Cost-effectiveness of human papillomavirus vaccination and cervical cancer screening in women older than 30 years in the United States

Abstract

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.

Figure 1. Schematic of Decision Tree and Cervical Cancer Natural History Model

Women over age 30 (i.e., ages 35, 40, or 45) who participate in the U.S. screening program are faced with the decision to get vaccinated or continue with screening only. HPV vaccination (pink box) involves full adherence to the three-dose series at ages 35, 40, or 45 and provides complete, lifelong protection against incidence of vaccine-targeted HPV types among women without prior history of those types at vaccination. Screening (blue box) involves detection of precancerous lesions that can be treated before development of invasive cancer and may vary by test (i.e., cytology with HPV DNA testing as triage for equivocal results, with or without a switch to combined cytology and HPV DNA testing) and frequency (i.e., 1- to 5-year screening). 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 and cervical intraepithelial neoplasia, grade 1 (CIN 1) and grade 2,3 (CIN 2,3) depend on age and HPV type, categorized as type 16, type 18, other high-risk types, and low-risk types. Women who clear their infections or lesions are noted as having a history of prior HPV infection and face reduced risks of subsequent type-specific HPV infection due to natural immunity. Cancer states are stratified by stage (i.e., local, regional, distant) and detection status (i.e., undetected, symptom-detected, screen-detected). Death can occur from all-cause mortality from every health state and excess cancer-specific mortality from cancer states. Note, not all health states and transitions are shown.

Figure 2. Cost-Effectiveness of HPV-16,-18 Vaccination of Screened Women and Specific Screening Algorithm

Bars indicate the incremental cost-effectiveness ratios of adding HPV-16,-18 vaccination to cervical cancer screening for women who are 35, 40, and 45 years of age, when screening involves cytology with HPV DNA testing for triage of equivocal results, with no switch (top) and with a switch to combined cytology and HPV DNA testing after age 30 (bottom). Red represents the strategy of HPV vaccination in the context of annual screening; green, current screening; blue, biennial screening. Current screening assumes that among women who have ever been screened, 53% are screened annually, 17% every two years, 11% every three years, and 15% every five years (–31). Ratios for each vaccination strategy are calculated compared to the corresponding screening strategy without vaccination; for example, HPV vaccination in the context of biennial screening for 40-year-old women is compared with biennial screening without vaccination for 40-year-old women. All ratios are expressed as cost per quality-adjusted life year ($ per QALY). All costs are expressed in 2006 U.S. dollars.