We performed p16(INK4a) immunocytochemical analysis and Hybrid Capture 2 (HC2, Digene, Gaithersburg, MD) high-risk HPV testing on 210 abnormal SurePath (TriPath Imaging, Burlington, NC) Papanicolaou specimens diagnosed as low-grade squamous intraepithelial lesion (LSIL) or-high-grade squamous intraepithelial lesion (HSIL). The results were compared with 121 follow-up biopsy specimens. p16(INK4a) was positive in 57.9% of women-with LSIL compared with 97.1 % of women with HSIL In contrast, HC2 testing was positive in 85. 0% of women with LSIL and 86.4% of women with HSIL. The differences in the positive rates for 16(INK4a) between LSIL and HSIL was significant(P <. 001), whereas,for HC2 it was not (P.264). Inpatients who had cervical biopsies following a cytologic diagnosis of LSIL, the positive predictive value (PPV) of p16(INK4a) for a biopsy of cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3; 33%) was significantly higher than the PPV of HC2 results (21%) (P <.001). Using liquid-based cytology specimens, p16(INK4a) immunocytochemical analysis has a higher PPV than reflex HC2 HPV testing for - identifying CIN2/3 among patients with LSIL and might be useful for selecting patients with LSIL for colposcopy.