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Correlation between imaging-detected and pathological extranodal extension in a randomised trial in Human Papillomavirus-positive oropharyngeal cancer

Correlation between imaging-detected and pathological extranodal extension in a randomised trial in Human Papillomavirus-positive oropharyngeal cancer
Correlation between imaging-detected and pathological extranodal extension in a randomised trial in Human Papillomavirus-positive oropharyngeal cancer
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.
0007-0920
Evans, Mererid
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Hurt, Chris
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Rhys, Rhian
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Mahajan, Abhishek
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McQueen, Andrew
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Dixon, Joanna
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Robinson, Max
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Robinson, Neil
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Hunter, Keith
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Christian, Adam
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Jones, Adam
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Queiroz, Aline
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Huang, Shao Hui
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O’Sullivan, Brian
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Canham, Joanna
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Heiberg, Christie
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Jones, Terry
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Evans, Mererid
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Hurt, Chris
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Rhys, Rhian
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Mahajan, Abhishek
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McQueen, Andrew
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Dixon, Joanna
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Robinson, Max
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Robinson, Neil
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Hunter, Keith
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Christian, Adam
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Jones, Adam
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Queiroz, Aline
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Huang, Shao Hui
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O’Sullivan, Brian
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Canham, Joanna
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Heiberg, Christie
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Jones, Terry
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Evans, Mererid, Hurt, Chris, Rhys, Rhian, Mahajan, Abhishek, McQueen, Andrew, Dixon, Joanna, Robinson, Max, Robinson, Neil, Hunter, Keith, Christian, Adam, Jones, Adam, Queiroz, Aline, Huang, Shao Hui, O’Sullivan, Brian, Canham, Joanna, Heiberg, Christie and Jones, Terry (2025) Correlation between imaging-detected and pathological extranodal extension in a randomised trial in Human Papillomavirus-positive oropharyngeal cancer. British Journal of Cancer. (doi:10.1038/s41416-025-03291-z).

Record type: Article

Abstract

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.

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Accepted/In Press date: 14 November 2025
Published date: 27 November 2025
Additional Information: Publisher Copyright: © The Author(s) 2025.

Identifiers

Local EPrints ID: 507457
URI: http://eprints.soton.ac.uk/id/eprint/507457
ISSN: 0007-0920
PURE UUID: 4706e72e-8a2f-4c06-a264-a48a2361760e
ORCID for Chris Hurt: ORCID iD orcid.org/0000-0003-1206-8355

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Date deposited: 09 Dec 2025 17:54
Last modified: 10 Dec 2025 03:05

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Contributors

Author: Mererid Evans
Author: Chris Hurt ORCID iD
Author: Rhian Rhys
Author: Abhishek Mahajan
Author: Andrew McQueen
Author: Joanna Dixon
Author: Max Robinson
Author: Neil Robinson
Author: Keith Hunter
Author: Adam Christian
Author: Adam Jones
Author: Aline Queiroz
Author: Shao Hui Huang
Author: Brian O’Sullivan
Author: Joanna Canham
Author: Christie Heiberg
Author: Terry Jones

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