High-risk human papillomavirus (hrHPV) bearing cervical intraepithelial neoplasia (CIN) is considered, as the real precursor lesion of cervical cancer and persistence of an hrHPV infection is necessary for the progression to cervical cancer. This knowledge warrants the use of hrHPV testing as an adjunct to cervical cytology in population-based screening programmes and for monitoring therapy efficacy of high-grade CIN lesions. Replacement of cytology by hrHPV testing altogether is considered, but for this to be (cost-) effective, accurate information about the specificity of the hrHPV test is required. Additional test systems that can be used to stratify women with a positive hrHPV test are HPV genotyping, viral load analysis and hrHPV mRNA analysis. The need for HPV genotyping of cervical smears is illustrated by the increased risk for high-grade cervical lesions associated with HPV types 16 and 18. In particular, for women who have normal but persistently (>1 year) HPV18-positive smears, endocervical curettage is suggested (evidently considering the age and possible future pregnancies of the respective woman) because HPV18 is associated with glandular lesions in the cervix, which are difficult to detect by cytology.