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

Abstract

Aims In the current study, we aimed to examine primary parotid squamous cell carcinoma (ParSCC) for the presence of HR-HPV and associated molecular alterations. Methods and results Eight cases of ParSCC were retrieved after a detailed clinicopathologic review to exclude a possibility of metastasis and/or extension from another primary site. HR-HPV status was determined based on immunohistochemistry (IHC) for p16 protein expression and by chromogenic in situ hybridization (CISH) for HR-HPV. All cases were genotyped by multiplexed mass spectrometry assay interrogating 91 hotspot mutations in 8 cancer-related genes (EGFR, KRAS, NRAS, BRAF, PIK3CA, AKT1, MEK1 and ERBB2), and studied by fluorescence in situ hybridization (FISH) for PTEN copy number alteration. Three of 8 cases (37.5%) were positive for presence of HR-HPV by CISH and p16 IHC. One of three (33%) HR-HPV-positive cases harbored PTEN hemizygous deletion, and one (33%) HR-HPV-positive case harbored PIK3CA E545K somatic mutation. No alteration of PTEN-PI3K pathway was detected in HR-HPV-negative tumors. Over a median follow-up period of 66.2 months, only the patient with HR-HPV-positive PIK3CA-mutated tumor died of his disease, while the remaining 7 patients were disease free. Conclusions Given the established etiologic role of HR-HPV in other head and neck squamous cell carcinoma, it is likely that HR-HPV represents an oncogenic driver in the pathogenesis of more than one third of ParSCC. Presence of HR-HPV in ParSCC may be coupled with alterations in PTEN-PI3K pathway. HR-HPV and molecular characterization of a larger number of ParSCC is needed to determine the clinical significance of these findings.

No evidence for human papillomavirus having a causal role in salivary gland tumors

“…a viral infection may be the causative factor. There are a handful small studies that have shown an association between HPV infection and certain salivary gland malignancies, however, reported HPV prevalence varied to a great extent, as summarized in Additional file 1 : Table S1 [ 10 – 17 ]. Moreover, these studies included only a small sample size, and most studies only included one or few specific subtypes of salivary gland tumors with very few samples in each subgroup, thus missing proper control groups.…”

Prognostic relevance of epithelial–mesenchymal transition and proliferation in surgically treated primary parotid gland cancer

“…This becomes of interest when therapy planning is influenced by histopathological entity and when estimated clinical course and aggressiveness of the tumour subtypes determine therapy extent. Despite the success of finding tumour features that allow reliable prognostic estimation in other human carcinomas in recent years (eg, hormone receptor status in breast cancer,11 Human papillomavirus (HPV) status in oral squamous cell carcinoma (OSCC))12, the only prognostic features of PGC remain the tumours' TNM status, grading, patients' age and success of primary therapy 13–15. Identification of validated biomarkers might contribute to a more accurate risk and prognostic estimation for individual cases leading to personalised therapy concepts and prevention of overtreatment or undertreatment.…”

Primary squamous cell carcinoma of the salivary gland: immunohistochemical analysis and comparison with metastatic squamous cell carcinoma

“…Wolff et al [ 10 ] studied c-erbB2 expression in salivary gland carcinoma according to histologic subtype and aggressive behavior. Considering previous results, this study intended to determine the expressional characteristics in primary SCC and metastatic SCC [ 10 - 12 ]. Although the pathogenesis of primary SCC of the salivary gland is unknown, it can be associated with squamous metaplasia of the salivary duct or previous radiation treatment [ 4 , 5 ].…”