in progress

Draft Research Plan

Cervical Cancer: Screening

October 28, 2021

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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Figure 1 is the analytic framework that depicts the three Key Questions (KQs) to be addressed in the systematic review. The figure addresses the comparative effectiveness of different screening strategies on precancer detection, cancer incidence, or morbidity/mortality (KQ1), as well as the test accuracy of and adherence to self-collection hrHPV vaginal samples (KQ2). Additionally, the comparative harms of the different cervical cancer screening strategies is displayed (KQ3).

  1. What is the comparative effectiveness of different cervical cancer screening strategies (i.e., test, mode of collection, and interval of testing) on precancer detection, cancer incidence, morbidity, or mortality?
    1. Does the comparative effectiveness vary by population (e.g., by age, gender, race and ethnicity, or human papillomavirus [HPV] immunization status)?
  2. What is the test accuracy of and adherence to self-collected high-risk HPV vaginal samples?
    1. Does the test accuracy or adherence vary by population (e.g., by age, gender, race and ethnicity, or HPV immunization status)?
  3. What are the comparative harms of different cervical cancer screening strategies (i.e., test, mode of collection, and interval of testing)?
    1. Do the comparative harms vary by population (e.g., by age, gender, race and ethnicity, or HPV immunization status)?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the comparative test accuracy of high-risk HPV tests used in U.S.-based clinical practice?
  2. How do different levels of racism and other factors contribute to inequities in cervical cancer incidence and health outcomes? (For example, the increased incidence and mortality from cervical cancer among Black and Latinx populations.)
  3. Are there effective interventions that could redress existing inequities in morbidity and mortality from cervical cancer, such as strategies to improve screening rates and followup to abnormal screening results?

The proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions.

  Included Excluded
Aim Studies targeting cervical cancer screening Use of HPV or cytology testing for posttreatment surveillance or other purposes
Populations Persons who have a cervix
  • High-risk populations (e.g., persons with HIV, in utero exposure to diethylstrilbestrol, or previous treatment for cervical cancer or a high-grade precancerous lesion)
  • Pregnant persons
Interventions KQs 1, 3:
  • Test: Any currently available hrHPV assay*:
    • Alone
    • In combination with cytology triage of positive hrHPV (reflex cytology)
    • In combination with cytology (cotesting)
  • Mode of collection: Self- or clinician-collected hrHPV samples
  • Intervals of testing: Any interval of screening

KQ 2:

  • Self-collected hrHPV sample
 Non-hrHPV screening strategies
Comparators KQs 1, 3: Any alternate test, assay or both; mode of collection or interval of testing

KQ 2:

  • Clinician-collected hrHPV sample
  • Reference standard
 No screening
Outcomes KQ 1:
  • Precancerous lesions (i.e., CIN2+, CIN3+)
  • Invasive cervical cancer
  • Mortality (all-cause or cervical cancer)
  • Quality of life or other cancer-related morbidity

KQ 2:

  • Test accuracy (e.g., sensitivity, specificity, false-positive and false-negative test results)
  • Adherence to screening

KQ 3:

  • Rates of false-positive and false-negative screening test results
  • Rates of colposcopy, biopsy, or both and related procedural harms
  • Psychological harms (e.g., stigma, labeling, partner discord, depression/anxiety)
  
Study Designs KQs 1, 3:
  • Individual patient data meta-analyses and systematic reviews
  • Randomized, controlled trials; controlled clinical trials
  • Cohort studies with contemporaneous controls
  • Population-based nested case-control studies

KQ 2:

  • Diagnostic test accuracy studies
  • Participation trials (for adherence only)
 KQs 1, 3:
  • Non-nested case-control studies
  • Case reports
  • Case series
  • Narrative reviews
  • Editorials

KQ 2:

  • Diagnostic test accuracy studies without a reference standard
Setting Primary care (e.g., internal medicine, family medicine, obstetrics/gynecology) other settings generalizable to primary care (e.g., university-based health clinics, mobile clinics, sexually transmitted infection clinics, family planning clinics), or any setting for self-collection of samples

 
Country Countries with cervical cancer screening programs comparable to those of the United States and categorized as “Very High” or equivalent on the 2014 Human Development Index (as defined by the  United Nations Development Programme) Countries not categorized as “Very High” on the Human Development Index or not applicable to U.S. clinical settings or populations
Language English only Non-English publications
Quality Fair- or good-quality, according to USPSTF design-specific criteria Poor-quality, according to USPSTF design-specific criteria

* HPV tests approved by the U.S. Food and Drug Administration include: the Hybrid Capture 2 High-Risk HPV DNA Test (Qiagen, Hilden, Germany); cobas HPV Test (Roche Molecular Systems, Inc., Pleasanton, CA); APTIMA® HPV and HPV 16, 18/45 Assays (Hologic, Inc., Madison, WI); Cervista™ HPV 16/18 and Cervista™ HR HPV (Hologic, Inc., Madison, WI); and Onclarity HPV™ (Becton Dickinson, Franklin Lakes, NJ).

The USPSTF intends to commission a decision model to accompany this evidence review.