Exposure Definition in Case-Control Studies of Cervical Cancer Screening: A Systematic Literature Review

Cancer Epidemiol Biomarkers Prev. 2021 Dec;30(12):2154-2166. doi: 10.1158/1055-9965.EPI-21-0376. Epub 2021 Sep 14.


The first step in evaluating the effectiveness of cervical screening is defining exposure to screening. Our aim was to describe the spectrum of screening exposure definitions used in studies of the effectiveness of cervical screening. This systematic review included case-control studies in a population-based screening setting. Outcome was incidence of cervical cancer. Three electronic databases were searched from January 1, 2012 to December 6, 2018. Articles prior to 2012 were identified from a previous review. The qualitative synthesis focused on describing screening exposure definitions reported in the literature and the methodologic differences that could have an impact on the association between screening and cervical cancer. Forty-one case-control studies were included. Six screening exposure definitions were identified. Cervical cancer risk on average decreased by 66% when screening exposure was defined as ever tested, by 77% by time since last negative test, and by 79% after two or more previous tests. Methodologic differences included composition of the reference group and whether diagnostic and/or symptomatic tests were excluded from the analysis. Consensus guidelines to standardize exposure definitions are needed to ensure evaluations of cervical cancer screening can accurately measure the impact of transitioning from cytology to human papillomavirus-based screening and to allow comparisons between programs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Mass Screening / statistics & numerical data*
  • Papillomavirus Infections / diagnosis
  • Uterine Cervical Neoplasms / prevention & control*