Human papillomavirus (HPV) screening is effective in preventing invasive cervical cancers, but because most HPV positive women have transient infections that will regress naturally, many colposcopy referrals and associated cervical excisional treatments are unnecessary and could be reduced with better triage tests. A WIPH-led study on a population-based sample of high risk HPV positive women with cervical biopsies within 12 months after routine cervical screening has shown that DNA methylation using the S5 classifier as a triage test has significantly greater sensitivity, and similar positive predictive value for detection of cervical intrathelial neoplasia grade 3 or greater (CIN3+) compared with HPV genotyping or cytology triage. S5 is also able to improve discrimination between low- (<CIN2) and high-grade (CIN2/CIN3+) cervical pre-cancer, a finding of importance for management of CIN2, given the complexity and uncertainty associated with this diagnosis. Co-author Belinda Nedjai said: “The use of DNA methylation marker for triage of high risk HPV positive women could potentially reduce the number of women referred to colposcopy by 10 to 15%”.