Torres-Poveda K, et al. - Researchers conducted this cross-sectional study to determine the population-based prevalence of high-risk Human Papillomavirus (HR-HPV) infection and related cofactors in female beneficiaries of the Institute of Security and Social Services for State Workers (ISSSTE) attending the Program for HPV Screening and Early Detection of Cervical Cancer and registered in the Women’s Cancer Detection System (SIDECAM). Cervical samples were analyzed for HR-HPV from 115,651 female users of the HPV screening program and early detection of cervical cancer recruited at 23 ISSSTE care centers. In the 2013–2015 period, the overall prevalence of HR-HPV infection among female ISSSTE beneficiaries was 13%. The prevalence of HR-HPV in female users of the Program for HPV Screening and Early Detection of Cervical Cancer of the ISSSTE is comparable to the population-based prevalence previously reported in Mexican women without cervical alterations. Age, number of sexual partners, history of hormonal contraception, and smoking habit have been found to be positively linked to HR-HPV infection; and number of sexual partners and smoking with HPV-16 infection and infection by non-16/18 HR-HPV. In cytology studies and HPV testing, the ISSSTE has a robust early detection program that allows us to know the prevalence of HR-HPV infection in the female user population.