Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma

Stefano Cavalieri; Mara S Serafini; Andrea Carenzo; Silvana Canevari; Ruud H Brakenhoff; René C Leemans; Irene H Nauta; Frank Hoebers; Mari F C M van den Hout; Kathrin Scheckenbach; Thomas K Hoffmann; Laura Ardighieri; Tito Poli; Pasquale Quattrone; Laura D Locati; Lisa Licitra; Loris De Cecco

doi:10.1200/PO.21.00094

Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma

Stefano Cavalieri, Mara S Serafini, Andrea Carenzo, Silvana Canevari, Ruud H Brakenhoff, René C Leemans, Irene H Nauta, Frank Hoebers, Mari F C M van den Hout, Kathrin Scheckenbach, Thomas K Hoffmann, Laura Ardighieri, Tito Poli, Pasquale Quattrone, Laura D Locati, Lisa Licitra, Loris De Cecco^*

^*Corresponding author for this work

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

Abstract

Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.

METHODS: Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.

RESULTS: The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.

CONCLUSION: The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

Original language	English
Pages (from-to)	1666-1676
Number of pages	11
Journal	JCO Precision Oncology
Volume	5
DOIs	https://doi.org/10.1200/PO.21.00094
Publication status	Published - May 2021

Keywords

HEAD
HPV
METAANALYSIS
NECK CANCERS
SUBTYPES
SURVIVAL

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Cavalieri, S., Serafini, M. S., Carenzo, A., Canevari, S., Brakenhoff, R. H., Leemans, R. C., Nauta, I. H., Hoebers, F., van den Hout, M. F. C. M., Scheckenbach, K., Hoffmann, T. K., Ardighieri, L., Poli, T., Quattrone, P., Locati, L. D., Licitra, L., & De Cecco, L. (2021). Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma. JCO Precision Oncology, 5, 1666-1676. https://doi.org/10.1200/PO.21.00094

@article{17f812ffdd4b47b58d1649843ec02818,

title = "Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma",

abstract = "Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODS: Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTS: The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSION: The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.",

keywords = "HEAD, HPV, METAANALYSIS, NECK CANCERS, SUBTYPES, SURVIVAL",

author = "Stefano Cavalieri and Serafini, {Mara S} and Andrea Carenzo and Silvana Canevari and Brakenhoff, {Ruud H} and Leemans, {Ren{\'e} C} and Nauta, {Irene H} and Frank Hoebers and {van den Hout}, {Mari F C M} and Kathrin Scheckenbach and Hoffmann, {Thomas K} and Laura Ardighieri and Tito Poli and Pasquale Quattrone and Locati, {Laura D} and Lisa Licitra and {De Cecco}, Loris",

note = "{\textcopyright} 2021 by American Society of Clinical Oncology.",

year = "2021",

month = may,

doi = "10.1200/PO.21.00094",

language = "English",

volume = "5",

pages = "1666--1676",

journal = "JCO Precision Oncology",

issn = "2473-4284",

publisher = "American Society of Clinical Oncology",

}

Cavalieri, S, Serafini, MS, Carenzo, A, Canevari, S, Brakenhoff, RH, Leemans, RC, Nauta, IH, Hoebers, F , van den Hout, MFCM, Scheckenbach, K, Hoffmann, TK, Ardighieri, L, Poli, T, Quattrone, P, Locati, LD, Licitra, L & De Cecco, L 2021, 'Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma', JCO Precision Oncology, vol. 5, pp. 1666-1676. https://doi.org/10.1200/PO.21.00094

TY - JOUR

T1 - Clinical Validity of a Prognostic Gene Expression Cluster-Based Model in Human Papillomavirus-Positive Oropharyngeal Carcinoma

AU - Cavalieri, Stefano

AU - Serafini, Mara S

AU - Carenzo, Andrea

AU - Canevari, Silvana

AU - Brakenhoff, Ruud H

AU - Leemans, René C

AU - Nauta, Irene H

AU - Hoebers, Frank

AU - van den Hout, Mari F C M

AU - Scheckenbach, Kathrin

AU - Hoffmann, Thomas K

AU - Ardighieri, Laura

AU - Poli, Tito

AU - Quattrone, Pasquale

AU - Locati, Laura D

AU - Licitra, Lisa

AU - De Cecco, Loris

PY - 2021/5

Y1 - 2021/5

N2 - Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODS: Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTS: The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSION: The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

AB - Under common therapeutic regimens, the prognosis of human papillomavirus (HPV)-positive squamous oropharyngeal carcinomas (OPCs) is more favorable than HPV-negative OPCs. However, the prognosis of some tumors is dismal, and validated prognostic factors are missing in clinical practice. The present work aimed to validate the prognostic significance of our published three-cluster model and to compare its prognostic value with those of the 8th edition of the tumor-node-metastasis staging system (TNM8) and published signatures and clustering models.METHODS: Patients with HPV DNA-positive OPCs with locoregionally advanced nonmetastatic disease treated with curative intent (BD2Decide observational study, NCT02832102) were considered as validation cohort. Patients were treated in seven European centers, with expertise in the multidisciplinary management of patients with head and neck cancer. The median follow-up was 46.2 months (95% CI, 41.2 to 50), and data collection was concluded in September 2019. The primary end point of this study was overall survival (OS). Three-clustering models and seven prognostic signatures were compared with our three-cluster model.RESULTS: The study population consisted of 235 patients. The three-cluster model confirmed its prognostic value. Two-year OS in each cluster was 100% in the low-risk cluster, 96.6% in the intermediate-risk cluster, and 86.3% in the high-risk cluster (P = .00074). For the high-risk cluster, we observed an area under the curve = 0.832 for 2-year OS, significantly outperforming TNM 8th edition (area under the curve = 0.596), and functional and biological differences were identified for each cluster.CONCLUSION: The rigorous clinical selection of the cases included in this study confirmed the robustness of our three-cluster model in HPV-positive OPCs. The prognostic value was found to be independent and superior compared with TNM8. The next step includes the translation of the three-cluster model in clinical practice. This could open the way to future exploration of already available therapies in HPV-positive OPCs tailoring de-escalation or intensification according to the three-cluster model.

KW - HEAD

KW - HPV

KW - METAANALYSIS

KW - NECK CANCERS

KW - SUBTYPES

KW - SURVIVAL

U2 - 10.1200/PO.21.00094

DO - 10.1200/PO.21.00094

M3 - Article

C2 - 34738049

SN - 2473-4284

VL - 5

SP - 1666

EP - 1676

JO - JCO Precision Oncology

JF - JCO Precision Oncology

ER -