A critical evaluation of three methods of studying cell proliferation in human cervical epithelium

Three experiments describing applications of cell kinetic techniques to the human cervix are presented. The mitotic index is shown not to be associated with histologic differentiation, node metastasis, or survival rates in cervical squamous carcinoma, although inherent sources of inaccuracy may be a contributory factor. The second experiment, a new application of the metaphase arrest technique to cervical epithelium, allows an estimation of cell production rates in normal, dysplastic, wart-affected cervical epithelium, and in invasive carcinoma. Confidence limits are wide, rendering individual values imprecise in isolation. The third project describes a modification of in vitro labeling of cervical biopsy specimens using tritiated thymidine followed by autoradiography. Labeling indexes are produced for normal and pathological cervical epithelium. Although successful labeling was not achieved in every case, the labeling index for cervical intraepithelial neoplasia (CIN stage III) is significantly greater than for normal epithelium. The metaphase arrest technique appears to be the most applicable of the three to the study of the human cervix, yielding a useful parameter of cell proliferative activity. The labeling index gives an indication of activity that is useful for comparative studies, but that does not provide data regarding actual proliferative rates. More sophisticated experiments using radioactive materials are ethically inadmissable.