title: A model for predicting clinical outcome in patients with human papillomavirus-positive tonsillar and base of tongue cancer.
abstract: OBJECTIVE
  To combine clinical and molecular markers into an algorithm for predicting outcome for individual patients with human papillomavirus (HPV) DNA/p16(INK4a) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC).
  
  
  BACKGROUND
  Head-neck cancer treatment has become more intensified, comprising not only surgery and radiotherapy, but also induction/concomitant chemotherapy and targeted therapy. With less treatment, 3-year disease free survival (DFS) is 80% for HPV-positive TSCC and BOTSCC. An 85-100% 3-year DFS is observed for HPV(+) TSCC and BOTSCC with absence of HLA class I, or CD44 expression, or high CD8(+) tumour-infiltrating lymphocyte (TIL) counts suggesting that therapy could be tapered for many if patients could be identified individually.
  
  
  METHODS
  Patients treated curatively, with HPV DNA/p16(INK4a) positive tumours examined for HLA class I and II, CD44 and CD8(+)TILs, were included. An L1-regularised logistic regression was used to evaluate the effect of the biomarker data, age, stage, diagnosis, smoking and treatment on 3-year risk of death or relapse on a training cohort of 197 patients diagnosed 2000-2007 and validated on a cohort of 118 patients diagnosed 2008-2011.
  
  
  RESULTS
  The variables finally included in the model were HLA class I, CD8(+) TILs, age, stage and diagnosis (TSCC or BOTSCC). The model showed acceptable discrimination and calibration. The discriminative ability of the model did not diminish after validation (AUC=0.77).
  
  
  CONCLUSIONS
  To our knowledge, this is the first model to utilise information from several markers to predict an individual probability of clinical outcome for patients with HPV DNA/p16(INK4a) positive tumours.
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tertipis
authors.affiliation: Dept. of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hammar
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Näsman
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vlastos
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nordfors
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grün
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ährlund-Richter
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Sivars
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Linnea
authors.initials: L
authors.lastname: Haeggblom
authors.affiliation: Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Marklund
authors.affiliation: Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lalle
authors.initials: L
authors.lastname: Hammarstedt-Nordenvall
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
authors.affiliation: Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
authors.affiliation: Dept. of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: tina.dalianis@ki.se.
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000821:virology; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D014062:Tongue Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014067:Tonsillar Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D018960:Hyaluronan Receptors
keywords: Base of tongue cancer; Biomarkers; HPV; Survival; Tonsillar cancer