Human papillomavirus (HPV) is necessary for the development of cervical carcinoma, and incorporation of molecular testing for HPV in screening and patient management has been proposed. Sufficient scientific evidence exists to recommend HPV DNA testing in the triage of women with equivocal cytology and in follow-up after the treatment of precursor lesions. However, due to a low clinical specificity and positive predictive value, HPV DNA testing has so far not been recommended as primary screening in Europe. In general, diagnostic HPV tests have to demonstrate accuracy, reproducibility and clinical utility before they can be used in patient management and implemented in cervical cancer screening programmes. In this article we give an overview of RNA-based HPV diagnostics and the role of E6/E7 mRNA detection as a predictive marker for the development of cervical carcinoma. HPV E6/E7 mRNA testing for high-risk types seems to correlate better with the severity of the lesion compared with HPV DNA testing, and is a potential marker for the identification of women at risk of developing cervical carcinoma. Commercial assays for simultaneous genotyping and detection of E6/E7 mRNA from the five most common high-risk HPV types are now available and require further evaluation for primary screening, triage and follow-up after treatment.