6th ICHNO Abstract Book

6th ICHNO 6 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 16 – 18 March 2017 Barcelona, Spain __________________________________________________________________________________________ page 51

Purpose or Objective In oropharyngeal squamous cell carcinoma (OPSCC), high- risk human papilloma virus (HR-HPV) infection is associated with deregulated expression of cell cycle associated proteins, including cyclin D1 and pRb. Based on studies analysing patient cohorts with predominantly advanced tumour stages and heterogeneous treatment modalities, Cyclin D1 and pRb overexpression has been linked to poor prognosis in OPSCC.The objective of our study was to evaluate the prognostic significance of cyclin D1 and pRb expression in surgically treated OPSCC patients. Material and Methods Retrospective analysis of clinicopathological characteristics of surgically treated OPSCC patients was performed. Tumour tissue samples were tested for HR- HPV DNA using PCR. Cyclin D1, pRb and p16 immunohistochemistry were performed using OPSCC tissue microarrays and were scored positive if more than 25% (Cyclin D1, pRb) and 70% (p16) of tumour cells stained positive, respectively. Overall survival (OS) and disease- specific survival (DSS) were analysed by Kaplan-Meier curves and log-rank test. The prognostic significance of cyclin D1 and pRb expression was assessed by uni- and multivariate cox regression analysis, adjusted for established prognostic factors. Results 322 OPSCC patients treated with surgery alone (n=110) or surgery with adjuvant radio-(chemo) therapy (n=212) were included in the analysis. Cyclin D1 and pRb expression was found in 42% and 49% of tumours, respectively. 48% of OPSCC had a positive HR-HPV status defined as the combined positivity for HR-HPV DNA and p16 expression. Cyclin D1and pRb was inversely correlated with tumoral HR-HPV status (p<0.001). Cyclin D1 expression of tumour cells was associated with reduced 5-year OS (81.2% versus 66.7%, p=0.01) and DSS (87.8% versus 80.6%, p=0.03). This result was even more pronounced with pRb expression5- year OS (85% versus 67%, p=0.0001) and DSS (92% versus 77%, p=0.0001) In multivariate analysis, including tumour stage, HR-HPV status and smoking history, cyclin D1 and pRb expression lost its prognostic Impact whereas only tumoral HR-HPV status positively influenced survival. Conclusion Cyclin D1 protein and pRb expression is inversely correlated with tumour HR-HPV positivity and may serve as a diagnostic and prognostic marker in OPSCC patients in addition to the HR-HPV status. Acknowledgement: This study was supported by the Swiss Cancer League. The authors appreciate the contribution of the other investigators of the Swiss Cohort of Oropharyngeal Cancer Patients (SCOC). PO-107 Clinical outcomes of HPV-positive non- oropharyngeal squamous cell carcinoma: analysis of the NCDB H. Ko 1 , R. Sacotte 2 , M. Yu 1 , S. Chen 1 , A. Wieland 1 , M. Witek 1 1 Univ. of Wisconsin School of Medicine and Public H, Human Oncology, Madison WI, USA 2 Northwestern University, Feinberg School of Medicine, Chicago, USA Purpose or Objective The favorable prognosis of patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is well established. Conversely, the clinical significance of HPV- positive non-OPSCC is controversial. We sought to describe patient characteristics and clinical outcomes for HPV-positive non-OPSCC using the National Cancer Database (NCDB).

hypothesised an element of age bias in relation to determining p16 status, and questioned its justification. Despite Public Health efforts reducing tobacco consumption, a well-recognised causal agent of OPSCC, the expected decrease in OPSCC incidence was only brief, before resurging dramatically. In the United States alone, the percentage of OPSCC p16 positive cases has risen from 16% in 1989 to over 70% in 2004 3 , whilst studies in Scandinavia have suggested HPV becoming the sole progenitor of OPSCC, foreboding a virus-induced 75 cases of OPSCC admitted to our Centre in 2015, were identified using CaPPs (Cancer Patient Pathway System). Using Electronic Care Records, 67 (89%) of these cases had p16 status confirmed either on initial or secondary testing. Results Of the 67 cases tested, 37 (55%) were p16 positive. Of these 37 p16 positive cases, 78% were male, with 65% being males aged 40-69, compared with 16% females aged 40-69. This is comparable with evidence that p16 positive OPSCC is a disease of the middle-aged male 5 . All cases were ethnically white. There was evidence of age bias in our Centre in relation to determining p16 status from age 60 onwards. Per decade there was a step-wise percentage reduction of OPSCC cases being stratified by p16 status. Of the total OPSCC cohort tested: 100% aged 30-59 were tested; 91% aged 60-69; 80% of ages 70-79; and only 50% of those over 80 were tested. However, this was followed by a comparable step-wise decrease in p16 positive incidence per decade also, from 100% in cases aged 40-49, 60% aged 50-59, to 33% aged over 80. Incidentally, the youngest case of p16 positivity was a 32-yr-old female, the eldest an 85-yr-old male. The youngest p16 negative case was a 50-yr-old male. carcinoma epidemic 4 . Material and Methods

Conclusion Despite a decreasing incidence of HPV p16 positivity with older age, there were nonetheless cases of such identified in our cohort. We know that p16 status is associated with a better prognosis, especially when other risk factors such as tobacco and alcohol are less. As tobacco consumption decreases, the increasing primacy of OPSCC p16 positivity will endure. With trials underway on therapy de- intensification, there is a duty to assess all OPSCC for p16 status to offer the opportunity for prognostic discussion and the possibility of older patients to be represented in these trials. We feel there is justification to test all OPSCC for p16 status. PO-106 Prognostic significance of cyclin D1 and pRb expression in oropharyngeal carcinoma M.A. Broglie 1 , M.M. Plath 1 , S.J. Stoeckli 1 , W. Jochum 2 1 Kantonsspital St. Gallen, Otorhinolaryngology- Head and Neck Surgery, St Gallen, Switzerland 2 Kantonsspital St. Gallen, Institute of Pathology, St Gallen, Switzerland