Currently, human papillomavirus (HPV) DNA tests validated in large trials and epidemiological studies are the hybrid capture second-generation (HC2) HPV DNA assay and a variety of polymerase chain reaction (PCR) protocols employing degenerate or consensus primers. This article describes the currently available technology for HPV detection and discusses novel technologies and their potential for large-scale screening. Ideally, an HPV test should allow detection of multiple HPV types, identify individual types, and provide quantitative information about the viral load of each individual type found. Moreover, it should be easy to perform, be highly reproducible, with a high specificity and sensitivity, and amenable for high throughput analysis and automation. Because we do not yet fully understand the true value of viral load and the biological relevance of the different HPV types, any HPV test should be able to detect the clinically relevant high-risk types with a sufficient sensitivity of at least 10 000 genome copies per sample. To validate the different current and future test systems and to compare inter-laboratory performance we urgently need reference samples, validated reagents, and standardized protocols.