Fig. 4

Benefit of using the S5 classifier as a second triage test for colposcopy referral for a) CIN2+ and b) CIN3+ endpoints. S5 helped reduce unnecessary colposcopy referrals in both the “HPV16/18 neg, ASCUS+” and “HPV16/18 pos, normal cytology” groups. Under the current Mexican algorithm, all HPV16/18 positive and/or ASCUS positive are referred to colposcopy, but we propose to use S5 as second triage test for the discrepant triage groups (“HPV16/18 neg, ASCUS+” and “HPV16/18 pos, normal cytology”) which then decreases the false-positive rate. We therefore defined the following hypothesis to test S5 benefits. In group 1, women were HPV16/18 positive and ASCUS positive and must be referred to colposcopy without any additional triage procedure. In group 2, women were HPV16/18 negative and ASCUS positive and were called for colposcopy, but if we had used S5 methylation as a second triage test, it would have reduced by 50% (CIN2 endpoint) or 43% (CIN3 endpoint) the number of false positives referred to colposcopy. Using S5 methylation as a second triage for women in group 3, who were HPV16/18 positive with normal cytology, would have reduced unnecessary colposcopy referrals by 30% in CIN2+ and 28% in CIN3+. Abbreviations: ASCUS+, atypical squamous cells of undetermined significance or worse; CIN, cervical intraepithelial neoplasia (of grades 1, 2, and 3). The frequency shows the absolute number of women in each group