Human Papillomavirus DNA and E6/E7 mRNA Status in Relation to Survival of Patients Treated for Cervical Squamous Cell Carcinoma



Ruth Holm*, 1, Irene Kraus2, 3, Hanne Skomedal3, Anita Langerød4, Gunnar B Kristensen5, 6, Heidi Lyng7
1 Division of Pathology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
2 Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway
3 NorChip AS, Klokkarstua, Norway
4 Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
5 Department of Gynaecologic Oncology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
6 Department of Medical Informatics, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway
7 Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Oslo, Norway


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© Holm et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Division of Pathology, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway; Tel: (47) 22934207; Fax: (47) 22730164; E-mail: ruth.holm@radiumhospitalet.no


Abstract

The prognostic significance of human papillomavirus (HPV) DNA and E6/E7 mRNA, the presence of specific types, and the physical state of HPV DNA, were studied in 202 cervical squamous cell carcinomas. Absence or non-detectable levels of high-risk (types 16, 18, 31, 33, 35, 45, 52 and 58) E6/E7 mRNA, using the real-time nucleic acid sequence based amplification (NASBA) assay, and absence of HPV high-risk/HPV 6, 26, 66, 69, 73 (all methods collectively) were associated with poor overall survival in univariate analysis (P = 0.04 and P = 0.03, respectively) and had independent prognostic value in multivariate analysis (P = 0.01 and P = 0.03, respectively) including FIGO stage and age. Based on the individual results of type-specific PCR and in situ hybridization (ISH), the presence of HPV DNA was not found to be a prognostic factor. Likewise, concerning the presence of specific HPV types and the HPV integration status (determined by ISH), no prognostic significance was found. Mutation analyses of the TP53 gene revealed mutations in 3 of the 6 HPV negative samples (50%).