Detection of human papillomavirus in Papanicolaou smears: correlation with pathologic findings and clinical outcome.

The purpose of this study was to correlate the in situ detection of human papillomavirus (HPV) DNA in archival Papanicolaou (Pap) smears with the pathologic findings and, for atypical squamous cells of undetermined significance (ASCUS), clinical follow-up. Eighty-two Pap smears were destained and analyzed for HPV DNA by in situ hybridization using a consensus probe cocktail that could detect the oncogenic HPV types. "High-risk" HPV DNA was detected in 18 of 23 (78%) low grade SILs, 16 of 40 (40%) ASCUSs, and 1 of 19 (5%) normal Pap smears. The in situ detection of HPV DNA in ASCUS Pap smears with a corresponding biopsy-proven squamous intraepitheal lesion (SIL) within 6 months was significantly greater (14 of 21, 67%) than in smears with corresponding biopsy specimens were negative for SIL (2 of 19, 10%) (p < 0.05). Analysis of the smears negative for HPV using the high-risk probe cocktail with probes for low-risk HPV 6, 11, 42, 43, and 44 increased the percentage of positive smears to 91% (21 of 23) of low grade SILs and 50% (20 of 40) for ASCUS, including 81% (17 of 21) of the women in whom dysplasia developed; there was no change in the percentage of positive cases in normal Pap smears. It is concluded that the in situ detection of HPV DNA in ASCUS cells can help the clinician to differentiate those women at very high risk for a biopsy-proven SIL from those at low risk.