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

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RESEARCH

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No evidence for human papillomavirus having a causal role in salivary gland tumors Linnea Haeggblom1*†, Ramona Gabriela Ursu2†, Leila Mirzaie1, Tove Attoff1, Caroline Gahm3,4, Lalle Hammarstedt Nordenvall3,4 and Anders Näsman1,5

Abstract Background: Salivary gland malignancies are a very heterogeneous group of cancers, with histologically > 20 different subtypes, and prognosis varies greatly. Their etiology is unknown, however, a few small studies show presence of human papillomavirus (HPV) in some subtypes, although the evidence for HPV having a causal role is weak. The aim of this study was to investigate if HPV plays a causal role in the development of different parotid salivary gland tumor subtypes. Methods: DNA was extracted from 107 parotid salivary gland formalin fixed paraffin embedded tumors and 10 corresponding metastases, and tested for 27 different HPV types using a multiplex bead based assay. HPV DNA positive tumors were stained for p16INK4a overexpression by immunohistochemistry. Results: One of the 107 malignant parotid salivary gland tumors (0.93%) and its corresponding metastasis on the neck were positive for HPV16 DNA, and both also overexpressed p16INK4a. The HPV positive primary tumor was a squamous cell carcinoma; neither mucoepidermoid nor adenoid cystic tumors were found HPV positive. Conclusions: In conclusion, HPV DNA analysis in a large number of malignant parotid salivary gland tumors, including 12 different subtypes, did not show any strong indications that tested HPV types have a causal role in the studied salivary gland tumor types. Keywords: Salivary gland tumors, Salivary gland malignancies, Human papilloma virus, HPV, Tumor viruses

Background Salivary gland malignancies are a very heterogeneous group of cancers, where histologically more than 20 different subtypes have been identified and prognosis varies greatly [1]. These tumors are rare, yet affect patients in all age groups and are mainly found in the parotid gland, but can also be found in submandibular, sublingual and accessory parotid glands [2, 3]. In Sweden about 100 new cases of salivary gland cancers are diagnosed each year, accounting for about 8% of head and neck cancers [3], which is similar to 6% of head and neck cancers in the United States [2]. Today the determination of tumor subtype is mainly based on the pathologist’s histological evaluation, and due to the large histological variability in * Correspondence: [email protected] † Linnea Haeggblom and Ramona Gabriela Ursu contributed equally to this work. 1 Department of Oncology-Pathology, Karolinska Institute, Cancer Center Karolinska, R8:01, Karolinska University Hospital, 171 76 Stockholm, Sweden Full list of author information is available at the end of the article

this group of tumors, diagnoses are often determined with uncertainty. As a supportive measure genetic profiling is used in some cases, however, the sensitivity of the tests varies greatly. Moreover, it may often be with great uncertainty the prognostic tumor grade is d