Importance: Evidence on the relative benefits and harms of primary high-risk human papillomavirus (hrHPV) testing is needed to inform guidelines.
Objective: To inform the US Preventive Services Task Force by modeling the benefits and harms of various cervical cancer screening strategies.
Design, Setting, and Participants: Microsimulation model of a hypothetical cohort of women initiating screening at age 21 years.
Exposures: Screening with cytology, hrHPV testing, and cytology and hrHPV cotesting, varying age to switch from cytology to hrHPV testing or cotesting (25, 27, 30 years), rescreening interval (3, 5 years), and triage options for hrHPV-positive results (16/18 genotype, cytology testing). Current guidelines-based screening strategies comprised cytology alone every 3 years starting at age 21 years, with or without a switch to cytology and hrHPV cotesting every 5 years from ages 30 to 65 years. Complete adherence for all 19 strategies was assumed.
Main Outcomes and Measures: Lifetime number of tests, colposcopies, disease detection, false-positive results, cancer cases and deaths, life-years, and efficiency ratios expressing the trade-off of harms (ie, colposcopies, tests) vs benefits (life-years gained, cancer cases averted). Efficient strategies were those that yielded more benefit and less harm than another strategy or a lower harm to benefit ratio than a strategy with less harms.
Results: Compared with no screening, all modeled cervical cancer screening strategies were estimated to result in substantial reductions in cancer cases and deaths and gains in life-years. The effectiveness of screening across the different strategies was estimated to be similar, with primary hrHPV-based and alternative cotesting strategies having slightly higher effectiveness and greater harms than current guidelines-based cytology testing. For example, cervical cancer deaths associated with the guidelines-based strategies ranged from 0.30 to 0.76 deaths per 1000 women, whereas new strategies involving primary hrHPV testing or cotesting were associated with fewer cervical cancer deaths, ranging from 0.23 to 0.29 deaths per 1000 women. In all analyses, primary hrHPV testing strategies occurring at 5-year intervals were efficient. For example, 5-year primary hrHPV testing (cytology triage) based on switching from cytology to hrHPV screening at ages 30 years, 27 years, and 25 years had ratios per life-year gained of 73, 143, and 195 colposcopies, respectively. In contrast, strategies involving 3-year hrHPV testing had much higher ratios, ranging from 2188 to 3822 colposcopies per life-year gained. In most analyses, strategies involving cotesting were not efficient.
Conclusions and Relevance: In this microsimulation modeling study, it was estimated that primary hrHPV screening may represent a reasonable balance of harms and benefits when performed every 5 years. Switching from cytology to hrHPV testing at age 30 years yielded the most efficient harm to benefit ratio when using colposcopy as a proxy for harms.