Fig. 1

Consort diagram of FRIDA nested case-control triage study showing the numbers of women in each step. Triage positive women included HPV16/18 positive (<ASCUS) (n = 508), ASCUS+ (HPV16/18 negative) (n = 277), and HPV16/18 positive and ASCUS+ (n = 78). *Prior to July 2015, 672 out of 863 triage-positive women attended the colposcopy evaluation. Then, 561 women out of 672 who underwent colposcopy had histology results recorded from April 2013 to the time of the study cutoff date on July 15. These 561 women are represented in our sampling frame, from which we selected all the CIN2+ cases (79) and a random selection of three controls per case matched by age (1 CIN1 and 2 NEG). In total, 316 participants were included in our methylation analysis: 79 CIN2+ cases, 79 CIN1, and 158 NEG. The cases included all the CIN2+ detected until July 2015. The three controls per case were randomly selected and matched by age from women with histological diagnoses of CIN1 or less. The remaining 245 triage-positive women with histology results of CIN1 and negative would have been controls but were not selected by the sampling method as we already had adequate power for the study. Abbreviations: hrHPV, high-risk human papillomavirus; HPV16/18, human papillomavirus type 16 or type 18; ASCUS+, atypical squamous cells of undetermined significance or worse; NEG, histologically negative; CIN, cervical intraepithelial neoplasia (of grades 1, 2, and 3)