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

• Main Authors: Jan Philipp Kühn, Wendelin Schmid, Sandrina Körner, Florian Bochen, Silke Wemmert, Hugo Rimbach, Sigrun Smola, Julia Caroline Radosa, Mathias Wagner, Luc G.T. Morris, Victoria Bozzato, Alessandro Bozzato, Bernhard Schick, Maximilian Linxweiler
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Cancers
• Subjects: head and neck cancer; HPV; prognosis; biomarker; p16
• Online Access: https://www.mdpi.com/2072-6694/13/18/4730

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 (<i>n</i> = 78 oropharyngeal cancer (OPSCC), <i>n</i> = 35 laryngeal cancer, <i>n</i> = 23 hypopharyngeal cancer, <i>n</i> = 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; <i>p</i> = 0.0030) in OPSCC patients. Additionally, HPV-DNA-ISH (<i>p</i> = 0.0039), HPV-DNA-PCR (<i>p</i> = 0.0113), and p16-Ki67 dual stain (<i>p</i> = 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.