Nikolaos Tertipis1, Ulf Hammar2, Anders Näsman1, Andrea Vlastos3, Cecilia Nordfors1, Nathalie Grün1, Andreas Ährlund-Richter1, Lars Sivars1, Linnea Haeggblom1, Linda Marklund4, Lalle Hammarstedt-Nordenvall4, Anil K Chaturvedi5, Eva Munck-Wikland4, Torbjörn Ramqvist1, Matteo Bottai2, Tina Dalianis6. 1. Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 2. Dept. of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 3. 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. 4. Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital, Stockholm, Sweden. 5. Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. 6. Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: tina.dalianis@ki.se.
Abstract
AIM: 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. PATIENTS AND 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). CONCLUSION: 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.
AIM: 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. PATIENTS AND 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). CONCLUSION: 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: Lars Sivars; Cinzia Bersani; Nathalie Grün; Torbjörn Ramqvist; Eva Munck-Wikland; Christian Von Buchwald; Tina Dalianis Journal: Mol Clin Oncol Date: 2016-10-13
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