p16 overexpression identifies oncogenic high‐risk HPV infection in non‐oropharyngeal squamous cell carcinoma of the head and neck

Abstract

BackgroundHuman papillomavirus (HPV) is an increasing risk factor for cancer. HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle‐related proteins, to identify HPV‐driven non‐OPSCC is less well understood.MethodsWe stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV‐status was assessed by HPV DNA PCR. In 119 non‐OPSCC, RNA in situ hybridization was additionally performed. HPV‐status was correlated with staining patterns, p53 and clinical data.ResultsThe OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV‐testing was performed in 57%, and 53% were positive for HPV DNA. HPV‐association correlated with absence of pRb and cyclin D1 and favorable outcome. In non‐OPSCC, 18% showed p16‐blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost pRb and cyclin D1. Compared to HPV‐negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV‐positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common.ConclusionsWe conclude that HPV‐positive non‐OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV‐negativity.