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 car cinoma, human papillomavirus (HPV) positive and negative, and their adjacen t skin changes, we performed cytomorphometric analysis on 12 HPV-positive s quamous cell carcinomas and adjacent vulvar intraepithelial neoplasia and 2 2 HPV-negative squamous cell carcinomas and adjacent squamous cell hyperpla sia 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-f ive percent (9 of 12) HPV carcinomas and 78% (7 of 9) vulvar intraepithelia l neoplasias showed two aneuploid peaks, but no HPV-negative carcinoma or n onneoplastic epithelial lesion showed multiple aneuploid peaks. Fifty perce nt 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 intraepithelia l neoplasia, 1.41 for HPV-negative carcinoma, 0.85 for squamous cell hyperp lasia and 0.83 for lichen sclerosis. In conclusion, the higher rate of aneu ploidy, higher mean DNA index, and presence of multiploid peaks in HPV-posi tive carcinomas and adjacent vulvar intraepithelial neoplasias compared wit h 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 pathogenet ic mechanisms. The similarities in ploidy findings between vulvar HPV-posit ive carcinomas and vulvar intraepithelial neoplasia and those previously pu blished for cervical carcinoma and cervical intraepithelial neoplasia suppo rt the view that these two cancers are analogous and have similar pathogene tic mechanisms. The frequent finding of hypodiploidy in squamous cell hyper plasia and lichen sclerosis next to HPV-negative carcinomas requires furthe r investigation of the molecular pathogenesis of this cancer type.