From a clinical point of view, testing for a broad spectrum of high-risk human papillomavirus (hrHPV) is only useful when a positive hrHPV test result is informative about the presence of high-grade cervical intraepithelial neoplasia or cervical cancer (CIN 2 or worse). Two hrHPV tests, i.e. HC2 and GP5+/6+, have shown in large clinical trials that they perform better in the detection of CIN 2+/CIN 3+ lesions than cytology and thus have been clinically validated. Consequently these tests are now considered as alternative screening tools for cytology in cervical screening. Candidate hrHPV tests to be used for cervical screening should have a similar balance between sensitivity and specificity for CIN 2+ lesions as these two clinically validated hrHPV tests in order to prevent redundant or excessive follow-up procedures for women with transient hrHPV infections or hrHPV-positive women without cervical lesions. The data from these large prospective clinical studies can be used to set standards for the clinical performance and characteristics of the candidate hrHPV test. To prevent costly validation trajects of candidate hrHPV tests and based on the available data from large clinical studies we demonstrate how guidelines for hrHPV test requirements and guidelines for clinical validation of candidate hrHPV tests have been developed, and how these guidelines should be used in cervical screening. It is expected that the use of these guidelines will facilitate implementation of hrHPV testing in primary cervical screening.