© 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics Although human papillomavirus (HPV) vaccines offer enormous promise for the ultimate control and possible elimination of cervical cancer, barriers to uptake and coverage of the vaccine both in high- and low/middle-income settings mean that advances in secondary prevention continue to be essential to prevent unnecessary deaths and suffering from cervical cancer for decades to come. While cytology (the Pap smear) has reduced cervical cancer incidence and prevalence in jurisdictions where it has been systematically implemented in population-based programs—mainly in high-income settings—limitations inherent to this method, and to program delivery, leave many women still vulnerable to cervical cancer. Recent evidence has confirmed that screening based on HPV testing prevents more invasive cervical cancer and precancerous lesions, and offers innovative options such as self-collection of specimens to improve screening uptake broadly. In this paper, we review key advances, future opportunities, and ongoing challenges for secondary prevention of cervical cancer using HPV-based testing.