Polymerase chain reaction to detect high-risk human papillomavirus has been suggested as a gold standard for cytology. The Netherlands and Surinam were prospectively compared in regard to the proportions of Negative, Atypical Squamous Cells of Undetermined Significance, and Squamous Intraepithelial Lesion smears that had detectable high-risk human papillomavirus. For the Netherlands, 14 600 negative, 270 Atypical Squamous Cells of Undetermined Significance and 120 Squamous Intraepithelial Lesion smears were evaluated by polymerase chain reaction. For Surinam, 150 negative, 50 Atypical Squamous Cells of Undetermined Significance, and 150 Squamous Intraepithelial Lesion smears were evaluated by polymerase chain reaction. In all, 4% of Dutch and 80% of Surinamese negative smears had detectable high-risk human papillomavirus (chi2=1313, P<0.00001). In total, 41.9% of Dutch and 84% of Surinamese Atypical Squamous Cells of Undetermined Significance smears had detectable high-risk human papillomavirus (chi2=28, P<0.00001). Totally, 67.5% of Dutch and 94% of Surinamese SIL smears had detectable high-risk human papillomavirus (chi2=30, P<0.00001). The Negative: Atypical Squamous Cells of Undetermined Significance odds ratio was 0.058 for the Netherlands and 0.762 for Surinam (chi2homog=31, P<0.00001). The Negative: Squamous Intraepithelial Lesion odds ratio was 0.020 for the Netherlands and 0.255 for Surinam (chi2homog=31, P<0.00001). The Atypical Squamous Cells of Undetermined Significance: Squamous Intraepithelial Lesion odds ratio was 0.347 for the Netherlands and 0.335 for Surinam (chi2homog=0.005, P>0.75). Human papillomavirus DNA testing may not be a suitable gold standard in general because its use would make specificity and sensitivity prevalence-dependent. A new statistic, the percent of Negative pap smears with detectable high-risk human papillomavirus, is posited, which may be important if human papillomavirus DNA testing is used clinically.