
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 Prevention . Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007;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 Rep. 2011;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 S ,Jeyarajah J ,Yankey D ,et al ;Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC . Human papillomavirus vaccination coverage among adolescents, 2007-2013, and postlicensure vaccine safety monitoring, 2006-2014—United States. MMWR Morb Mortal Wkly Rep. 2014;63:620-4. [PMID: 25055185] MedlineGoogle Scholar - 5.
Reagan-Steiner S ,Yankey D ,Jeyarajah J ,et al . National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:784-92. [PMID: 26225476] CrossrefMedlineGoogle Scholar - 6.
Reagan-Steiner S ,Yankey D ,Jeyarajah J ,et al . National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65:850-8. [PMID: 27561081] doi:10.15585/mmwr.mm6533a4 CrossrefMedlineGoogle Scholar - 7.
Walker TY ,Elam-Evans LD ,Singleton JA ,et al . National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2016. MMWR Morb Mortal Wkly Rep. 2017;66:874-882. [PMID: 28837546] doi:10.15585/mmwr.mm6633a2 CrossrefMedlineGoogle Scholar - 8.
Chesson HW ,Meites E ,Ekwueme DU ,et al . Cost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States. Vaccine. 2018;36:4362-4368. [PMID: 29887325] doi:10.1016/j.vaccine.2018.04.071 CrossrefMedlineGoogle Scholar - 9.
Brisson M ,Laprise JF ,Chesson HW ,et al . Health and economic impact of switching from a 4-valent to a 9-valent HPV vaccination program in the United States. J Natl Cancer Inst. 2016;108. [PMID: 26438574] doi:10.1093/jnci/djv282 CrossrefMedlineGoogle Scholar - 10.
Laprise JF ,Markowitz LE ,Chesson HW ,et al . Comparison of 2-dose and 3-dose 9-valent human papillomavirus vaccine schedules in the United States: a cost-effectiveness analysis. J Infect Dis. 2016;214:685-8. [PMID: 27234416] doi:10.1093/infdis/jiw227 CrossrefMedlineGoogle Scholar - 11.
Chesson HW ,Laprise JF ,Brisson M ,et al . Impact 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 Dis. 2016;213:1694-700. [PMID: 26908738] doi:10.1093/infdis/jiw046 CrossrefMedlineGoogle Scholar - 12.
Van de Velde N ,Boily MC ,Drolet M ,et al . Population-level impact of the bivalent, quadrivalent, and nonavalent human papillomavirus vaccines: a model-based analysis. J Natl Cancer Inst. 2012;104:1712-23. [PMID: 23104323] doi:10.1093/jnci/djs395 CrossrefMedlineGoogle Scholar - 13.
Brisson M ,Laprise JF ,Drolet M ,et al . Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: a transmission-dynamic modeling study. Vaccine. 2013;31:3863-71. [PMID: 23830974] doi:10.1016/j.vaccine.2013.06.064 CrossrefMedlineGoogle Scholar - 14.
Lairson DR ,Fu S ,Chan W ,et al . Mean direct medical care costs associated with cervical cancer for commercially insured patients in Texas. Gynecol Oncol. 2017;145:108-113. [PMID: 28196673] doi:10.1016/j.ygyno.2017.02.011 CrossrefMedlineGoogle Scholar - 15.
Fu S ,Lairson DR ,Chan W ,et al . Mean medical costs associated with vaginal and vulvar cancers for commercially insured patients in the United States and Texas. Gynecol Oncol. 2018;148:342-348. [PMID: 29274828] doi:10.1016/j.ygyno.2017.12.019 CrossrefMedlineGoogle Scholar - 16.
Deshmukh AA ,Zhao H ,Franzini L ,et al . Total lifetime and cancer-related costs for elderly patients diagnosed with anal cancer in the United States. Am J Clin Oncol. 2018;41:121-127. [PMID: 26523440] doi:10.1097/COC.0000000000000238 CrossrefMedlineGoogle Scholar - 17.
Lairson DR ,Wu CF ,Chan W ,et al . Medical care cost of oropharyngeal cancer among texas patients. Cancer Epidemiol Biomarkers Prev. 2017;26:1443-1449. [PMID: 28838945] doi:10.1158/1055-9965.EPI-17-0220 CrossrefMedlineGoogle Scholar - 18.
Jacobson JJ ,Epstein JB ,Eichmiller FC ,et al . The cost burden of oral, oral pharyngeal, and salivary gland cancers in three groups: commercial insurance, Medicare, and Medicaid. Head Neck Oncol. 2012;4:15. [PMID: 22537712] doi:10.1186/1758-3284-4-15 CrossrefMedlineGoogle Scholar - 19.
Chesson HW ,Ekwueme DU ,Saraiya M ,et al . Estimates of the annual direct medical costs of the prevention and treatment of disease associated with human papillomavirus in the United States. Vaccine. 2012;30:6016-9. [PMID: 22867718] doi:10.1016/j.vaccine.2012.07.056 CrossrefMedlineGoogle Scholar - 20.
Kim JJ ,Goldie SJ . Health and economic implications of HPV vaccination in the United States. N Engl J Med. 2008;359:821-32. [PMID: 18716299] doi:10.1056/NEJMsa0707052 CrossrefMedlineGoogle Scholar - 21.
Schabert VF ,Ye X ,Insinga RP ,et al . Five-year routine cervical cancer screening rates and intervals in a US health plan. Curr Med Res Opin. 2008;24:2429-35. [PMID: 18662493] doi:10.1185/03007990802281671 CrossrefMedlineGoogle Scholar - 22.
Elbasha EH ,Dasbach EJ ,Insinga RP . Model for assessing human papillomavirus vaccination strategies. Emerg Infect Dis. 2007;13:28-41. [PMID: 17370513] CrossrefMedlineGoogle Scholar - 23.
Henk HJ ,Insinga RP ,Singhal PK ,et al . Incidence and costs of cervical intraepithelial neoplasia in a US commercially insured population. J Low Genit Tract Dis. 2010;14:29-36. [PMID: 20040833] doi:10.1097/LGT.0b013e3181ac05e9 CrossrefMedlineGoogle Scholar - 24.
Insinga RP ,Glass AG ,Rush BB . The health care costs of cervical human papillomavirus–related disease. Am J Obstet Gynecol. 2004;191:114-20. [PMID: 15295351] CrossrefMedlineGoogle Scholar - 25.
Beachler DC ,Jenkins G ,Safaeian M ,et al . Natural acquired immunity against subsequent genital human papillomavirus infection: a systematic review and meta-analysis. J Infect Dis. 2016;213:1444-54. [PMID: 26690341] doi:10.1093/infdis/jiv753 CrossrefMedlineGoogle Scholar - 26.
Burger EA ,Kim JJ ,Sy S ,et al . Age of acquiring causal human papillomavirus (HPV) infections: leveraging simulation models to explore the natural history of HPV-induced cervical cancer. Clin Infect Dis. 2017;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 GD ,Russell LB ,et al . Cost-Effectiveness in Health and Medicine. 2nd ed. New York: Oxford Univ Pr; 2016. Google Scholar - 30.
Kim JJ ,Ortendahl J ,Goldie SJ . Cost-effectiveness of human papillomavirus vaccination and cervical cancer screening in women older than 30 years in the United States. Ann Intern Med. 2009;151:538-45. [PMID: 19841455] LinkGoogle Scholar - 31.
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. [PMID: 31415491] doi:10.15585/mmwr.mm6832a3 CrossrefMedlineGoogle Scholar - 32.
Drolet M ,Laprise JF ,Brotherton JML ,et al . The impact of human papillomavirus catch-up vaccination in Australia: implications for introduction of multiple age cohort vaccination and postvaccination data interpretation. J Infect Dis. 2017;216:1205-1209. [PMID: 28968800] doi:10.1093/infdis/jix476 CrossrefMedlineGoogle Scholar - 33.
Plummer M ,Peto J ,Franceschi S ;International Collaboration of Epidemiological Studies of Cervical Cancer . Time since first sexual intercourse and the risk of cervical cancer. Int J Cancer. 2012;130:2638-44. [PMID: 21702036] doi:10.1002/ijc.26250 CrossrefMedlineGoogle Scholar - 34.
Rodríguez AC ,Schiffman M ,Herrero R ,et al . Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. J Natl Cancer Inst. 2010;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 C ,Silverberg MJ ,Becerra TA ,et al . Human papillomavirus vaccination and subsequent cervical cancer screening in a large integrated healthcare system. Am J Obstet Gynecol. 2017;216:151. [PMID: 27746152] doi:10.1016/j.ajog.2016.10.006 CrossrefMedlineGoogle Scholar
Author, Article, and Disclosure Information
Jean-François Laprise,
Centre de recherche du CHU de Québec–Université Laval, Québec City, Québec, Canada (J.L., M.D., D.M., É.B.)
Centers for Disease Control and Prevention, Atlanta, Georgia (H.W.C., L.E.M.)
Centre de recherche du CHU de Québec–Université Laval and Département de médecine sociale et préventive, Université Laval, Québec City, Québec, Canada and Imperial College, London, United Kingdom (M.B.)
Note: The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.
Financial Support: By a contract from the CDC (00HCVGEB-2018-25176), a Fonds de recherche du Québec–Santé (FRQS) Research Scholars award (to M. Brisson), and a foundation scheme grant from the Canadian Institutes of Health Research (FDN-143283). This research was enabled in part by support provided by WestGrid (www.westgrid.ca), Compute Ontario (www.computeontario.ca), and Compute Canada (www.computecanada.ca).
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1182.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: A protocol was not published before initiation of the study. The article, Supplement, and technical appendix publicly available on Dr. Brisson's Web site (www.marc-brisson.net/HPVadvise-US.pdf) are designed to provide sufficient information for an interested reader to replicate the analysis. Statistical code: Not applicable. Data set: Not applicable; this study did not use an analytic data set but used simulated data generated via our model, HPV-ADVISE.
Corresponding Author: Marc Brisson, PhD, Centre de recherche du CHU de Québec, Axe Santé des populations et pratiques optimales en santé Québec, Hôpital du Saint-Sacrement, 1050 Chemin Sainte-Foy, Québec G1S 4L8, Canada; e-mail, marc.
Current Author Addresses: Drs. Laprise, Drolet, Martin, and Brisson, and Ms. Bénard: Centre de recherche du CHU de Québec, Axe Santé des populations et pratiques optimales en santé Québec, Hôpital du Saint-Sacrement, 1050 Chemin Sainte-Foy, Québec G1S 4L8, Canada.
Dr. Chesson: Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Mailstop US12-3, 1600 Clifton Road, Atlanta, GA 30329.
Dr. Markowitz: Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Mailstop H24-5, 1600 Clifton Road, Atlanta, GA 30329.
Author Contributions: Conception and design: M. Brisson, H.W. Chesson, L.E. Markowitz.
Analysis and interpretation of the data: J.F. Laprise, H.W. Chesson, L.E. Markowitz, M. Drolet, D. Martin, É. Bénard, M. Brisson.
Drafting of the article: J.F. Laprise.
Critical revision for important intellectual content: J.F. Laprise, H.W. Chesson, L.E. Markowitz, M. Drolet, D. Martin, É. Bénard, M. Brisson.
Final approval of the article: J.F. Laprise, H.W. Chesson, L.E. Markowitz, M. Drolet, D. Martin, É. Bénard, M. Brisson.
Obtaining of funding: M. Brisson.
Administrative, technical, or logistic support: J.F. Laprise, L.E. Markowitz, M. Drolet.
Collection and assembly of data: J.F. Laprise, H.W. Chesson, L.E. Markowitz, M. Drolet, M. Brisson.
This article was published at Annals.org on 10 December 2019.
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