TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma

Christian von Buchwald; Kathrine Kronberg Jakobsen; Amanda-Louise Fenger Carlander; Sara Tous; Christian Grønhøj; Jacob H Rasmussen; Jill Brooks; Miren Taberna; Marisa Mena; Francisca Morey; Laia Bruni; Nikolaos Batis; Ruud H Brakenhoff; C René Leemans; Robert J Baatenburg de Jong; Jens Peter Klussmann; Nora Wuerdemann; Steffen Wagner; Tina Dalianis; Linda Marklund; Haïtham Mirghani; Andrew Schache; Jaqueline A James; Shao Hui Huang; Brian O'Sullivan; Paul Nankivell; Martina A Broglie; Markus Hoffmann; Elgar Susanne Quabius; Lesley A Anderson; Stephanie G Craig; Laia Alemany; Hisham Mehanna; HNCIG-EPIC group

doi:10.1016/j.ejca.2024.114329

TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma

Christian von Buchwald, Kathrine Kronberg Jakobsen, Amanda-Louise Fenger Carlander, Sara Tous, Christian Grønhøj, Jacob H Rasmussen, Jill Brooks, Miren Taberna, Marisa Mena, Francisca Morey, Laia Bruni, Nikolaos Batis, Ruud H Brakenhoff, C René Leemans, Robert J Baatenburg de Jong, Jens Peter Klussmann, Nora Wuerdemann, Steffen Wagner, Tina Dalianis, Linda MarklundHaïtham Mirghani, Andrew Schache, Jaqueline A James, Shao Hui Huang, Brian O'Sullivan, Paul Nankivell, Martina A Broglie, Markus Hoffmann, Elgar Susanne Quabius, Lesley A Anderson, Stephanie G Craig, Laia Alemany, Hisham Mehanna, HNCIG-EPIC group

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis.

METHODS: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region.

RESULTS: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability.

CONCLUSION: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.

Original language	English
Article number	114329
Journal	European Journal of Cancer
Volume	211
Early online date	12 Sept 2024
DOIs	https://doi.org/10.1016/j.ejca.2024.114329
Publication status	Early online date - 12 Sept 2024

Bibliographical note

Keywords

Humans
Oropharyngeal Neoplasms/virology
Male
Cyclin-Dependent Kinase Inhibitor p16/metabolism
Female
Middle Aged
Neoplasm Staging
Aged
Retrospective Studies
Papillomavirus Infections/virology
Prospective Studies
Prognosis
Carcinoma, Squamous Cell/virology
Squamous Cell Carcinoma of Head and Neck/virology
Adult
Papillomaviridae/isolation & purification

UN SDGs

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

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von Buchwald, C., Jakobsen, K. K., Carlander, A.-L. F., Tous, S., Grønhøj, C., Rasmussen, J. H., Brooks, J., Taberna, M., Mena, M., Morey, F., Bruni, L., Batis, N., Brakenhoff, R. H., René Leemans, C., Jong, R. J. B. D., Klussmann, J. P., Wuerdemann, N., Wagner, S., Dalianis, T., ... HNCIG-EPIC group (2024). TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma. European Journal of Cancer, 211, Article 114329. Advance online publication. https://doi.org/10.1016/j.ejca.2024.114329

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title = "TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma",

abstract = "PURPOSE: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis.METHODS: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region.RESULTS: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability.CONCLUSION: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.",

keywords = "Humans, Oropharyngeal Neoplasms/virology, Male, Cyclin-Dependent Kinase Inhibitor p16/metabolism, Female, Middle Aged, Neoplasm Staging, Aged, Retrospective Studies, Papillomavirus Infections/virology, Prospective Studies, Prognosis, Carcinoma, Squamous Cell/virology, Squamous Cell Carcinoma of Head and Neck/virology, Adult, Papillomaviridae/isolation & purification",

author = "{von Buchwald}, Christian and Jakobsen, {Kathrine Kronberg} and Carlander, {Amanda-Louise Fenger} and Sara Tous and Christian Gr{\o}nh{\o}j and Rasmussen, {Jacob H} and Jill Brooks and Miren Taberna and Marisa Mena and Francisca Morey and Laia Bruni and Nikolaos Batis and Brakenhoff, {Ruud H} and {Ren{\'e} Leemans}, C and Jong, {Robert J Baatenburg de} and Klussmann, {Jens Peter} and Nora Wuerdemann and Steffen Wagner and Tina Dalianis and Linda Marklund and Ha{\"i}tham Mirghani and Andrew Schache and James, {Jaqueline A} and Huang, {Shao Hui} and Brian O'Sullivan and Paul Nankivell and Broglie, {Martina A} and Markus Hoffmann and Quabius, {Elgar Susanne} and Anderson, {Lesley A} and Craig, {Stephanie G} and Laia Alemany and Hisham Mehanna and {HNCIG-EPIC group}",

year = "2024",

month = sep,

day = "12",

doi = "10.1016/j.ejca.2024.114329",

language = "English",

volume = "211",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier",

}

von Buchwald, C, Jakobsen, KK, Carlander, A-LF, Tous, S, Grønhøj, C, Rasmussen, JH, Brooks, J, Taberna, M, Mena, M, Morey, F, Bruni, L, Batis, N, Brakenhoff, RH, René Leemans, C, Jong, RJBD, Klussmann, JP, Wuerdemann, N, Wagner, S, Dalianis, T, Marklund, L, Mirghani, H, Schache, A, James, JA, Huang, SH, O'Sullivan, B, Nankivell, P, Broglie, MA, Hoffmann, M, Quabius, ES, Anderson, LA, Craig, SG, Alemany, L, Mehanna, H & HNCIG-EPIC group 2024, 'TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma', European Journal of Cancer, vol. 211, 114329. https://doi.org/10.1016/j.ejca.2024.114329

TY - JOUR

T1 - TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma

AU - von Buchwald, Christian

AU - Jakobsen, Kathrine Kronberg

AU - Carlander, Amanda-Louise Fenger

AU - Tous, Sara

AU - Grønhøj, Christian

AU - Rasmussen, Jacob H

AU - Brooks, Jill

AU - Taberna, Miren

AU - Mena, Marisa

AU - Morey, Francisca

AU - Bruni, Laia

AU - Batis, Nikolaos

AU - Brakenhoff, Ruud H

AU - René Leemans, C

AU - Jong, Robert J Baatenburg de

AU - Klussmann, Jens Peter

AU - Wuerdemann, Nora

AU - Wagner, Steffen

AU - Dalianis, Tina

AU - Marklund, Linda

AU - Mirghani, Haïtham

AU - Schache, Andrew

AU - James, Jaqueline A

AU - Huang, Shao Hui

AU - O'Sullivan, Brian

AU - Nankivell, Paul

AU - Broglie, Martina A

AU - Hoffmann, Markus

AU - Quabius, Elgar Susanne

AU - Anderson, Lesley A

AU - Craig, Stephanie G

AU - Alemany, Laia

AU - Mehanna, Hisham

AU - HNCIG-EPIC group

PY - 2024/9/12

Y1 - 2024/9/12

N2 - PURPOSE: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis.METHODS: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region.RESULTS: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability.CONCLUSION: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.

AB - PURPOSE: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis.METHODS: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region.RESULTS: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability.CONCLUSION: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis.

KW - Humans

KW - Oropharyngeal Neoplasms/virology

KW - Male

KW - Cyclin-Dependent Kinase Inhibitor p16/metabolism

KW - Female

KW - Middle Aged

KW - Neoplasm Staging

KW - Aged

KW - Retrospective Studies

KW - Papillomavirus Infections/virology

KW - Prospective Studies

KW - Prognosis

KW - Carcinoma, Squamous Cell/virology

KW - Squamous Cell Carcinoma of Head and Neck/virology

KW - Adult

KW - Papillomaviridae/isolation & purification

U2 - 10.1016/j.ejca.2024.114329

DO - 10.1016/j.ejca.2024.114329

M3 - Article

C2 - 39293346

SN - 0959-8049

VL - 211

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 114329

ER -

TNM 8 staging system beyond p16: Double HPV/p16 status is superior to p16 alone in predicting outcome in oropharyngeal squamous cell carcinoma

Abstract

Bibliographical note

Keywords

UN SDGs

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