Effectiveness and Cost-Effectiveness of Human Papillomavirus Vaccination Through Age 45 Years in the United States

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.

Figure 1.

Percent age of change in incidence under the current U.S. HPV vaccine recommendation and extended vaccination of women and men up to age 45 years for different outcomes. Base-case assumptions. The term cases prevented refers to the number of cases prevented in the United States over 100 years. Model predictions are represented as the median of the 50 best-fitting parameter sets. CIN2/3 = cervical intraepithelial neoplasia grade 2 or 3; HPV = human papillomavirus. A. Anogenital wart diagnoses (vertical lines between the curves represent the incremental benefit between the 2 strategies). B. Diagnosed CIN2/3. C. Cervical cancer. D. Noncervical HPV-associated cancer.

Figure 1.

Percent age of change in incidence under the current U.S. HPV vaccine recommendation and extended vaccination of women and men up to age 45 years for different outcomes. Base-case assumptions. The term cases prevented refers to the number of cases prevented in the United States over 100 years. Model predictions are represented as the median of the 50 best-fitting parameter sets. CIN2/3 = cervical intraepithelial neoplasia grade 2 or 3; HPV = human papillomavirus. A. Anogenital wart diagnoses (vertical lines between the curves represent the incremental benefit between the 2 strategies). B. Diagnosed CIN2/3. C. Cervical cancer. D. Noncervical HPV-associated cancer.

Figure 2.

Cost-effectiveness acceptability curves: percentage of the parameter sets in which the estimated incremental cost per QALY gained by mid-adult vaccination (vs. current vaccination) is equal to or less than a given cost per QALY–gained threshold. We separated the 50 parameter sets into those with lower probability of natural immunity after clearance in women (≤40% vs. >40%) and faster progression to CIN1/2/3 (e.g., average median time from infection to CIN1, 10 vs. 15 months; average median time from infection to CIN3, 32 vs. 36 months) (22 of 50 parameter sets) and those with higher natural immunity and slower progression (28 of 50 parameter sets). CIN1/2/3 = cervical intraepithelial neoplasia of grade 1, 2, or 3; QALY = quality-adjusted life-year. Top. Base-case analysis for all age scenarios of vaccination in mid-adult women and men. Bottom. Sensitivity analysis of natural history parameters for vaccination through age 30 years.