Aberrant, highly hyperdiploid cells in human papillomavirus-positive, abnormal cytologic samples are associated with progressive lesions of the uterine cervix

BACKGROUND: Infection with oncogenic-type human papillomavirus (HPV) and consecutive cytologic abnormalities of the uterine cervix precede the evolution of carcinoma. However, the specificity of both changes is too low to predict the true malignant potential of the change in a given time point, because the majority of the HPV infections revert to normal with time. In preliminary studies, the authors demonstrated that, among many dysregulatory phenomena at the cytologic level, the occurrence of significant DNA content aberrations were in good correlation with progressive cervical changes; and, as a marker for this, the significance of cells with nuclear DNA content > 9c (9c cells) was investigated using slide-based cytometry. The objective of the current study was to determine whether 9c cells in cytologic samples that presented with dysplasia and with high-risk HPV types were associated with the development of higher grade cervical intraepithelial neoplasia (CIN II+). METHODS: Samples with positive cytologic diagnoses (atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion [LSIL], and high-grade squamous intraepithelial lesion [HSIL]) were evaluated for both parameters and were related to outcomes and, if available, to histology results over a follow-up of up to 4 years. RESULTS: Although the presence of high-risk HPV was demonstrable in almost all samples with CIN II+ (96.7%), the virus genome alone proved to have a poor positive predictive value (56.1%) for higher grade CIN. Cytology and the demonstration of 9c cells resulted in less sensitivity compared with the occurrence of high-risk HPV (70.4% and 73.7%, respectively) but in significantly greater specificity (91.3% and 89.2%, respectively). Moreover, a positive predictive value of 81.8% for CIN II+ could be calculated for 9c cells. HSIL morphology, unfavorable HPV type, and DNA cytometry together excluded the highest rate of CIN > or = II with 100% sensitivity and 91.3% specificity. CONCLUSIONS: Biologic parameters, in addition to cytology, help to define the nature of cervical dysplasias more accurately. Oncogenic HPV types and hyperdiploid cells with DNA content > 9c disclosed cytologic changes with the greatest malignant potential. Cancer