Significant changes in cervical cancer screening practice, guidelines, and prevention of cervical cancer have taken place in recent years including the raising of initial cervical cancer screening age, changes in frequency of cytology screening, and the adoption of high risk HPV and cytology co-testing for some patients; the introduction of the bivalent, quadrivalent, and 9-valent HPV vaccines; and the recent approval of high risk HPV testing as primary screening with the use of cytology as triage in positive cases. This review discusses the significance of primary HPV screening, the impact of HPV vaccination in the prevalence of cervical cancer and its precursors, the interplay between high risk HPV testing and vaccination, and the implications for clinical and cytological management. Future strategies for cervical screening in the post-vaccination era are also discussed.