Morphometric assessment of the biological potential of human papillomavirus infections in the uterine cervix.

A series of 69 punch biopsies derived from 513 women prospectively followed up for cervical human papillomavirus (HPV) infections (including HPV lesions with and without cervical intraepithelial neoplasia; HPV-CIN, HPV-NCIN), and 42 control cases (consisting of normal epithelia, and classical CIN lesions) were analyzed morphometrically, using a semiautomatic image analyzer (IBS I-KONTRON), to assess the value of morphometric measurements in discriminating between HPV lesions and CIN, and to find out whether these methods are useful in predicting the outcome of cervical HPV infections. Nuclear area and the form factors Ell, Ar, and Pe were calculated on fifty nuclei in each of the three layers of epithelium; deep, intermediate and superficial. The reproducibility of the measurements was calculated for intra- and interobserver variation. HPV typing was completed using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18 and 31. No significant differences were detected by using the form factors (Ell, Ar, Pe), when HPV lesions were compared with the normal epithelium, or with classical CIN lesions, in any of the epithelial layers. The nuclear area was significantly larger in all the epithelial layers in HPV-CIN I, and HPV-CIN II lesions as compared with CIN I and CIN II cases (p less than 0.001), p less than 0.001, p less than 0.005 and p less than 0.001, for deep, intermediate and superficial layers between HPV-CIN I/CIN I, and for all layers in HPV-CIN II/CIN II comparisons, respectively). This was also true when the values of nuclear area in HPV-NCIN I, HPV-CIN II and HPV-CIN III lesions were compared with the normal epithelium (p less than 0.001 for all layers). In the most severe lesions, no significant differences existed between HPV-CIN III and CIN III cases. Nuclear area measurement could not predict, however, the HPV type found in the lesion, or their natural history established by prospective follow-up.