The validity of human papillomavirus (HPV) detection using the hybrid capture assay (HCA) was compared with the polymerase chain reaction (PCR) in 38 patients with high-grade squamous intraepithelial lesions (HSILs). HCA and PCR showed 84% agreement for HPV detection. HCA missed a significant higher proportion of HSIL compared with PCR (21% vs. 5%; P = .04). Thus, the sensitivity of HCA should be increased before this test can be recommended for HSIL.