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Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer

Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer
Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer
Background: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.

Methods: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.

Results: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TILhigh=96%, HPV-positive/TILlow=59%). Survival of HPV-positive/TILlow patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a ‘training’ cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82).

Interpretation: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.
0007-0920
489-500
Ward, M.J.
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Mellows, T.
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Riley, C.
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Harris, S.
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Suchak, K.
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Webb, A.
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Hampton, C.
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Patel, N.N.
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Randall, C.J.
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Cox, H.J.
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Jogai, S.
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Primrose, J.
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Piper, K.
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Ottensmeier, C.H.
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King, E.V.
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Thomas, Gareth J.
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Ward, M.J.
a199bc96-75b6-415c-bffe-e68e8a00b468
Mellows, T.
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Riley, C.
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Harris, S.
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Suchak, K.
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Webb, A.
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Hampton, C.
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Patel, N.N.
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Randall, C.J.
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Cox, H.J.
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Jogai, S.
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Primrose, J.
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Piper, K.
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Ottensmeier, C.H.
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King, E.V.
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Thomas, Gareth J.
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Ward, M.J., Mellows, T., Riley, C., Harris, S., Suchak, K., Webb, A., Hampton, C., Patel, N.N., Randall, C.J., Cox, H.J., Jogai, S., Primrose, J., Piper, K., Ottensmeier, C.H., King, E.V. and Thomas, Gareth J. (2013) Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. British Journal of Cancer, 110, 489-500. (doi:10.1038/bjc.2013.639). (PMID:24169344)

Record type: Article

Abstract

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.

Methods: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.

Results: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TILhigh=96%, HPV-positive/TILlow=59%). Survival of HPV-positive/TILlow patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a ‘training’ cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82).

Interpretation: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

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Accepted/In Press date: 12 September 2013
Published date: 29 October 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 359539
URI: http://eprints.soton.ac.uk/id/eprint/359539
ISSN: 0007-0920
PURE UUID: 81b475e6-c215-4729-8f30-c0d350569664
ORCID for J. Primrose: ORCID iD orcid.org/0000-0002-2069-7605

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Date deposited: 06 Nov 2013 14:26
Last modified: 15 Mar 2024 02:47

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Contributors

Author: M.J. Ward
Author: T. Mellows
Author: C. Riley
Author: S. Harris
Author: K. Suchak
Author: A. Webb
Author: C. Hampton
Author: N.N. Patel
Author: C.J. Randall
Author: H.J. Cox
Author: S. Jogai
Author: J. Primrose ORCID iD
Author: K. Piper
Author: E.V. King

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