In order to investigate the reliability of detection of human papillomavirus (HPV) DNA in cervical smears, we have compared the performance of two HPV PCR systems, the CPI/IIG and MY09/11 primer-mediated PCRs and the Hybrid Capture System HPV DNA detection test (hybrid capture assay), in detecting HPV DNA in cervical smears. We also included in our study the MY09/11B PCR plus SHARP (solution hybridization assay for PCR products) Signal System. This SHARP Signal System was recently developed to detect MY09/11B-generated biotinylated PCR products. The detection rate of the hybrid capture assay was lower than those of the CPI/IIG and MY09/11 PCRs and the MY09/11B PCR plus SHARP Signal System. The detection rates of the CPI/IIG PCR and the MY09/11B PCR plus SHARP Signal System were similar and higher than that of the conventional MY09/11 PCR system. The agreement beyond chance of the PCR methods was nearly perfect (kappa value between 0.82 and 0.84). The agreement beyond chance of the hybrid capture assay and the PCR methods was fair to good (kappa value between 0.64 and 0.70). The systems detected HPV DNA in different but overlapping sets of smears. Our results indicate that each of the detection methods alone underestimates the prevalence of HPV.