Human papillomavirus (HPV) vaccination is expected to reduce the burden of cervical cancer in most settings; however, it is also expected to interfere with the effectiveness of screening. In the future, maintaining Pap cytology as the primary cervical screening test may become too costly. As the prevalence of cervical dysplasias decreases, the positive predictive value of the Pap test will also decrease, and, as a result, more women will be referred for unnecessary diagnostic procedures and follow-up. HPV DNA testing has recently emerged as the most likely candidate to replace cytology for primary screening. It is less prone to human error and much more sensitive than the Pap smear in detecting high-grade cervical lesions. Incorporating this test would improve the overall quality of screening programs and allow spacing out screening tests, while maintaining safety and lowering costs. Although HPV testing is less specific than Pap cytology, this issue could be resolved by reserving the latter for the more labour-efficient task of triaging HPV-positive cases. Because most HPV-positive smears would contain relevant abnormalities, Pap cytology would be expected to perform with sufficient accuracy under these circumstances. HPV Pap triage would also provide a low-cost strategy to monitor long-term vaccine efficacy. Although demonstration projects could start implementing HPV testing as a population screening tool, more research is needed to determine the optimal age to initiate screening, the role of HPV typing and other markers of disease progression, and appropriate follow-up algorithms for HPV-positive and Pap-negative women.