HPV Status as Prognostic Biomarker in Head and Neck Cancer—Which Method Fits the Best for Outcome Prediction?

Cancers

Mathias Wagner¹  Julia Caroline Radosa²  Victoria Bozzato³  Wendelin Schmid³  Florian Bochen³  Jan Philipp Kühn³  Sandrina Körner³  Alessandro Bozzato³  Bernhard Schick³  Hugo Rimbach³  Silke Wemmert³  Maximilian Linxweiler³  Luc G.T. Morris⁴  Sigrun Smola⁵ 

[1] Department of General and Surgical Pathology, Saarland University Medical Center, D-66421 Homburg, Germany;Department of Gynecology and Obstetrics, Saarland University Medical Center, D-66421 Homburg, Germany;Department of Otorhinolaryngology, Saarland University Medical Center, D-66421 Homburg, Germany;Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;Institute of Virology, Saarland University Medical Center, D-66421 Homburg, Germany;

关键词: head and neck cancer;    HPV;    prognosis;    biomarker;    p16;   

DOI  :  10.3390/cancers13184730

来源: DOAJ

【 摘 要 】

The incidence of human papillomavirus (HPV)-related head and neck cancer (HNSCC) is rising globally, presenting challenges for optimized clinical management. To date, it remains unclear which biomarker best reflects HPV-driven carcinogenesis, a process that is associated with better therapeutic response and outcome compared to tobacco/alcohol-induced cancers. Six potential HPV surrogate biomarkers were analyzed using FFPE tissue samples from 153 HNSCC patients (n = 78 oropharyngeal cancer (OPSCC), n = 35 laryngeal cancer, n = 23 hypopharyngeal cancer, n = 17 oral cavity cancer): p16, CyclinD1, pRb, dual immunohistochemical staining of p16 and Ki67, HPV-DNA-PCR, and HPV-DNA-in situ hybridization (ISH). Biomarkers were analyzed for correlation with one another, tumor subsite, and patient survival. P16-IHC alone showed the best performance for discriminating between good (high expression) vs poor outcome (low expression; p = 0.0030) in OPSCC patients. Additionally, HPV-DNA-ISH (p = 0.0039), HPV-DNA-PCR (p = 0.0113), and p16-Ki67 dual stain (p = 0.0047) were significantly associated with prognosis in uni- and multivariable analysis for oropharyngeal cancer. In the non-OPSCC group, however, none of the aforementioned surrogate markers was prognostic. Taken together, P16-IHC as a single biomarker displays the best diagnostic accuracy for prognosis stratification in OPSCC patients with a direct detection of HPV-DNA by PCR or ISH as well as p16-Ki67 dual stain as potential alternatives.

【 授权许可】

Unknown