Abstract 5050: Molecular heterogeneity in HPV-dependent and -independent vulvar carcinogenesis: Chromosome 1 gain reflects the cancer risk in vulvar intraepithelial neoplasia

Abstract

Abstract Vulvar squamous cell carcinoma (VSCC) and precancerous high-grade vulvar intraepithelial neoplasia (VIN) can develop through human papillomavirus (HPV)-dependent and -independent pathways, indicating a heterogeneous disease. Only a minority of VIN progress, but current clinical and histological classifications are insufficient to predict the cancer risk. Here we analyzed copy number alterations (CNA) to assess the molecular heterogeneity of vulvar lesions in relation to HPV and cancer risk. HPV-status and CNA by means of whole-genome next-generation shallow-sequencing were assessed in 24 VSCC and 41 VIN lesions. The latter included VIN of women with associated VSCC (VINVSCC) and women who did not develop VSCC during >10 year follow-up (VINnoVSCC). HPV-testing resulted in 41 HPV-positive lesions (16 VINVSCC, 14 VINnoVSCC and 11 VSCC) and 24 HPV-negative lesions (11 VINVSCC and 13 VSCC). HPV-positive and -negative VSCC showed a partially overlapping pattern of recurrent CNA, including frequent gains of 3q and 8q. In contrast, amplification of 11q13/cyclinD1 was exclusively found in HPV-negative lesions. HPV-negative VINVSCC had less CNA than VSCC (P = 0.009), mainly 8q gains and 8p losses. In HPV-positive lesions, CNA frequencies were lower in VINnoVSCC than in VINVSCC (P = 0.022) and VSCC. Interestingly, a 1pq gain was detected in 81% of VINVSCC and only 29% of VINnoVSCC. In conclusion, HPV-dependent and -independent vulvar carcinogenesis is characterized by distinct CNA patterns at the VIN stage, while more comparable patterns are present at the cancer stage. Progression risk in VIN is reflected by the extent of CNA, in particularly chromosome 1 gain. Citation Format: Maaike CG Bleeker, Dorian RA Swarts, Quirinus JM Voorham, Saskia M. Wilting, Marc van Beurden, Renske DM Steenbergen. Molecular heterogeneity in HPV-dependent and -independent vulvar carcinogenesis: Chromosome 1 gain reflects the cancer risk in vulvar intraepithelial neoplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5050.