1. Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma.
- Author
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Suchan M, Wuerdemann N, Wagner S, Langer C, Arens C, Johannsen J, Prinz J, Sharma SJ, Charpentier A, Mayer M, Klasen C, Zimmermann P, Eckel H, Kopp C, Huebbers CU, Klein S, Siemanowski J, Meinel J, Klussmann JP, Quaas A, and Arolt C
- Abstract
Introduction: Subgroups with a poorer prognosis exist among patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). This study aims to identify histological and genetic differences within HPV-positive OPSCC and correlate these findings with patient outcomes., Methods: The study included 102 OPSCC patients, all tested positive for high-risk HPV DNA and p16INK4a expression. Based on histomorphological classification (HPV Prediction Classification, HPV PC), all cases were categorized as either classic HPV-positive OPSCC (cHPV) or non-classic HPV-positive OPSCC (non-cHPV). Next-generation sequencing (NGS) of selected genes was performed on 55 tumor samples, correlating results with morphological status and survival., Results: Of all cases, 49 % (n = 50/102) were categorized as non-cHPV, histomorphologically resembling HPV-negative OPSCC, and showed significantly poorer overall survival (p = 0.004) and five-year survival rate (5YS: 83.9 % vs. 58.4 %). Multivariate analyses identified HPV PC as an independent prognostic marker (p = 0.027). NGS revealed loss-of-Function (LOF) mutations in TP53 in three non-cHPV samples. Additionally, PIK3CA/PTEN mutations were found in 35.7 % (10/28) of non-cHPV cases. The cumulative burden of gene mutations was higher in the non-cHPV subgroup compared to the cHPV subgroup (n = 53, p = 0.1)., Conclusion: HPV PC distinguished two histomorphological subgroups within HPV-positive OPSCCs: cHPV with excellent prognosis and non-cHPV with poorer overall survival. Non-cHPV tumors also exhibited higher overall mutation rates, notably LOF-TP53 and PIK3CA/PTEN mutations. These morphological subtypes, along with their corresponding mutational profiles, warrant further investigation as potential biomarkers for de-escalation intervention trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2025
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