BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) represents a distinct tumour entity in comparison to HPV-negative OPSCC. The clinical, radiological, morphological features and distribution of HPV E6/E7 mRNA were investigated in resected specimens of OPSCC.

METHODS: We retrieved formalin-fixed, paraffin-embedded whole section slides from 24 p16/HPV-DNA positive and 18 p16/HPV-DNA negative primary tumours and 16 corresponding metastases in patients with early-stage OPSCC who underwent planned curative or diagnostic primary transoral robotic surgery. A detailed clinicoradiological and histopathological investigation of the tumours was performed along with detection of HPV E6/E7 mRNA by in situ hybridisation.

RESULTS: HPV-driven OPSCC was characterised by non-keratinising morphology and was dominated by a cohesive invasion pattern at the leading edge of the tumour. Dysplastic zones of the squamous epithelium were strictly located in the tonsillar crypts in contrast to HPV-negative OPSCC which predominantly arised from the dysplastic surface epithelium. Thirteen HPV-driven OPSCC invaded through the tonsillar lymphoid compartment and into soft tissue, causing a stromal desmoplastic reaction. HPV mRNA was consistently but inhomogenously expressed in the entire tumour area and in the dysplastic squamous epithelium. There was no HPV expression in the adjacent normal epithelium and in the non-neoplastic tissues.

CONCLUSIONS: This study enhances the current understanding of HPV-driven OPSCC. Only tumours that invade through the lymphoid compartment induce a stromal desmoplastic reaction. A consistent but inhomogenous expression of E6 and E7 mRNA was found in tumour and dysplastic areas, emphasizing that the E6/E7 oncogenes are the driving factors in HPV-driven OPSCC.