PURPOSE: Cervical cancer is now known to be caused by infection with an oncogenic type of the human papillomavirus (HPV). However, little is known about the continued role of HPV once cancer has been established. Here, we describe the quantitative relation between HPV DNA copy number and mRNA expression of the viral oncogenes (E6 and E7) and the prognostic value of both measures in cervical cancer patients. EXPERIMENTAL DESIGN: We studied the number of viral DNA copies and the level of HPV E6/E7 mRNA expression in 75 HPV 16-positive or HPV 18-positive International Federation of Gynecology and Obstetrics stage Ib and IIa cervical cancer patients. Measurements were done with quantitative PCR. DNA copy number analysis was done on pure tumor cell samples enriched with flow sorting. mRNA expression data were compensated for the percentage of tumor cells included. RESULTS: The number of viral DNA copies was not predictive of survival in cervical cancer patients. In contrast, high HPV E6/E7 mRNA expression was strongly related to an unfavorable prognosis (P = 0.006). In a multivariate Cox model for overall survival, including all known prognostic variables and stratified for HPV type, the level of E6/E7 mRNA expression was an independent prognostic indicator, second only to lymph node status. No correlation was observed between DNA copy number and the level of HPV E6/E7 mRNA expression, which reflects that not all DNA copies are equally transcriptionally active. CONCLUSIONS: Cervical cancer patients with high HPV E6/E7 oncogene mRNA expression have a worse survival independently from established prognostic factors.
PURPOSE:Cervical cancer is now known to be caused by infection with an oncogenic type of the human papillomavirus (HPV). However, little is known about the continued role of HPV once cancer has been established. Here, we describe the quantitative relation between HPV DNA copy number and mRNA expression of the viral oncogenes (E6 and E7) and the prognostic value of both measures in cervical cancerpatients. EXPERIMENTAL DESIGN: We studied the number of viral DNA copies and the level of HPV E6/E7 mRNA expression in 75 HPV 16-positive or HPV 18-positive International Federation of Gynecology and Obstetrics stage Ib and IIa cervical cancerpatients. Measurements were done with quantitative PCR. DNA copy number analysis was done on pure tumor cell samples enriched with flow sorting. mRNA expression data were compensated for the percentage of tumor cells included. RESULTS: The number of viral DNA copies was not predictive of survival in cervical cancerpatients. In contrast, high HPV E6/E7 mRNA expression was strongly related to an unfavorable prognosis (P = 0.006). In a multivariate Cox model for overall survival, including all known prognostic variables and stratified for HPV type, the level of E6/E7 mRNA expression was an independent prognostic indicator, second only to lymph node status. No correlation was observed between DNA copy number and the level of HPV E6/E7 mRNA expression, which reflects that not all DNA copies are equally transcriptionally active. CONCLUSIONS:Cervical cancerpatients with high HPV E6/E7 oncogene mRNA expression have a worse survival independently from established prognostic factors.
Authors: Tingting Qin; Lada A Koneva; Yidan Liu; Yanxiao Zhang; Anna E Arthur; Katie R Zarins; Thomas E Carey; Douglas Chepeha; Gregory T Wolf; Laura S Rozek; Maureen A Sartor Journal: Head Neck Date: 2020-05-14 Impact factor: 3.147
Authors: David Lindquist; Mircea Romanitan; Lalle Hammarstedt; Anders Näsman; Hanna Dahlstrand; Johan Lindholm; Liselotte Onelöv; Torbjörn Ramqvist; Weimin Ye; Eva Munck-Wikland; Tina Dalianis Journal: Mol Oncol Date: 2007-09-01 Impact factor: 6.603
Authors: Nadine C Olthof; Christian U Huebbers; Jutta Kolligs; Mieke Henfling; Frans C S Ramaekers; Iris Cornet; Josefa A van Lent-Albrechts; Alexander P A Stegmann; Steffi Silling; Ulrike Wieland; Thomas E Carey; Heather M Walline; Susanne M Gollin; Thomas K Hoffmann; Johan de Winter; Bernd Kremer; Jens P Klussmann; Ernst-Jan M Speel Journal: Int J Cancer Date: 2014-08-14 Impact factor: 7.396