Angela M Hong1, Peter Ferguson2, Tristan Dodds2, Deanna Jones3, Mengbo Li4, Jean Yang4, Richard A Scolyer2. 1. Central Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW, Australia; Department of Radiation Oncology, Chris O'Brien Lifehouse, NSW, Australia; Melanoma Institute Australia, The University of Sydney, NSW, Australia. Electronic address: angela.hong@sydney.edu.au. 2. Central Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW, Australia; Melanoma Institute Australia, The University of Sydney, NSW, Australia. 3. Central Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW, Australia. 4. School of Mathematics and Statistics, The University of Sydney, NSW, Australia.
Abstract
BACKGROUND: The programmed death pathway plays a role in persistent human papillomavirus (HPV) infection as well as in resistance to immune elimination during malignant progression. In this study, we examined PD-L1 expression by immunohistochemistry and tumour infiltrating lymphocytes (TIL) in 214 patients with oropharyngeal squamous cell cancer (OPSCC) to assess its clinical significance. RESULTS: HPV-positive OPSCC were significantly more likely to express PD-L1 than HPV-negative OPSCC (85.2% vs 57.1%, p < 0.05). PD-L1 staining was more likely to be associated with TILs in HPV-positive OPSCC (67.9% vs 49.6%, p = 0.01). Relative to those patients with HPV-positive/PD-L1-positive OPSCC, patients with HPV negative/PD-L1 negative OPSCC were 6.4 times more likely to develop a local recurrence, 5.8 times more likely to develop an event and 6.5 times more likely to die. Within the HPV positive cases, PD-L1 expression also significantly impacted on the outcomes with PD-L1 negative cases more likely to develop a locoregional recurrence (HR 4.16), to have an event (HR 2.5) and to die (HR 3.16). Evidence of an interaction between HPV status and PD-L1 expression was found for overall survival (p < 0.005). CONCLUSION: Our findings suggested that different immune profiles in oropharyngeal cancer by HPV status and the effect of HPV on the outcomes is modified by PD-L1 expression.
BACKGROUND: The programmed death pathway plays a role in persistent human papillomavirus (HPV) infection as well as in resistance to immune elimination during malignant progression. In this study, we examined PD-L1 expression by immunohistochemistry and tumour infiltrating lymphocytes (TIL) in 214 patients with oropharyngeal squamous cell cancer (OPSCC) to assess its clinical significance. RESULTS:HPV-positive OPSCC were significantly more likely to express PD-L1 than HPV-negative OPSCC (85.2% vs 57.1%, p < 0.05). PD-L1 staining was more likely to be associated with TILs in HPV-positive OPSCC (67.9% vs 49.6%, p = 0.01). Relative to those patients with HPV-positive/PD-L1-positive OPSCC, patients with HPV negative/PD-L1 negative OPSCC were 6.4 times more likely to develop a local recurrence, 5.8 times more likely to develop an event and 6.5 times more likely to die. Within the HPV positive cases, PD-L1 expression also significantly impacted on the outcomes with PD-L1 negative cases more likely to develop a locoregional recurrence (HR 4.16), to have an event (HR 2.5) and to die (HR 3.16). Evidence of an interaction between HPV status and PD-L1 expression was found for overall survival (p < 0.005). CONCLUSION: Our findings suggested that different immune profiles in oropharyngeal cancer by HPV status and the effect of HPV on the outcomes is modified by PD-L1 expression.
Authors: Nora Wuerdemann; Sibel E Gültekin; Katharina Pütz; Claus Wittekindt; Christian U Huebbers; Shachi J Sharma; Hans Eckel; Anna B Schubotz; Stefan Gattenlöhner; Reinhard Büttner; Ernst-Jan Speel; Jens P Klussmann; Steffen Wagner; Alexander Quaas Journal: Int J Mol Sci Date: 2020-07-23 Impact factor: 5.923