899P - Defining the genomic landscape of vulvar squamous cell carcinoma (VSCC) using next generation sequencing: the role of HPV infection

Abstract

Surgery for vulvar squamous cell carcinoma (VSCC) is associated with physical and psychological morbidity. Targeted therapies have not influenced outcomes, in part because the genomic landscape of VSCC remains incompletely understood and is complicated by two etiologies: HPV-dependent and HPV-independent disease. Next-generation sequencing (NGS) was used to identify somatic mutations by HPV status (+/-). We conducted a retrospective review of patients (pts) seen at the Ottawa Hospital, Ottawa, Canada between 2000-2012 for VSCC. Clinical and pathological data was collected and pts with adequate tumor for HPV and molecular analysis were identified. HPV status was determined by polymerase chain reaction (PCR) with primers targeting the L1 region of HPV DNA. The Ion AmpliSeq™ Cancer Hotspot Panel v2 is being used to examine the presence of 50 known mutations. Forty-seven pts with VSCC were included. 22/47 (47%) were HPV+ and 25/47 (53%) were HPV-. Median age at diagnosis was 60 years (IQR 49-76) and 69 years (IQR 58-77), for HPV+ and HPV-, respectively. Disease stage by HPV status (+ vs -) was: I (15 vs 16), II (2 vs 0), III (2 vs 9) and IV (3 vs 0). Molecular data is available on 31 pts (17 HPV + , 14 HPV-). Among HPV+ pts, 15/17 had ≥ 1 mutation. Mutational frequencies among HPV+ pts were: TP53 7/17, PIK3CA 6/17, KDR 5/17, KIT: 3/17, FGFR3 3/17, and one mutation each of PTEN, CTNNB1, APC, KRAS, ERBB4, ATM, SMARCB1, FLT3, CDK2A. Among the HPV- pts, 12/14 had ≥ 1 mutation. Mutational frequencies among HPV- pts were: TP53 8/14, HRAS 3/14, CDKN2A 2/14, PI3KCA 2/14, KDR 1/14 and GNA11 1/14. VSCC is characterized by a high mutation rate and a high prevalence of HPV infection. HPV-dependent and HPV-independent disease have unique mutational profiles. The high prevalence of “actionable” mutations supports the need for trials of targeted therapies. Molecular data on the full study cohort (n = 47) will be presented.