Abstract B176: The correlation of clinicopathologic characteristics with oncogenic somatic mutations and Human Papilloma Virus (HPV) in vulvovaginal carcinoma.
Authors: Clancy Aisling Anne , Sekhon Harmon , Ma Xu , Dimitroulakos Jim , Goss Glenwood , Kanji Femina , Weberpals Johanne 
Published: August 2014

Background: Advanced and recurrent vulvovaginal squamous cell carcinoma (VSCC) is incurable and current treatment with radical surgery and chemotherapy is associated with significant morbidity. Consequently, there is an urgent need for less toxic, more effective targeted systemic therapy. This requires the identification of both prognostic and predictive biomarkers which will drive the selection of the appropriate therapy.

Methods: This is a correlative study of the clinicopathologic characteristics of VSCC patients with tumor Human Papilloma Virus (HPV) status and frequently observed oncogenic somatic mutations. A retrospective review of a cohort of patients at the Ottawa Hospital from 2000 to 2012 is complete including demographics and pathology data. A molecular analysis of tissue samples is being done for HPV status by polymerase chain reaction (PCR) using primers for the L1 region of HPV DNA. Detection of a panel of common somatic mutations (including BRAF, KRAS and EGFR) is being carried out by multiplexed targeted resequencing assay.

Results: Following ethics approval, 81 eligible cases of VSCC were identified with pathologic samples available for analysis. Patient data includes demographic information and clinical outcomes. Forty-seven of the (81) patients had adequate DNA for molecular analysis and were included in the analysis. Samples were DNA-rich with a mean DNA concentration 169 ng/μL (SD 97 ng/μL). The median age at diagnosis was 64 (IQR 56-78) and did not differ between HPV-positive and HPV-negative groups. Overall, 22/47 patients (47%) were HPV-positive and 25/47 (53%) were HPV-negative. Tumor size (3.6±2.4 cm versus 3.9±2.7 cm), lymph node metastases (23% versus 33% with positive nodes) and depth of invasion (6.7±5.4mm versus 9.5±5.7 mm) were not statistically different between HPV-positive and HPV-negative groups respectively. Seventeen of 81 (21%) patients had died from disease, 4 (17%) in the HPV positive and 4 (17%) in the HPV negative groups. The mutational analysis of tumors from the 47 patients in whom DNA is available is ongoing and these results will be presented.

Conclusions: In this retrospective cohort of patients, the incidence of death was unaffected by HPV status. DNA analysis for a mutational marker of prognosis is ongoing and may be determined by mutational aberrations rather than HPV status. Future study should focus on a molecular-targeted approach to the treatment of VSCC.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B176.

Citation Format: Aisling Anne Clancy, Harmon Sekhon, Xu Ma, Jim Dimitroulakos, Glenwood Goss, Femina Kanji, Johanne Weberpals. The correlation of clinicopathologic characteristics with oncogenic somatic mutations and Human Papilloma Virus (HPV) in vulvovaginal carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B176.