Mererid Evans, Chris Hurt, Rhian Rhys, Abhishek Mahajan, Andrew McQueen, Joanna Dixon, Max Robinson, Neil Robinson, Keith D. Hunter, Adam Christian, Adam Jones, Aline Queiroz, Shao Hui Huang, Brian O’Sullivan, Joanna Canham, Christie Heiberg, Terry E. Jones
BACKGROUND: Imaging-detected and pathological extranodal extension (iENE, pENE) negatively impact prognosis in Human Papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC), as reflected in future TNM staging updates. Correlation between iENE and pENE in HPV-positive OPSCC is currently unknown yet is vital to determine how iENE should be used to influence treatment decisions. METHODS: PATHOS is a trial of de-intensified adjuvant treatment after transoral surgery for HPV-positive OPSCC. 291 consecutively recruited patients undergoing surgery at three UK centres were included. Pre-operative cross-sectional imaging (CT and/or MRI) was independently scored for iENE by 2 expert radiologists; pENE was scored by 2 expert pathologists. RESULTS: Inter-rater agreement for iENE was fair in round 1 (Gwet's AC: 0.34 (95%CI:0.26-0.41)) but improved to very good after second review (Gwet's AC: 0.88 (95%CI:0.85-0.93), Agreement: 0.91 (95%CI:0.87-0.94)). Sensitivity of iENE for predicting pENE was relatively low (at best: 56.4% (95%CI:42.3-69.7) and specificity was high (at worst: 70.9% (95%CI:65.0-76.3)). Excluding cases with suboptimal image quality and recent core biopsy produced modest improvements in sensitivity (up to 59.4% (95%CI:40.6-76.3)) and specificity (up to 87.8% (95%CI:80.4-93.2)). DISCUSSION: The high specificity could help select iENE-negative patients for surgery, but higher sensitivity is required before excluding surgery based solely on iENE positivity.