Elevated levels of tetraploid cervical cells in human papillomavirus-positive Papanicolaou smears diagnosed as atypical squamous cells of undetermined significance.

Abstract

Recommendations for the proper treatment of women diagnosed with an equivocal atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smear are controversial. To the authors' knowledge, there currently are no methods available that can identify accurately ASCUS/human papillomavirus (HPV)-positive women who have an increased risk of developing progressive cervical lesions without the use of invasive procedures. An additional diagnostic tool is needed to triage women properly who are diagnosed with ASCUS. Numerical chromosomal abnormalities, such as tetraploidy and aneuploidy, frequently accompany cervical carcinoma development and are believed to represent early and important genetic alterations during cervical carcinogenesis. The identification of elevated levels of numerical chromosomal aberrations in women diagnosed with ASCUS Pap smears, therefore, may be of prognostic value. Multiple-probe fluorescence in situ hybridization was used to analyze 1000 cervical epithelial cells from each of 257 women for the presence of numerical chromosomal aberrations. A statistically significant proportion of women diagnosed with HPV-positive ASCUS had elevated levels of tetraploid cervical cells (5 of 69 women) compared with normal/HPV-negative women (0 of 75 women) (P = 0.02). The frequency of numerical chromosomal aberrations in cervical cells obtained from the majority of women diagnosed with an ASCUS Pap smear did not differ significantly from the frequency in women with smears that were diagnosed as normal. However, a modest but statistically significant proportion of women diagnosed as HPV-positive ASCUS did have elevated levels of tetraploid cervical cells, a genetic abnormality often associated with cervical carcinogenesis, suggesting that these women may be at an increased risk of developing more advanced cervical lesions. Given these results, the authors recommend performing additional studies with histologic follow-up.