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

Abstract

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.

High levels of p53 expression correlate with DNA aneuploidy in (pre)malignancies of the vulva

“…Our finding of a lack of DNA aneuploidy in LS is coherent with the results published by Scurry et al [16]. They performed cytomorphometric analysis on 20 LS samples and found that 50% of those samples were diploid and that the other 50% were hypoploid.…”

“…In vulvar carcinomas, ploidy has been studied mostly in relation to prognosis; and no results on ploidy status of VIN lesions exist. Despite the limited number of cases in our study, the percentage of DNA aneuploidy in vulvar SCC (9/17, 53%) is in line with the percentages found in previous reports of 13% to 83% [10][11][12][13][14][15][16]. The causal relationship between high p53 expression in vulvar epithelium and DNA aneuploidy remains elusive.…”

“…They performed cytomorphometric analysis on 20 LS samples and found that 50% of those samples were diploid and that the other 50% were hypoploid. The authors concluded that the occurrence of hypoploidy in LS reflects reduced mitotic activity that relates to a loss of DNA [16]. We only found 1 of 9 LS lesions to be DNA hypoploid and have described previously that the proliferative activity in LS is comparable to that in other vulvar premalignancies [26].…”

“…It has been reported that aneuploidy in vulvar carcinomas varies from 13% to 83%, but no relation with prognosis has been described so far [10][11][12][13][14][15][16]. Aneuploidy in vulvar LS varies from 0% to 33% of the cases [14,[16][17][18]. The relation between the expression of cell cycle proteins and ploidy status of vulvar lesions has not been extensively studied.…”

Does lichen sclerosus play a central role in the pathogenesis of human papillomavirus negative vulvar squamous cell carcinoma? The itch-scratch-lichen sclerosus hypothesis

“…In addition to the clinicopathologic differences, recent cytomorphometric and genetic evidence supports the view that HPV-positive and -negative carcinomas are different diseases with different pathogeneses and that unidentified HPV is not the cause of HPVnegative carcinoma. In 12 HPV-positive and 22 HPVnegative vulvar carcinomas, the HPV-positive carcinomas showed a trend for a higher frequency of aneuploidy (83 vs. 59%) and mean DNA index (1.71 vs. 1.41) (18) . Multiploid aneuploid peaks were seen in 75% (9 of 12) of HPV-positive carcinomas, but not in HPV-negative.…”