Polymerase chain reaction-assisted evaluation of low and high grade squamous intraepithelial lesion cytology and reappraisal of the Bethesda System.

Between January 1991 and 1992, 5,652 cervical smears from 4,918 women were classified according to the traditional Papanicolaou/cervical intraepithelial neoplasia (CIN) categories and to the recently developed Bethesda System. Koilocytosis without atypia was identified in 3.7% (183 cases), CIN 1 in 1.8% (87 cases) and high grade squamous intraepithelial lesions (SILs) (CIN 2 and 3) in 1.9% (93 cases) (total, 363/4,918 = 7.4%). Human papillomavirus (HPV)-directed polymerase chain reaction analysis with general primers and subsequent hybridization with HPV 16/18 probe cocktail was carried out in 35% of cases with koilocytosis and dysplasia of any degree (127/363 cases). Seventy-five percent (95 cases) were positive in contrast to a detection rate of 30.8% (53/172 cases) for nonsuspicious smears. While low grade SILs were HPV positive in 67% (koilocytosis only) and 75% (CIN 1), high grade SILs harbored HPV in 87%. The rate of HPV 16/18 infections varied from 71.9% in low grade SILs to 88.9% in high grade SILs. Our results point to the questionable value of koilocytosis as a specific marker of HPV infection and call for confirmatory tests prior to classifying cervical smears suggestive of HPV infection in the low grade SIL category.