Development of evidence-based guidelines for follow up of women treated for cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) in Italian screening programmes

Background: The Italian Group for Cervical Cancer Screening (GISCi) promoted the update of recommendations for post Cervical Intraepithelial Neoplasia grade 2 or 3 (CIN2/3) treatment follow up. Methods: A multidisciplinary panel including all the professionals involved in cervical cancer screening and CIN treatment was set up. Systematic reviews have been conducted searching in PubMed. The GRADEpro online tool was used for: defining and prioritizing clinical questions framed in PICOs (Population Intervention Comparator Outcomes); defining and scoring outcomes as critical, important or not important; synthetizing results of the systematic reviews in Evidence to Decision tables and to grade recommendations. Results: A systematic review identified the main prognostic factors, but these have almost no impact in HPV-negative women. Six questions were prioritized for the first phase: 3 about the test (Pap, HPV-DNA or Pap + HPV cotesting or co-testing + colposcopy); 1 about the number of episodes before returning to screening; 2 about the timing of episodes. For the test accuracy direct evidence was available, while for other questions mostly indirect evidence was retrieved in systematic reviews. Conclusions: The panel recommends HPV test or co-testing (conditional either the two), but not Pap test as follow up test (strong). Colposcopy can be added to assess surgical outcomes (conditional either yes or not). Two episodes instead of one, before referring women to regular screening, should be preferred (conditional). The first episode should be 6 months (vs. 12) after treatment (strong), in order to avoid progression of undiagnosed prevalent invasive cancers; the interval between first and second episode may be either 6 or 12 months (conditional).