A proportion of primary squamous cell carcinomas of the parotid gland harbour high‐risk human papillomavirus

AIMS: In the current study, we aimed to examine primary parotid squamous cell carcinoma (ParSCC) for the presence of high-risk human papillomavirus (HR-HPV) and associated molecular alterations. METHODS AND RESULTS: Eight cases of ParSCC were retrieved after a detailed clinicopathological review to exclude the possibility of metastasis and/or extension from another primary site. HR-HPV status was determined on the basis of immunohistochemistry (IHC) for p16 expression and chromogenic in-situ hybridization (CISH) for HR-HPV. All cases were genotyped with a multiplexed mass spectrometry assay interrogating 91 hotspot mutations in eight cancer-related genes (EGFR, KRAS, NRAS, BRAF, PIK3CA, AKT1, MEK1 and ERBB2), and studied by fluorescence in-situ hybridization for PTEN copy number alteration. Three of eight cases (37.5%) were positive for the presence of HR-HPV by CISH and p16 IHC. One of three (33%) HR-HPV-positive cases harboured a PTEN hemizygous deletion, and one (33%) HR-HPV-positive case harboured a PIK3CA E545K somatic mutation. No alteration of the PTEN-PI3K pathway was detected in HR-HPV-negative tumours. Over a median follow-up period of 66.2 months, only the patient with the HR-HPV-positive PIK3CA-mutated tumour died of his disease, the remaining seven patients being disease-free. CONCLUSIONS: Given the established aetiological role of HR-HPV in other head and neck squamous cell carcinomas, it is likely that HR-HPV represents an oncogenic driver in the pathogenesis of more than one-third of ParSCCs. The presence of HR-HPV in ParSCC may be coupled with alterations in the PTEN-PI3K pathway. Further studies on HR-HPV and the molecular characterization of a larger number of ParSCCs are needed to determine the clinical significance of these findings.