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Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States

Jane J. Kim, PhD; Jesse Ortendahl, BS; and Sue J. Goldie, MD, MPH
[+] Article and Author Information

From Harvard School of Public Health, Boston, Massachusetts.


Acknowledgment: The authors thank the cervical cancer prevention team at the Center for Health Decision Science, Harvard School of Public Health, for their contributions.

Grant Support: By the National Cancer Institute (R01 CA93435), the Centers for Disease Control and Prevention, and the American Cancer Society, and also the Bill and Melinda Gates Foundation (30505) for related work in developing countries.

Potential Conflicts of Interest: None disclosed.

Reproducible Research Statement:Study protocol: Available from Dr. Kim (jkim@hsph.harvard.edu). Statistical code and data set: Not available.

Requests for Single Reprints: Jane J. Kim, PhD, Harvard School of Public Health, Department of Health Policy and Management, Center for Health Decision Science, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115; e-mail, jkim@hsph.harvard.edu.

Current Author Addresses: Drs. Kim and Goldie and Mr. Ortendahl: Harvard School of Public Health, Department of Health Policy and Management, Center for Health Decision Science, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115.

Author Contributions: Conception and design: J.J. Kim, J. Ortendahl, S.J. Goldie.

Analysis and interpretation of the data: J.J. Kim, J. Ortendahl, S.J. Goldie.

Drafting of the article: J.J. Kim.

Critical revision of the article for important intellectual content: J.J. Kim, J. Ortendahl, S.J. Goldie.

Final approval of the article: J.J. Kim, J. Ortendahl, S.J. Goldie.

Statistical expertise: J.J. Kim, J. Ortendahl.

Obtaining of funding: S.J. Goldie.

Administrative, technical, or logistic support: J. Ortendahl, S.J. Goldie.

Collection and assembly of data: J.J. Kim, J. Ortendahl.


Ann Intern Med. 2009;151(8):538-545. doi:10.7326/0003-4819-151-8-200910200-00007
Text Size: A A A

Background: Women older than 30 years are the main beneficiaries of improved cervical cancer screening with human papillomavirus (HPV) DNA testing. The role of vaccination against HPV types 16 and 18, which is recommended routinely for preadolescent girls, is unclear in this age group.

Objective: To assess the health and economic outcomes of HPV vaccination in older U.S. women.

Design: Cost-effectiveness analysis with an empirically calibrated model.

Data Sources: Published literature.

Target Population: U.S. women aged 35 to 45 years.

Time Horizon: Lifetime.

Perspective: Societal.

Intervention: HPV vaccination added to screening strategies that differ by test (cytology or HPV DNA testing), frequency, and start age versus screening alone.

Outcome Measures: Incremental cost-effectiveness ratios (2006 U.S. dollars per quality-adjusted life-year [QALY] gained).

Results of Base-Case Analysis: In the context of annual or biennial screening, HPV vaccination of women aged 35 to 45 years ranged from $116 950 to $272 350 per QALY for cytology with HPV DNA testing for triage of equivocal results and from $193 690 to $381 590 per QALY for combined cytology and HPV DNA testing, depending on age and screening frequency.

Results of Sensitivity Analysis: The probability of HPV vaccination being cost-effective for women aged 35 to 45 years was 0% with annual or biennial screening and less than 5% with triennial screening, at thresholds considered good value for money.

Limitation: The natural history of the disease and the efficacy of the vaccine in older women are uncertain.

Conclusion: Given currently available information, the effectiveness of HPV vaccination for women older than 30 years who are screened seems to be small. Compared with current screening that uses sensitive HPV DNA testing, HPV vaccination is associated with less attractive cost-effectiveness ratios in this population than those for other, well-accepted interventions in the United States.

Primary Funding Source: National Cancer Institute, Centers for Disease Control and Prevention, and the American Cancer Society.

Figures

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Figure 1.
Decision tree and cervical cancer natural history model.

Women older than 30 years who participate in the U.S. screening program may get vaccinated or continue with screening only. At the start of the analysis, women may reside in any of the mutually exclusive, collectively exhaustive health states denoted by the boxes. Incidence and progression of HPV infection, CIN 1, and CIN 2,3 depend on age and HPV type. Women with previous HPV infection face reduced risks for subsequent type-specific HPV infection because of natural immunity (dashed arrow). Not all health states and transitions are shown. CIN = cervical intraepithelial neoplasia (grade 1 or grade 2 or 3); HPV = human papillomavirus.

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Figure 2.
Cost-effectiveness of HPV vaccination of screened women, by screening algorithm.

Ratios for each strategy with vaccination are calculated compared with the corresponding screening strategy without vaccination. All ratios are expressed as cost, in 2006 U.S. dollars, per QALY. HPV = human papillomavirus; QALY = quality-adjusted life-year. Top. Ratios for HPV vaccination when screening involves cytology with HPV DNA testing for triage of equivocal results. Bottom. Ratios for HPV vaccination when screening involves a switch to combined cytology and HPV DNA testing after age 30 years.

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Appendix Figure 1.
Model fit to HPV prevalence.

HPV = human papillomavirus.

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Appendix Figure 2.
Model fit to HPV type distribution among women with CIN and invasive cancer.

CIN = cervical intraepithelial neoplasia (grade 1 or grade 2 or 3); HPV = human papillomavirus; HRo = other (non–HPV-16 or HPV-18) high-risk HPV types.

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Appendix Figure 3.
Model fit to cervical cancer incidence.
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Comments

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Cost-effectiveness of human papillomavirus vaccination
Posted on October 29, 2009
David Bishai
Johns Hopkins, Bloomberg School of Public Health
Conflict of Interest: None Declared

The article by Kim et al. offers an important contribution to our understanding of the cost implications of HPV control strategies in women over 30(1). It also offers lessons in the uses and potential misuses of cost-effectiveness estimates. The article adopted a societal perspective that many internists would be ill-advised to apply in their clinical practice. For this reason, some of the conclusions drawn by the article could be inapplicable to clinical decision-making. Our role as physicians is to advise our patients how to achieve health outcomes that they value given resource constraints. Physicians cannot ignore cost effectiveness, but given a patient centered perspective it would be a disservice to simply accept and apply the pronouncement that , "HPV vaccine does not represent good value for resources expended."

The paper used nothing more than informal heuristics to propel an assumption that society should not spend more than $100,000 per QALY. It is unlikely that this particular value applies to any particular individual consulting their physician about whether to receive an HPV vaccine. If we assume that individual patients' willingness to pay thresholds are normally distributed around $100,000 per QALY, then half of patients would happily pay out of their pocket for a vaccine that generated a $100,000 QALY and half would not. Our job as internists is to know our patients well enough to enable them to make decisions that are right for them. willingness to pay thresholds are normally distributed around $100,000 per QALY, then half of patients would happily pay out of their pocket for a vaccine that generated a $100,000 QALY and half would not. Our job as internists is to know our patients well enough to enable them to make decisions that are right for them.

There are decisions in health policy that naturally demand a societal decision. These decisions are typically about publicly shared resources, like permissible levels of air pollutants, or appropriate speed limits, where all must share in a common decision. Vaccination decisions can be individually titrated, and there is no compelling reason to deny technology and information about it to those willing to pay for their own vaccine.

There is an unfortunate precedent for mistaking the individual and societal perspective. An influential study in 1995 concluded that the polysaccharide meningococcal vaccine's ability to save lives at $1 million per life saved was not cost-effective(2). As a result, of it being declared "not cost-effective," physicians generally did not even discuss the presence of this vaccine to college-bound teens who were at heightened risk. A generation of youth missed an opportunity. Earlier this decade several states passed laws mandating counseling about the presence of a vaccine (3), it emerged that with physician guidance many patients reached an independent judgment that the benefits of meningococcal vaccine represented good value for their own out of pocket spending.

There is no compelling reason for the US population to be subjected to a one-size fits all decision on whether women over 30 can be protected from HPV with a vaccine. Instead, the results of this paper, can contribute to liberating discussions between doctors and patients on the value of health and how much money to devote to its pursuit.

References

1. 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(8):538-45.

2. Jackson LA, Schuchat A, Gorsky RD, Wenger JD. Should college students be vaccinated against meningococcal disease? A cost-benefit analysis. Am J Public Health. 1995;85(6):843-5.

3. Baltimore RS, Jenson HB. Meningococcal vaccine: new recommendations for immunization of college freshmen. Curr Opin Pediatr. 2001;13(1):47-50.

Conflict of Interest:

None declared

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Summary for Patients

Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States

The summary below is from the full report titled “Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States.” It is in the 20 October 2009 issue of Annals of Internal Medicine (volume 151, pages 538-545). The authors are J.J. Kim, J. Ortendahl, and S.J. Goldie.

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