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Development And Validation Of A Staging System For HPV-related Oropharyngeal Cancer By The International Collaboration On Oropharyngeal Cancer Network For Staging (ICON-S): A Multicentre Cohort Study.

B O'Sullivan, Shao Hui Huang, Jie Susie Su, Adam S Garden, Erich M Sturgis, Kristina R Dahlstrom, Nancy Y. Lee, Nadeem Riaz, Xin Pei, Shlomo A. Koyfman, David J Adelstein, Brian B. Burkey, Jeppe Friborg, Claus Andrup Kristensen, Anita B Gothelf, Frank Hoebers, Bernd Kremer, Ernst-Jan M. Speel, Daniel W. Bowles, David Raben, Sana D Karam, Eugene Yu, Wei Xu
Published 2016 · Medicine
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BACKGROUND Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. METHODS The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. FINDINGS Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. INTERPRETATION Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. FUNDING None.
This paper references
10.1056/NEJMoa0912217
Human papillomavirus and survival of patients with oropharyngeal cancer.
K Kian Ang (2010)
10.1016/j.oraloncology.2015.02.098
High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer.
Parul Khare Sinha (2015)
Pharynx. In: AJCC cancer staging manual, 7th edn
S Edge (2010)
10.1016/j.ejca.2011.11.036
Radiomics: extracting more information from medical images using advanced feature analysis.
Philippe Lambin (2012)
10.1002/cncr.10567
Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both.
James T. Parsons (2002)
10.1016/j.oraloncology.2014.02.001
Refining risk stratification for locoregional failure after chemoradiotherapy in human papillomavirus-associated oropharyngeal cancer.
Jeffrey M. Vainshtein (2014)
10.1002/hed.21974
p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency.
Adel K. El-Naggar (2012)
10.1053/j.semdp.2015.02.013
HPV-related squamous cell carcinoma of the head and neck: An update on testing in routine pathology practice.
Justin A. Bishop (2015)
on behalf of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis
J Bourhis (2006)
10.3332/ecancer.2016.ed61
The principles of cancer staging
James Brierley (2016)
10.1016/j.radonc.2014.09.005
Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging.
Emmanuel Rios Velazquez (2014)
10.1002/cncr.29402
Changing prognostic significance of tumor stage and nodal stage in patients with squamous cell carcinoma of the oropharynx in the human papillomavirus era.
Florence K. Keane (2015)
Proposal for the 8 th edition of the AJCC / UICC staging system for nasopharyngeal
JJ Pan
10.1016/j.oraloncology.2015.06.014
Correlation of p16 expression and HPV type with survival in oropharyngeal squamous cell cancer.
Sandy Z Liu (2015)
10.1002/9781119013143.CH3
Prognosis and classification of cancer
B O'Sullivan (2015)
10.1016/j.oraloncology.2014.06.008
Patients with low lying lymph nodes are at high risk for distant metastasis in oropharyngeal cancer.
Nadeem Riaz (2014)
10.1200/JCO.2014.58.6412
Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas.
Shao Hui Huang (2015)
10.1097/RCT.0b013e318282d7c3
Intranodal Cystic Changes: A Potential Radiologic Signature/Biomarker to Assess the Human Papillomavirus Status of Cases With Oropharyngeal Malignancies
Ajaykumar C. Morani (2013)
Principles of cancer
LH Sobin (2015)
Prognosis and classifi cation of cancer
B O’Sullivan
10.1016/j.radonc.2010.03.015
Point-of-care outcome assessment in the cancer clinic: audit of data quality.
Karen W Y Wong (2010)
10.1016/j.oraloncology.2012.07.015
Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer.
Shao Hui Huang (2013)
10.1016/S0140-6736(00)90011-4
Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data
Jp Pignon (2000)
10.1002/hed.20796
Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon.
David Goldenberg (2008)
10.1200/JCO.2014.60.1757
Different strokes for different folks: new paradigms for staging oropharynx cancer.
David M. Brizel (2015)
in the era of intensity - modulated radiotherapy
W Xu (2016)
10.1007/978-1-4757-3656-4
AJCC Cancer Staging Manual
Mahul B. Amin (2002)
10.1093/annonc/mds205
Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer.
Angela M. Hong (2013)
10.1016/S0140-6736(06)69121-6
Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis
Jean Bourhis (2006)
Refi ning evaluation methodology on TNM stage system : assessment on HPV - related oropharyngeal cancer
SH Huang (2015)
10.1200/JCO.2011.38.4099
Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer.
Maura L. Gillison (2012)
10.1200/JCO.2012.44.0164
Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis.
B O'Sullivan (2013)
10.1007/978-1-4419-9464-6_8
Head and Neck Cancer Staging and Prognosis: Perspectives of the UICC and the AJCC
Brian O’sullivan (2011)
10.1002/cncr.27727
An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair.
Kristina R Dahlstrom (2013)
10.1002/cncr.29795
Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.
Jian Ji Pan (2016)



This paper is referenced by
Refining The Staging Scheme For Human Papillomavirus-Related Oropharyngeal Carcinoma
Tiange Chen (2016)
Laryngoscope 128 : May 2018
Ashley E. Olson (2018)
10.1002/hed.25504
Radiographic nodal prognostic factors in stage I HPV‐related oropharyngeal squamous cell carcinoma
Onita Bhattasali (2019)
Impact du tabagisme dans les cancers de l’oropharynx HPV-induits
Charlotte Leroy (2018)
10.1002/cncr.32583
Rising incidence of late-stage head and neck cancer in the United States.
Adam Thompson-Harvey (2019)
10.1016/j.canrad.2019.12.003
[Treatment de-intensification strategies for HPV-driven oropharyngeal cancer: A short review].
Chaimaa Lahmamssi (2020)
10.1002/cncr.30588
Human Papillomavirus in Cervical Cancer and Oropharyngeal Cancer: One Cause, Two Diseases
Tara Berman (2017)
[Changes in the new TNM classification in Head and Neck oncology].
Silvia Lambiel (2017)
10.1016/j.ctro.2018.11.009
Ending 40 years of silence: Rationale for a new staging system for soft tissue sarcoma of the head and neck
Ezra Hahn (2019)
10.1007/s11864-019-0688-4
Current Standards for Organ Preservation in Locoregionally Advanced Non-nasopharyngeal Head and Neck Cancer and Evolving Strategies for Favorable-Risk and Platinum-Ineligible Populations
Susan Y. Wu (2019)
10.1200/JCO.18.02424
T-Cell Receptor Gene Therapy for Human Papillomavirus–Associated Epithelial Cancers: A First-in-Human, Phase I/II Study
Stacey L. Doran (2019)
10.1038/nrc.2018.11
The molecular landscape of head and neck cancer
C. René Leemans (2018)
10.1016/S1470-2045(15)00611-7
A TNM classification for HPV+ oropharyngeal cancer.
Sandro Virgilio Porceddu (2016)
10.1186/s41199-016-0016-7
De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer
Yi An (2016)
10.1016/j.oraloncology.2017.03.016
Intravoxel incoherent motion magnetic resonance imaging in head and neck cancer: A systematic review of the diagnostic and prognostic value.
Daniel P Noij (2017)
10.1007/978-3-319-63823-2_11
Human Papillomavirus and Head and Neck Cancer
Shao Hui Huang (2018)
10.1007/s00106-018-0499-0
Staging von Oropharynxkarzinomen
Abbey Beltz (2018)
10.1007/s00405-018-5156-4
The 8th edition AJCC/UICC TNM staging for p16-positive oropharyngeal carcinoma: is there space for improvement?
Shachi Jenny Sharma (2018)
10.3857/roj.2017.00465
Refining prognostic stratification of human papillomavirus-related oropharyngeal squamous cell carcinoma: different prognosis between T1 and T2
Sumin Lee (2017)
10.1007/978-3-030-13936-0_4
Human Papillomavirus Infection and Cancer Risk in Peri- and Postmenopausal Women
Pedro Vieira-Baptista (2019)
10.1016/j.oraloncology.2017.01.012
Oropharyngeal cancer prognosis by tumour HPV status in France: The multicentric Papillophar study.
Jean Lacau Lacau St Guily (2017)
10.1002/hed.24711
Predictors of distant metastasis in human papillomavirus–associated oropharyngeal cancer
Michael A Weller (2017)
10.1016/B978-0-323-26568-3.00033-6
33 – Early HPV-Related Base of Tongue Cancer
Ashish Anilbhai Patel (2018)
10.1055/S-0043-121596
HPV – Das andere Kopf-Hals-Karzinom
Claus Wittekindt (2018)
10.3950/JIBIINKOKA.121.1112
頭頸部癌 TNM 分類の改訂点とその意義
隆一 林 (2018)
Influence de la lymphopénie sur la réponse au Cetuximab en première ligne de chimiothérapie palliative dans les carcinomes épidermoïdes des VADS
Charlotte Prévoteau (2018)
10.1200/JCO.2017.76.2518
Improved Outcome by Adding Concurrent Chemotherapy to Cetuximab and Radiotherapy for Locally Advanced Head and Neck Carcinomas: Results of the GORTEC 2007-01 Phase III Randomized Trial.
Yungan Tao (2018)
10.1371/journal.pbio.2006624
EpCAM ectodomain EpEX is a ligand of EGFR that counteracts EGF-mediated epithelial-mesenchymal transition through modulation of phospho-ERK1/2 in head and neck cancers
Min Pan (2018)
10.1093/jjco/hyz052
A review of head and neck cancer staging system in the TNM classification of malignant tumors (eighth edition).
Nobuya Monden (2019)
10.1002/lary.28059
Extranodal extension is a strong prognosticator in HPV-positive oropharyngeal squamous cell carcinoma.
Eric Bauer (2019)
10.7150/thno.21471
Genomic Analysis of Tumor Microenvironment Immune Types across 14 Solid Cancer Types: Immunotherapeutic Implications
Yu-Pei Chen (2017)
10.1002/cncr.30021
Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas.
Zachary D. Horne (2016)
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