Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach

Stephanie Craig; Lesley Anderson; Andrew Schache; Michael Moran; Laura Graham; Keith Currie; Keith Rooney; Max Robinson; Navdeep Upile; Rachel Brooker; Mina Mesri; Victoria Bingham; Stephen McQuaid; Terry Jones; Dennis McCance; Manuel Salto-Tellez; Simon McDade; Jacqueline James

doi:10.1038/s41416-019-0414-9

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach

Stephanie Craig, Lesley Anderson, Andrew Schache, Michael Moran, Laura Graham, Keith Currie, Keith Rooney, Max Robinson, Navdeep Upile, Rachel Brooker, Mina Mesri, Victoria Bingham, Stephen McQuaid, Terry Jones, Dennis McCance, Manuel Salto-Tellez, Simon McDade, Jacqueline James

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Abstract

Background
TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients.

Methods
HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV− patients was compared to p16 status.

Results
TNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV− (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16− patients (35%). Cancer stage was reduced in 95% of p16+/HPV− patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37–5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria.

Conclusion
Given the significantly poorer survival of p16+/HPV− OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

Original language	English
Pages (from-to)	827–833
Journal	British Journal of Cancer
Volume	120
DOIs	https://doi.org/10.1038/s41416-019-0414-9
Publication status	Published - 20 Mar 2019

Keywords

OPSCC
HPV
p16 IHC
Staging

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41416-019-0414-9Licence: CC BY

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach
Copyright 2019 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 595 KBLicence: CC BY

Implementation of HPV-specific testing in addition to assessment of p16 expression in oropharyngeal squamous cell carcinoma
Stephanie Craig (Participant), Lesley Anderson (Participant), Andrew Schache (Participant), Michael Moran (Participant), Laura Graham (Participant), Keith Currie (Participant), Keith Rooney (Participant), Max Robinson (Participant), Navdeep Upile (Participant), Rachel Brooker (Participant), Mina Mesri (Participant), Victoria Bingham (Participant), Kate Cuschieri (Participant), Stephen McQuaid (Participant), Terry Jones (Participant), Dennis McCance (Participant), Manuel Salto-Tellez (Participant), Simon McDade (Participant) & Jacqueline James (Participant)
Impact: Health Impact, Quality of Life Impact

Jacqueline James
- j.jamesqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Clinical Professor
- Patrick G Johnston Centre for Cancer Research
Person: Academic

Cite this

Craig, S., Anderson, L., Schache, A., Moran, M., Graham, L., Currie, K., Rooney, K., Robinson, M., Upile, N., Brooker, R., Mesri, M., Bingham, V., McQuaid, S., Jones, T., McCance, D., Salto-Tellez, M., McDade, S., & James, J. (2019). Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach. British Journal of Cancer, 120, 827–833. https://doi.org/10.1038/s41416-019-0414-9

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title = "Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach",

abstract = "BackgroundTNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients.MethodsHPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV− patients was compared to p16 status.ResultsTNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV− (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16− patients (35%). Cancer stage was reduced in 95% of p16+/HPV− patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37–5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria.ConclusionGiven the significantly poorer survival of p16+/HPV− OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.",

keywords = "OPSCC, HPV, p16 IHC, Staging",

author = "Stephanie Craig and Lesley Anderson and Andrew Schache and Michael Moran and Laura Graham and Keith Currie and Keith Rooney and Max Robinson and Navdeep Upile and Rachel Brooker and Mina Mesri and Victoria Bingham and Stephen McQuaid and Terry Jones and Dennis McCance and Manuel Salto-Tellez and Simon McDade and Jacqueline James",

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doi = "10.1038/s41416-019-0414-9",

language = "English",

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Craig, S, Anderson, L, Schache, A, Moran, M, Graham, L, Currie, K, Rooney, K, Robinson, M, Upile, N, Brooker, R, Mesri, M, Bingham, V, McQuaid, S, Jones, T, McCance, D, Salto-Tellez, M , McDade, S & James, J 2019, 'Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach', British Journal of Cancer, vol. 120, pp. 827–833. https://doi.org/10.1038/s41416-019-0414-9

TY - JOUR

T1 - Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach

AU - Craig, Stephanie

AU - Anderson, Lesley

AU - Schache, Andrew

AU - Moran, Michael

AU - Graham, Laura

AU - Currie, Keith

AU - Rooney, Keith

AU - Robinson, Max

AU - Upile, Navdeep

AU - Brooker, Rachel

AU - Mesri, Mina

AU - Bingham, Victoria

AU - McQuaid, Stephen

AU - Jones, Terry

AU - McCance, Dennis

AU - Salto-Tellez, Manuel

AU - McDade, Simon

AU - James, Jacqueline

PY - 2019/3/20

Y1 - 2019/3/20

N2 - BackgroundTNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients.MethodsHPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV− patients was compared to p16 status.ResultsTNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV− (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16− patients (35%). Cancer stage was reduced in 95% of p16+/HPV− patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37–5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria.ConclusionGiven the significantly poorer survival of p16+/HPV− OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

AB - BackgroundTNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients.MethodsHPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV− patients was compared to p16 status.ResultsTNM8 staging was found to improve on TNM7 (log rank p = 0·0190 for TNM8 compared with p = 0·0530 for TNM7) in p16+ patients. Patients who tested p16+ but were HPV− (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16− patients (35%). Cancer stage was reduced in 95% of p16+/HPV− patients despite having a mortality rate twice (HR 2.66 [95% CI: 1.37–5.15]) that of p16+/HPV+ patients under new TNM8 staging criteria.ConclusionGiven the significantly poorer survival of p16+/HPV− OPSCCs, these data provide compelling evidence for use of an HPV-specific test for staging classification. This has particular relevance in light of potential treatment de-escalation that could expose these patients to inappropriately reduced treatment intensity as treatment algorithms evolve.

KW - OPSCC

KW - HPV

KW - p16 IHC

KW - Staging

U2 - 10.1038/s41416-019-0414-9

DO - 10.1038/s41416-019-0414-9

M3 - Article

VL - 120

SP - 827

EP - 833

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

ER -

Recommendations for determining HPV status in patients with oropharyngeal cancers under TNM8 guidelines: a two-tier approach

Abstract

Keywords

UN SDGs

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Impacts

Implementation of HPV-specific testing in addition to assessment of p16 expression in oropharyngeal squamous cell carcinoma

Profiles

Jacqueline James

Cite this