Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma

Malte Suchan¹, Nora Wuerdemann², Steffen Wagner³, Christine Langer³, Christoph Arens³, Jannik Johannsen⁴, Johanna Prinz⁵, Shachi Jenny Sharma⁴, Arthur Charpentier⁴, Marcel Mayer⁴, Charlotte Klasen⁴, Philipp Zimmermann⁴, Hans Eckel⁴, Christopher Kopp⁴, Christian U Huebbers⁶, Sebastian Klein⁷, Janna Siemanowski⁸, Jörn Meinel⁸, Jens Peter Klussmann⁹, Alexander Quaas⁸, Christoph Arolt⁸

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany. Electronic address: malte.suchan@uk-koeln.de.
² Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
³ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Giessen, Giessen, Germany.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany.
⁵ Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University of Cologne, Cologne, Germany.
⁷ Department of Hematology and Stem Cell Transplantation, University Duisburg-Essen, University Hospital Essen, Essen, Germany.
⁸ Institute of Pathology, University of Cologne, Medical Faculty, Cologne, Germany.
⁹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.

PMID: 39893876
DOI: 10.1016/j.oraloncology.2025.107209

Free article

Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma

Malte Suchan et al. Oral Oncol. 2025 Mar.

Free article

. 2025 Mar:162:107209.

doi: 10.1016/j.oraloncology.2025.107209. Epub 2025 Feb 1.

Authors

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany. Electronic address: malte.suchan@uk-koeln.de.
² Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
³ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Giessen, Giessen, Germany.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany.
⁵ Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
⁶ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Molecular Head and Neck Oncology, Translational Research in Infectious Diseases and Oncology (TRIO) Research Building, University of Cologne, Cologne, Germany.
⁷ Department of Hematology and Stem Cell Transplantation, University Duisburg-Essen, University Hospital Essen, Essen, Germany.
⁸ Institute of Pathology, University of Cologne, Medical Faculty, Cologne, Germany.
⁹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Medical Faculty, University of Cologne, Cologne, Germany; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.

PMID: 39893876
DOI: 10.1016/j.oraloncology.2025.107209

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.

Keywords: Genetic alterations; Histomorphology; Human papillomavirus (HPV); Oropharyngeal squamous cell carcinoma (OPSCC); Prognosis; Survival.

PubMed Disclaimer

Conflict of interest statement

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.

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma

Affiliations

Histological and genetic criteria define a clinically relevant subgroup of HPV-positive oropharyngeal carcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous