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.
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.
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden Lars.Sivars@ki.se Tina.Dalianis@ki.se.
Lars
L
Sivars
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
David
D
Landin
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Nathalie
N
Grün
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
Andrea
A
Vlastos
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
Linda
L
Marklund
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
Sushma
S
Nordemar
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
Torbjörn
T
Ramqvist
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden.
Eva
E
Munck-Wikland
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.|Department of Clinical Pathology, Karolinska University Hospital, Stockholm, Sweden.
Anders
A
Näsman
Department of Clinical Science, Intervention and Technology, Division of ENT Diseases, Karolinska Institute, Stockholm, Sweden Lars.Sivars@ki.se Tina.Dalianis@ki.se.
Tina
T
Dalianis
D000368:Aged; D014408:Biomarkers, Tumor / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000276:immunology / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009382:Neoplasms, Unknown Primary / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000502:physiology; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral
Human papillomavirus; head and neck cancer; lymphocytes; neoplasms; oropharyngeal cancer; tumor-infiltrating; unknown primary