Ploidy in human papillomavirus positive and negative vulvar squamous cell carcinomas and adjacent skin lesions

To better characterize the two clinicopathologic types of squamous cell carcinoma, human papillomavirus (HPV) positive and negative, and their adjacent skin changes, we performed cytomorphometric analysis on 12 HPV-positive squamous cell carcinomas and adjacent vulvar intraepithelial neoplasia and 22 HPV-negative squamous cell carcinomas and adjacent squamous cell hyperplasia and lichen sclerosis. Our results were that 83% (10 of 12) HPV-positive carcinomas and 78% (7 of 9) adjacent vulvar intraepithelial neoplasia were aneuploid, compared with 59% (13 of 22) HPV-negative carcinomas, 6% (1 of 16) squamous cell hyperplasias and 0% (0 of 20) lichen scleroses. Seventy-five percent (9 of 12) HPV carcinomas and 78% (7 of 9) vulvar intraepithelial neoplasias showed two aneuploid peaks, but no HPV-negative carcinoma or non-neoplastic epithelial lesion showed multiple aneuploid peaks. Fifty percent of squamous cell hyperplasias (8 of 16) and lichen scleroses (10 of 20) adjacent to HPV-negative carcinomas were hypodiploid. The mean DNA indices were: 1.70 for the dominant tumor cell population of HPV-positive carcinoma, 1.64 for the dominant population of vulvar intraepithelial intraepithelial neoplasia, 1.41 for HPV-negative carcinoma, 0.85 for squamous cell hyperplasia and 0.83 for lichen sclerosis. In conclusion, the higher rate of aneuploidy, higher mean DNA index, and presence of multiploid peaks in HPV-positive carcinomas and adjacent vulvar intraepithelial neoplasias compared with the lower rate of aneuploidy, lower mean DNA index, absence of multiploid peaks of HPV-negative carcinomas and tendency to hypodiploidy in squamous cell hyperplasia and lichen sclerosis support the hypothesis that there are two clinicopathologic types of vulvar carcinoma, with different pathogenetic mechanisms. The similarities in ploidy findings between vulvar HPV-positive carcinomas and vulvar intraepithelial neoplasia and those previously published for cervical carcinoma and cervical intraepithelial neoplasia support the view that these two cancers are analogous and have similar pathogenetic mechanisms. The frequent finding of hypodiploidy in squamous cell hyperplasia and lichen sclerosis next to HPV-negative carcinomas requires further investigation of the molecular pathogenesis of this cancer type.