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Observational Study
. 2021 Oct 27:5:PO.21.00094.
doi: 10.1200/PO.21.00094. eCollection 2021.

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

Stefano Cavalieri  1 , Mara S Serafini  2 , Andrea Carenzo  2 , Silvana Canevari  3 , Ruud H Brakenhoff  4 , C René Leemans  4 , Irene H Nauta  4 , Frank Hoebers  5 , Mari F C M van den Hout  6 , Kathrin Scheckenbach  7 , Thomas K Hoffmann  8 , Laura Ardighieri  9 , Tito Poli  10 , Pasquale Quattrone  11 , Laura D Locati  1 , Lisa Licitra  1   12 , Loris De Cecco  2
Affiliations
Observational Study

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

Stefano Cavalieri et al. JCO Precis Oncol. .

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.

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Conflict of interest statement

Loris De Cecco Research Funding: Bristol Myers Squibb Foundation No other potential conflicts of interest were reported. Loris De Cecco Research Funding: Bristol Myers Squibb Foundation No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Selection of the final data set. HPV, human papillomavirus; OPSCC, oropharyngeal squamous cell carcinoma.
FIG 2.
FIG 2.
Prognostic analysis of the final data set (n = 235): (A) OS evaluation according to the three-cluster model; (B) OS according to TNM, 8th edition; (C) Alluvial diagram; and (D) OS of the 185 ENE-negative cases. ENE, extranodal extension; OS, overall survival; TNM, tumor-node-metastasis.
FIG 3.
FIG 3.
HPV-clustering models applied to the final data set subdivided in the three-cluster model: (A) box plot of Slebos-UP score, (B) box plot of Pyeon-UP score, and (C) box plot of Zhang score. HPV, human papillomavirus.
FIG 4.
FIG 4.
Immune or functional characterization of the three clusters by xCell and Hallmarks: (A) box plot of immune score, (B) box plot of stroma score, and (C) summary of enriched Hallmark gene set for the three-cluster pairwise comparisons.
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