cad a22 4500 551468343 20190216043544.0 cr unu---uuuuu 181215e201808 xx s 000 0 eng 10.5167/uzh-159449 doi 10.1002/lio2.175 doi (ZORA)oai:www.zora.uzh.ch:159449 610 ddc 30186959 pmid Comparison of PI3K Pathway in HPV-Associated Oropharyngeal Cancer With and Without Tobacco Exposure [Elektronische Daten] [Si-Young Kiessling, Martina Anja Broglie, Alex Soltermann, Gerhard Frank Huber, Sandro Johannes Stoeckli] openAccess eu-repo Objectives The aim of the study was to evaluate whether HPV associated OPSCC with tobacco exposure follows a different carcinogenic pathway compared to HPV associated OPSCC without tobacco exposure and to investigate its prognostic significance. The question was addressed with focus on components of the PI3K pathway. Methods 184 patients with newly diagnosed OPSCC treated with curative intent were consecutively enrolled. The expression level of p16, p53, PI3K, mTOR, and PTEN was assessed by immunohistochemistry and analyzed in relation to the risk factors HPV status and tobacco exposure. Results 94 of 184 (51%) patients were p16 positive, p53 overexpression was detected in 48 of 184 (26%) cases. PI3K overexpression with 70 of 184 (38%) cases was significantly higher in p16 positive tumors. mTOR overexpression was present in 90 of 184 (49%) cases and significantly higher in p16 negative tumors. PTEN loss was found in 42 of 184 (23%) cases without association to p16 expression. p16 positive OPSCC showed lower rates of p53 expression and mTOR expression as well as higher rates of PI3K expression irrespective of tobacco exposure. Survival analysis showed a distinct intermediate survival rate of p16 positive smokers. The markers PI3K, mTOR, and PTEN did not have a significant impact on survival. Conclusion HPV associated OPSCC with tobacco exposure follows the same expression level of the PI3K pathway as HPV associated OPSCC without tobacco exposure. The impaired survival rate of the intermediate risk group cannot be explained by different expression patterns of PI3K, mTOR, and PTEN. Level of Evidence 2b. Clinic for Otorhinolaryngology zora Institute of Pathology and Molecular Pathology zora Kiessling Si-Young joint author Broglie Martina Anja joint author Soltermann Alex joint author Huber Gerhard Frank joint author Stoeckli Sandro Johannes joint author Laryngoscope Investigative Otolaryngology 3(4):283-289 https://www.zora.uzh.ch/id/eprint/159449/1/Kiessling_laryngoscope_investigative_otolaryngology_2018.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/159449/1/Kiessling_laryngoscope_investigative_otolaryngology_2018.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Kiessling Si-Young joint author ZORA 700 1- Broglie Martina Anja joint author ZORA 700 1- Soltermann Alex joint author ZORA 700 1- Huber Gerhard Frank joint author ZORA 700 1- Stoeckli Sandro Johannes joint author ZORA 773 0- Laryngoscope Investigative Otolaryngology 3(4):283-289 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess