title: HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.
abstract: HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Näsman
authors.forename: Emilia
authors.initials: E
authors.lastname: Andersson
authors.forename: Linda
authors.initials: L
authors.lastname: Marklund
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tertipis
authors.forename: Lalle
authors.initials: L
authors.lastname: Hammarstedt-Nordenvall
authors.forename: Per
authors.initials: P
authors.lastname: Attner
authors.forename: Tommy
authors.initials: T
authors.lastname: Nyberg
authors.forename: Giuseppe V
authors.initials: GV
authors.lastname: Masucci
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II