Screening for Cervical Cancer in Primary Care: A Decision Analysis for the US Preventive Services Task Force

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1.

Model Schematic. The main health states of the natural history model comprise no infection, HPV infection (by genotype), precancer (cervical intraepithelial neoplasia or CIN, grades 2 and 3), invasive cancer (by stage), hysterectomy, and death (from all-causes or from cervical cancer). Movement between these health states occur as monthly transitions. The model focuses on squamous cell carcinoma, the most common histologic subtype of cervical cancer. Screening is used to detect the presence of CIN 2 or 3, which can be treated and removed before progressing to cancer, as well as for early detection of invasive cancer.

Figure 2.

Efficiency Frontiers. These graphs show results from the efficiency analysis in terms of colposcopies per life-year gained (colpo/LYG) (panel A), tests per life-year gained (tests/LYG) (panel B), and colposcopies per cervical cancer case averted (colpos/(CC avt) (panel C) for all 19 cervical cancer screening strategies. Strategies varied in terms of primary screening test (shape: diamond=cytology with a switch to cotesting; circle=cytology with a switch to primary HPV testing with HPV-16/18 genotype testing for triage of HPV-positive women; square=cytology with a switch to primary HPV testing with cytology triage of HPV-positive women; triangle=cytology only); screening interval (shape border: grey=3-year; black=5-year); switch age from cytology to primary HPV testing or cotesting (pattern: x=25 years; checker=27 years; diagonal=30 years). The efficiency ratios were calculated as the additional number of harms (i.e., colposcopies or tests) divided by the additional benefits (i.e., LYG or CC averted) of a specific strategy compared to the strategy with the next fewer harms. Efficient strategies (i.e., that lie on the efficiency frontier) 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; all other strategies (i.e., that do not lie on the efficiency frontier) were considered “inefficient.” All strategies assume cytology alone starting at age 21 years and screening end age of 65 years. Tests include the total number of screening tests over the lifetime of screening, including both routine screening and any surveillance testing but not diagnostic (i.e., colposcopy/biopsy) testing.

Figure 2.

Efficiency Frontiers. These graphs show results from the efficiency analysis in terms of colposcopies per life-year gained (colpo/LYG) (panel A), tests per life-year gained (tests/LYG) (panel B), and colposcopies per cervical cancer case averted (colpos/(CC avt) (panel C) for all 19 cervical cancer screening strategies. Strategies varied in terms of primary screening test (shape: diamond=cytology with a switch to cotesting; circle=cytology with a switch to primary HPV testing with HPV-16/18 genotype testing for triage of HPV-positive women; square=cytology with a switch to primary HPV testing with cytology triage of HPV-positive women; triangle=cytology only); screening interval (shape border: grey=3-year; black=5-year); switch age from cytology to primary HPV testing or cotesting (pattern: x=25 years; checker=27 years; diagonal=30 years). The efficiency ratios were calculated as the additional number of harms (i.e., colposcopies or tests) divided by the additional benefits (i.e., LYG or CC averted) of a specific strategy compared to the strategy with the next fewer harms. Efficient strategies (i.e., that lie on the efficiency frontier) 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; all other strategies (i.e., that do not lie on the efficiency frontier) were considered “inefficient.” All strategies assume cytology alone starting at age 21 years and screening end age of 65 years. Tests include the total number of screening tests over the lifetime of screening, including both routine screening and any surveillance testing but not diagnostic (i.e., colposcopy/biopsy) testing.

Figure 2.

Efficiency Frontiers. These graphs show results from the efficiency analysis in terms of colposcopies per life-year gained (colpo/LYG) (panel A), tests per life-year gained (tests/LYG) (panel B), and colposcopies per cervical cancer case averted (colpos/(CC avt) (panel C) for all 19 cervical cancer screening strategies. Strategies varied in terms of primary screening test (shape: diamond=cytology with a switch to cotesting; circle=cytology with a switch to primary HPV testing with HPV-16/18 genotype testing for triage of HPV-positive women; square=cytology with a switch to primary HPV testing with cytology triage of HPV-positive women; triangle=cytology only); screening interval (shape border: grey=3-year; black=5-year); switch age from cytology to primary HPV testing or cotesting (pattern: x=25 years; checker=27 years; diagonal=30 years). The efficiency ratios were calculated as the additional number of harms (i.e., colposcopies or tests) divided by the additional benefits (i.e., LYG or CC averted) of a specific strategy compared to the strategy with the next fewer harms. Efficient strategies (i.e., that lie on the efficiency frontier) 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; all other strategies (i.e., that do not lie on the efficiency frontier) were considered “inefficient.” All strategies assume cytology alone starting at age 21 years and screening end age of 65 years. Tests include the total number of screening tests over the lifetime of screening, including both routine screening and any surveillance testing but not diagnostic (i.e., colposcopy/biopsy) testing.