title: A proportion of primary squamous cell carcinomas of the parotid gland harbour high-risk human papillomavirus.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Bin
authors.identifier: http://orcid.org/0000-0003-4638-9835
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Borsu
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Ghossein
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Katabi
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Ganly
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Dogan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications*; D010307:Parotid Neoplasms / Q000235:genetics* / Q000821:virology*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor
keywords: human papillomavirus; in-situ hybridization; p16; parotid gland; squamous cell carcinoma