Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region

Steffen Wagner; Christine Langer; Nora Wuerdemann; Susanne Reiser; Helen Abing; Jörn Pons-Kühnemann; Elena-Sophie Prigge; Magnus von Knebel Doeberitz; Stefan Gattenlöhner; Tim Waterboer; Lea Schroeder; Christoph Arens; Jens Peter Klussmann; Claus Wittekindt

doi:10.3390/cancers15072167

Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region

Cancers (Basel). 2023 Apr 6;15(7):2167. doi: 10.3390/cancers15072167.

Authors

Steffen Wagner¹, Christine Langer¹, Nora Wuerdemann^{1

2}, Susanne Reiser¹, Helen Abing², Jörn Pons-Kühnemann³, Elena-Sophie Prigge^{4

5}, Magnus von Knebel Doeberitz^{4

5}, Stefan Gattenlöhner⁶, Tim Waterboer⁷, Lea Schroeder⁷, Christoph Arens¹, Jens Peter Klussmann^{1

2}, Claus Wittekindt^{1

8}

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Giessen, 35392 Giessen, Germany.
² Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, 50937 Cologne, Germany.
³ Medical Statistics, Institute of Medical Informatics, University of Giessen, 35392 Giessen, Germany.
⁴ Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
⁵ Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁶ Institute of Pathology, University of Giessen, 35392 Giessen, Germany.
⁷ Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
⁸ Department of Otorhinolaryngology, Klinikum Dortmund gGmbH, University Hospital Witten/Herdecke, 44137 Dortmund, Germany.

Abstract

Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUP_HNSCC), much less is known.

Methods: We assessed a consecutive cohort of CUP_HNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16^INK4a (p16) expression, and risk factors to identify prognostic classification markers.

Results: In 32/103 (31%) CUP_HNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUP_HNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption.

Conclusions: Despite obvious differences, CUP_HNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUP_HNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.

Keywords: carcinoma of unknown primary (CUP); head and neck cancer; human papillomavirus (HPV); oropharyngeal squamous cell carcinomas (OPSCC); principal component analysis; risk model.

Grants and funding

This research received no external funding.