Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16,18 vaccination

Abstract

Background: The availability of human papillomavirus (HPV) DNA testing and vaccination against HPV types 16 and 18 (HPV-16,18) motivates questions about the cost-effectiveness of cervical cancer prevention in the United States for unvaccinated older women and for girls eligible for vaccination.

Methods: An empirically calibrated model was used to assess the quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (2004 US dollars per QALY) of screening, vaccination of preadolescent girls, and vaccination combined with screening. Screening varied by initiation age (18, 21, or 25 years), interval (every 1, 2, 3, or 5 years), and test (HPV DNA testing of cervical specimens or cytologic evaluation of cervical cells with a Pap test). Testing strategies included: 1) cytology followed by HPV DNA testing for equivocal cytologic results (cytology with HPV test triage); 2) HPV DNA testing followed by cytology for positive HPV DNA results (HPV test with cytology triage); and 3) combined HPV DNA testing and cytology. Strategies were permitted to switch once at age 25, 30, or 35 years.

Results: For unvaccinated women, triennial cytology with HPV test triage, beginning by age 21 years and switching to HPV testing with cytology triage at age 30 years, cost $78,000 per QALY compared with the next best strategy. For girls vaccinated before age 12 years, this same strategy, beginning at age 25 years and switching at age 35 years, cost $41,000 per QALY with screening every 5 years and $188,000 per QALY screening triennially, each compared with the next best strategy. These strategies were more effective and cost-effective than screening women of all ages with cytology alone or cytology with HPV triage annually or biennially.

Conclusions: For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.

Figure 1

Reduction in the lifetime risk of cervical cancer incidence for selected screening strategies. The range (top and bottom edges of the shaded boxes) represents the minimum and maximum reductions achieved for each strategy when a random sample of 50 good-fitting parameter sets was analyzed; the central horizontal line in each box represents the mean reduction achieved. Strategies depicted are as follows: screening alone every 3 or 5 years; vaccination of preadolescent girls alone; and screening every 1, 3, or 5 years combined with vaccination of preadolescent girls. The screening component of the strategies shown uses cytology with human papillomavirus test triage for atypical squamous cells of uncertain significance starting at age 25 years and HPV DNA testing with cytology triage for women older than 35 years.

Figure 2

Potential impact of opportunistic human papillomavirus 16,18 (HPV-16,18) vaccine uptake in women aged 21–29 years and changes in cervical cancer screening behavior. The incremental benefit shown is associated with opportunistic vaccination of women aged 21–24 years (yellow bars) and 25–29 years (red bars), rather than with a targeted program that covers all preadolescent girls aged 9–12 years (green bars), and the influence of their subsequent screening behavior on overall outcomes. For three levels of vaccine coverage (25%, 75%, and 100%), expected incremental changes in quality-adjusted life expectancy associated with less frequent screening, compared with current screening practice, are shown. q3 = triennial screening; vax = HPV vaccination.

Figure 3

Potential impact of human papillomavirus (HPV) DNA testing and HPV-16,18 vaccination on disparities in cervical cancer risk reduction among racial and ethnic groups in the United States. We modeled differential uptake and use of HPV DNA testing and cytology triage in women older than 35 years, of HPV-16,18 vaccination uptake, and of increased adherence to a triennial screening schedule. A) Hypothetical scenario that would worsen disparities. In this scenario, there is preferential uptake (75%) of newer prevention strategies by the lowest-risk subpopulation of white women compared with reduced uptake (25%) in racial and ethnic minority women. B) Hypothetical scenario that would lessen disparities. In this scenario, there is equal level of uptake (50%) in all women, regardless of racial and ethnic group, of newer prevention strategies. In both A and B, gray = the expected reduction in cancer with racial- and ethnicity-specific screening patterns and frequencies by use of cytology alone; blue = the additional incremental benefit conferred by HPV DNA testing and cytology triage in women older than 35 years; orange = the additional incremental benefit conferred by preadolescent HPV vaccination; and green = the additional incremental benefit conferred by increased adherence to a triennial screening schedule.