Torbjörn Ramqvist1, Michael Mints1, Nikolaos Tertipis1, Anders Näsman1, Mircea Romanitan2, Tina Dalianis3. 1. Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 2. Dept. of Clinical Science and Technology, Karolinska Institutet, Stockholm, Sweden; Dept. of Audiology and Neurotology, Karolinska University Hospital, Stockholm, Sweden. 3. Dept. of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: tina.dalianis@ki.se.
Abstract
OBJECTIVES: Three-year survival is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and higher (95-100%) in patients with tumors without HLA class I expression, or with high CD8(+) tumor-infiltrating lymphocyte (TIL) counts. The former paradoxical, the latter expected, but it is known that E5 and E7 can downregulate HLA class I expression. Furthermore, upon HPV integration, E2, sometimes in combination with E5 is lost. Here, HPV16 E2, E5 and E7 mRNA was therefore examined in relation to HLA class I expression, TIL counts and survival. PATIENTS AND METHODS: HPV16 DNA positive TSCC and BOTSCC biopsies, analyzed for HLA class I and CD8(+) TILs, of 133 patients, treated curatively between 2000 and 2011, were tested for HPV16 E2, E5 and E7 mRNA expression. Totally 127 samples could be evaluated and of these 117 patients, all with HPV16/E7-mRNA-positive tumors, were included in the final analysis. RESULTS: Most tumors (92%) expressed E7 mRNA, and of these 64% also expressed E2 and E5 mRNA. Patients with tumors lacking E2 mRNA had worse 3-year relapse and progression free survival (p<0.01 and p<0.05), while presence of E5 had no impact on clinical outcome. Furthermore, HLA class I expression and TILs were not correlated to E5 or to E2 mRNA expression. CONCLUSION: Lack of E2 but not E5 mRNA in HPV16 positive TSCC and BOTSCC was a negative prognostic marker. Presence of HPV16 E2, E5 and E7 mRNA expression was not correlated to HLA class I expression or CD8(+) TILs.
OBJECTIVES: Three-year survival is 80% for human papillomavirus (HPV) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and higher (95-100%) in patients with tumors without HLA class I expression, or with high CD8(+) tumor-infiltrating lymphocyte (TIL) counts. The former paradoxical, the latter expected, but it is known that E5 and E7 can downregulate HLA class I expression. Furthermore, upon HPV integration, E2, sometimes in combination with E5 is lost. Here, HPV16 E2, E5 and E7 mRNA was therefore examined in relation to HLA class I expression, TIL counts and survival. PATIENTS AND METHODS: HPV16 DNA positive TSCC and BOTSCC biopsies, analyzed for HLA class I and CD8(+) TILs, of 133 patients, treated curatively between 2000 and 2011, were tested for HPV16 E2, E5 and E7 mRNA expression. Totally 127 samples could be evaluated and of these 117 patients, all with HPV16/E7-mRNA-positive tumors, were included in the final analysis. RESULTS: Most tumors (92%) expressed E7 mRNA, and of these 64% also expressed E2 and E5 mRNA. Patients with tumors lacking E2 mRNA had worse 3-year relapse and progression free survival (p<0.01 and p<0.05), while presence of E5 had no impact on clinical outcome. Furthermore, HLA class I expression and TILs were not correlated to E5 or to E2 mRNA expression. CONCLUSION: Lack of E2 but not E5 mRNA in HPV16 positive TSCC and BOTSCC was a negative prognostic marker. Presence of HPV16 E2, E5 and E7 mRNA expression was not correlated to HLA class I expression or CD8(+) TILs.
Authors: Michael R Evans; Claire D James; Molly L Bristol; Tara J Nulton; Xu Wang; Namsimar Kaur; Elizabeth A White; Brad Windle; Iain M Morgan Journal: J Virol Date: 2019-02-05 Impact factor: 5.103
Authors: Mark Zupancic; Stefan Holzhauser; Liquin Cheng; Torbjörn Ramqvist; Juan Du; Signe Friesland; Anders Näsman; Tina Dalianis Journal: Viruses Date: 2022-05-13 Impact factor: 5.818
Authors: Yanxiao Zhang; Lada A Koneva; Shama Virani; Anna E Arthur; Alisha Virani; Pelle B Hall; Charles D Warden; Thomas E Carey; Douglas B Chepeha; Mark E Prince; Jonathan B McHugh; Gregory T Wolf; Laura S Rozek; Maureen A Sartor Journal: Clin Cancer Res Date: 2016-04-18 Impact factor: 12.531
Authors: Stefan Holzhauser; Ourania N Kostopoulou; Anna Ohmayer; Birthe K A Lange; Torbjörn Ramqvist; Teodora Andonova; Cinzia Bersani; Malin Wickström; Tina Dalianis Journal: Oncol Lett Date: 2019-10-09 Impact factor: 2.967
Authors: Michael R Evans; Claire D James; Oonagh Loughran; Tara J Nulton; Xu Wang; Molly L Bristol; Brad Windle; Iain M Morgan Journal: Oncotarget Date: 2017-06-01
Authors: Cinzia Bersani; Lars Sivars; Linnea Haeggblom; Sebastian DiLorenzo; Michael Mints; Andreas Ährlund-Richter; Nikolaos Tertipis; Eva Munck-Wikland; Anders Näsman; Torbjörn Ramqvist; Tina Dalianis Journal: Oncotarget Date: 2017-05-23