Given the strong etiologic link between high‐risk HPV infection and cervical cancer high‐risk HPV testing is now being considered as an alternative for cytology‐based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high‐risk HPV is not inherently useful unless it is informative for the presence of high‐grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high‐risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high‐grade CIN and cervical cancer to minimize redundant or excessive follow‐up procedures for high‐risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high‐risk HPV testing by hybrid capture 2 and GP5+/6+‐PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high‐risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high‐risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. © 2008 Wiley‐Liss, Inc.