Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8 + Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

• Published in: Anticancer research 2017-02, Vol.37 (2), p.665-674
• Main Authors: Sivars, Lars, Landin, David, Grün, Nathalie, Vlastos, Andrea, Marklund, Linda, Nordemar, Sushma, Ramqvist, Torbjörn, Munck-Wikland, Eva, Näsman, Anders, Dalianis, Tina
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers, Tumor - immunology; CD8-Positive T-Lymphocytes - immunology; Cyclin-Dependent Kinase Inhibitor p16 - immunology; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA, Viral - genetics; DNA, Viral - immunology; Female; Head and Neck Neoplasms - diagnosis; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - virology; Host-Pathogen Interactions - immunology; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medicin och hälsovetenskap; Middle Aged; Multivariate Analysis; Neoplasms, Unknown Primary - diagnosis; Neoplasms, Unknown Primary - immunology; Neoplasms, Unknown Primary - virology; Papillomaviridae - genetics; Papillomaviridae - immunology; Papillomaviridae - physiology; Papillomavirus Infections - immunology; Papillomavirus Infections - virology; Polymerase Chain Reaction; Prognosis; Sensitivity and Specificity
• ISSN: 0250-7005; 1791-7530; 1791-7530
• DOI: 10.21873/anticanres.11362

Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPV-negative HNCUP. However, not all studies concord. Here, our previous finding was investigated in a new cohort and additional biomarkers were analyzed. A total of 19 HNCUPs diagnosed 2008-2013 were analyzed for HPV DNA by polymerase chain reaction assay (PCR) and p16 by immunohistochemistry (IHC). Thereafter, 69 HNCUPs diagnosed between 2000-2013 were analyzed for HPV16 mRNA by PCR (if HPV16DNA-positive) and cluster of differentiation 8 positive (CD8 ) tumour-infiltrating lymphocytes (TILs) and human leukocyte antigen (HLA) class I-expression using IHC. HPV DNA, alone and in combination with p16 overexpression, was validated as a favourable prognostic factor in HNCUP. HPV16 mRNA was present in most HPV16 DNA-positive cases, confirming HPV-driven carcinogenesis in HNCUP. High CD8 TIL counts indicated favourable prognosis. HPV status is useful for the management of patients with HNCUP and the role of CD8 TILs should be further explored.