Human papillomavirus (HPV) testing has clearly demonstrated a higher sensitivity but somewhat lower specificity than cytology. However, there are still issues regarding how best to use it in primary screening. In countries where cytology is of good quality, the most interesting possibility for primary screening is to use HPV testing as the sole screening modality with cytology reserved for triage of HPV-positive women. In countries with a less established infrastructure, however, use of HPV alone would also be attractive, although rapid, simple tests followed by immediate treatment are needed to minimize the number of visits and make best use of limited resources. Several approaches to deal with the lower specificity of HPV testing are also examined. These include HPV typing with a different management strategy for HPV-16 and -18/45, use of viral load to exclude infections unlikely to be associated with > or =CIN-2, and markers of proliferative lesions such as p16 and mRNA or cell-cycle markers such as cdc6 or the mcm5 proteins. Micro-array studies offer the prospect of discovering new, better DNA- or RNA-based diagnostics. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships and these issues are also discussed. Ongoing HPV studies are identified and briefly reviewed.