| Abstract: |
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 un-clear 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 corre-lation 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 multi-variable analysis for oropharyngeal cancer. In the non‐OPSCC group, however, none of the afore-mentioned surrogate markers was prognostic. Taken together, P16‐IHC as a single biomarker dis-plays 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
