEkwueme DUSaraiya Met alEstimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine2012;30:6016-9. [PMID: 22867718] doi:10.1016/j.vaccine.2012.07.056 CrossrefMedlineGoogle Scholar
    • 20. Kim JJGoldie SJHealth and economic implications of HPV vaccination in the United States. N Engl J Med2008;359:821-32. [PMID: 18716299] doi:10.1056/NEJMsa0707052 CrossrefMedlineGoogle Scholar
    • 21. Schabert VFYe XInsinga RPet alFive-year routine cervical cancer screening rates and intervals in a US health plan. Curr Med Res Opin2008;24:2429-35. [PMID: 18662493] doi:10.1185/03007990802281671 CrossrefMedlineGoogle Scholar
    • 22. Elbasha EHDasbach EJInsinga RPModel for assessing human papillomavirus vaccination strategies. Emerg Infect Dis2007;13:28-41. [PMID: 17370513] CrossrefMedlineGoogle Scholar
    • 23. Henk HJInsinga RPSinghal PKet alIncidence and costs of cervical intraepithelial neoplasia in a US commercially insured population. J Low Genit Tract Dis2010;14:29-36. [PMID: 20040833] doi:10.1097/LGT.0b013e3181ac05e9 CrossrefMedlineGoogle Scholar
    • 24. Insinga RPGlass AGRush BBThe health care costs of cervical human papillomavirus–related disease. Am J Obstet Gynecol2004;191:114-20. [PMID: 15295351] CrossrefMedlineGoogle Scholar
    • 25. Beachler DCJenkins GSafaeian Met alNatural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis2016;213:1444-54. [PMID: 26690341] doi:10.1093/infdis/jiv753 CrossrefMedlineGoogle Scholar
    • 26. Burger EAKim JJSy Set alAge of acquiring causal human papillomavirus (HPV) infections: leveraging simulation models to explore the natural history of HPV-induced cervical cancer. Clin Infect Dis2017;65:893-899. [PMID: 28531261] doi:10.1093/cid/cix475 CrossrefMedlineGoogle Scholar
    • 27. Burger E, Kok ID, Groene E, et al. Leveraging simulation models to explore the natural history of cervical carcinogenesis: a CISNET comparative modeling analysis. Presented at 32nd International Papillomavirus Conference, Sydney, Australia, 2–6 October 2018. Google Scholar
    • 28. Laprise JF, Chesson HW, Drolet M, et al. The impact of human papillomavirus vaccination in the United States: insights from comparing mathematical model predictions and surveillance data. Presented at 32nd International Papillomavirus Conference, Sydney, Australia, 2–6 October 2018. Google Scholar
    • 29. Sanders GDRussell LBet alCost-Effectiveness in Health and Medicine. 2nd ed. New York: Oxford Univ Pr; 2016. Google Scholar
    • 30. Kim JJOrtendahl JGoldie SJCost-effectiveness of human papillomavirus vaccination and cervical cancer screening in women older than 30 years in the United States. Ann Intern Med2009;151:538-45. [PMID: 19841455] LinkGoogle Scholar
    • 31. Meites ESzilagyi PGChesson HWet alHuman papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep2019;68:698-702. [PMID: 31415491] doi:10.15585/mmwr.mm6832a3 CrossrefMedlineGoogle Scholar
    • 32. Drolet MLaprise JFBrotherton JMLet alThe impact of human papillomavirus catch-up vaccination in Australia: implications for introduction of multiple age cohort vaccination and postvaccination data interpretation. J Infect Dis2017;216:1205-1209. [PMID: 28968800] doi:10.1093/infdis/jix476 CrossrefMedlineGoogle Scholar
    • 33. Plummer MPeto JFranceschi SInternational Collaboration of Epidemiological Studies of Cervical CancerTime since first sexual intercourse and the risk of cervical cancer. Int J Cancer2012;130:2638-44. [PMID: 21702036] doi:10.1002/ijc.26250 CrossrefMedlineGoogle Scholar
    • 34. Rodríguez ACSchiffman MHerrero Ret alLongitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst2010;102:315-24. [PMID: 20157096] doi:10.1093/jnci/djq001 CrossrefMedlineGoogle Scholar
    • 35. Centers for Disease Control and Prevention. Millions of US women are not getting screened for cervical cancer. Accessed at www.cdc.gov/media/releases/2014/p1105-vs-cervical-cancer.html on 8 March 2018. Google Scholar
    • 36. Chao CSilverberg MJBecerra TAet alHuman papillomavirus vaccination and subsequent cervical cancer screening in a large integrated healthcare system. Am J Obstet Gynecol2017;216:151. [PMID: 27746152] doi:10.1016/j.ajog.2016.10.006 CrossrefMedlineGoogle Scholar