Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus

Abstract

Background: Current US cervical cancer screening guidelines do not differentiate recommendations based on a woman's human papillomavirus (HPV) vaccination status. Changes to cervical cancer screening policies in HPV-vaccinated women should be evaluated.

Methods: We utilized an individual-based mathematical model of HPV and cervical cancer in US women to project the health benefits, costs, and harms associated with screening strategies in women vaccinated with the bivalent, quadrivalent, or nonavalent vaccine. Strategies varied by the primary screening test, including cytology, HPV, and combined cytology and HPV "cotesting"; age of screening initiation and/or switching to a new test; and interval between routine screens. Cost-effectiveness analysis was conducted from the societal perspective to identify screening strategies that would be considered good value for money according to thresholds of $50 000 to $200 000 per quality-adjusted life-year (QALY) gained.

Results: Among women fully vaccinated with the bivalent or quadrivalent vaccine, optimal screening strategies involved either cytology or HPV testing alone every five years starting at age 25 or 30 years, with cost-effectiveness ratios ranging from $34 680 to $138 560 per QALY gained. Screening earlier or more frequently was either not cost-effective or associated with exceedingly high cost-effectiveness ratios. In women vaccinated with the nonavalent vaccine, only primary HPV testing was efficient, involving decreased frequency (ie, every 10 years) starting at either age 35 years ($40 210 per QALY) or age 30 years ($127 010 per QALY); with lower nonavalent vaccine efficacy, 10-year HPV testing starting at earlier ages of 25 or 30 years was optimal. Importantly, current US guidelines for screening were inefficient in HPV-vaccinated women.

Conclusions: This model-based analysis suggests screening can be modified to start at later ages, occur at decreased frequency, and involve primary HPV testing in HPV-vaccinated women, providing more health benefit at lower harms and costs than current screening guidelines.

Figure 1.

Health benefits and costs of cervical cancer screening strategies in women vaccinated with the bivalent or quadrivalent vaccine (human papillomavirus [HPV]–2, HPV-4). The figure displays the trade-off of quality-adjusted life-years (QALYs; left y-axis) and reductions in lifetime cervical cancer risk (right y-axis) against lifetime costs (x-axis) for each of the screening strategies. The white circle represents no screening (ie, vaccination only). The colors represent screening test: Green indicates cytology testing (“Cyto”); red indicates primary HPV testing (“HPV”); blue indicates cytology and HPV cotesting (“Cotest”). The color shades represent the age of screening initiation: Darkest indicates age 21 years (with or without a switch to another primary test); next darkest indicates age 25 years; lighter indicates age 30 years; lightest indicates age 35 years. The shapes represent screening interval: Circle indicates three-year screening; triangle represents four-year screening; square represents five-year screening. For all scenarios, routine screening ends at age 65 years. The curve indicates the strategies that are efficient; the incremental cost-effectiveness ratios of strategies on the curve represent the increase in mean lifetime cost divided by the increase in mean QALYs compared with the next less costly strategy, across 50 top-fitting parameter sets. Both QALYs and lifetime costs are discounted at 3% per year. HPV = human papillomavirus; QALY = quality-adjusted life-year.

Figure 2.

Health benefits and costs of cervical cancer screening strategies in women vaccinated with the nonavalent vaccine (human papillomavirus [HPV]-9). The figure displays the trade-off of quality-adjusted life-years (QALYs; left y-axis) and reductions in lifetime cervical cancer risk (right y-axis) against lifetime costs (x-axis) for each of the screening strategies. The white circle represents no screening (ie, vaccination only). The colors represent screening test: Green indicates cytology testing (“Cyto”); red indicates primary HPV testing (“HPV”); blue indicates cytology and HPV cotesting (“Cotest”). The color shades represent the age of screening initiation: Darkest indicates age 21 years (with or without a switch to another primary test); next darkest indicates age 25 years; medium indicates age 30 years; lighter indicates age 35 years; lightest indicates age 40 years. The shapes represent screening interval: Circle indicates three-year screening; triangle represents four-year screening; square represents five-year screening; asterisk represents 10-year screening; long dash represents three-time screening over the lifetime; short dash represents two-time screening over the lifetime; cross indicates one-time screening over the lifetime. For all scenarios, routine screening ends at age 65 years. The curve indicates the strategies that are efficient; the incremental cost-effectiveness ratios of strategies on the curve represent the increase in mean lifetime cost divided by the increase in mean QALYs compared with the next less costly strategy, across 50 top-fitting parameter sets. Both QALYs and lifetime costs are discounted at 3% per year. HPV = human papillomavirus; QALY = quality-adjusted life-year.

Figure 3.

Harms vs benefits of efficient strategies. The figure displays the trade-off of colposcopy referral rates (left y-axis) and reductions in lifetime cervical cancer risk (right y-axis) for screening strategies that were efficient (ie, on the efficiency frontier) in women vaccinated with the bivalent or quadrivalent vaccine (top) or the nonavalent vaccine (bottom). Bars represent the number of colposcopy referrals per 1000 women over the lifetime, starting at age 21 years: Green bars indicate strategies that are considered cost-effective according to benchmarks of good value for money in the United States (25); gray bars indicate current US guidelines-based strategies (1,2); and blue bars indicate the remaining efficient strategies. The red diamonds represent the reductions in lifetime cervical cancer risk associated with each strategy compared with no intervention.