Study population
Participants were women who visited gynecology clinics in four hospitals for routine cervical cancer or precancer screening between December 2017 and November 2018, aged from 27 to 70 years. The protocol, inclusion and exclusion criteria of the study are shown in Figure 1 .
At the first visiting for gynecological examination in multi-center clinics, cervical samples were obtained to conduct the HPV detection, cytology and S5 methylation analyses. Women with HPV-positive results and/or abnormal cytology results (HPV positive and/or cytology with ASCUS, LSIL, ASC-H, HSIL or CC) at the first visiting time were recruited in the study. All the included participants were divided into two groups, women with HPV16/18+ and/or ≥ (TCT)HSIL result of cytology at first visiting time were divided into receive immediate colposcopy group (IC group; n=602), women with (“HPV positive except HPV16/18” and “abnormal cytology results except ≥ (TCT)HSIL”) were divided into repeat follow-up group (RF group; n=1644) including scheduled cytology and HPV tests every 6 months for 2 years follow-up period (which means scheduled study visit at 6, 12, 18 and 24 months). Colposcopy and biopsies were performed if women were divided into the IC group, also colposcopy and biopsies were performed if either repeated ≥LSIL or repeated hrHPV+ was observed during the 24-month follow-up period in the RF group. All the histological samples and cytology samples were reviewd by a standardized group of pathologists, all the pathologists and cytopathologists were blinded to the HPV infection status.