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• W4253895337 abstract "Integration of HPV-DNA is a major step for the oncogenic progression in epithelial cells, but in a subgroup of patients with cervical cancer the virus-DNA is still episomal, which leads to an intact viral E2-gene, a regulator of the viral oncogenes E6 and E7. Disruption of the E2-gene is a consequence of integration of the virus into its host DNA. This study was performed to investigate the influence of episomal DNA on phenotype and outcome in patients with advanced cervical cancer treated with primary radiotherapy. Paraffin embedded biopsies of 82 women with locally advanced cervical cancer could be analysed for HPV infection and E2 gene integrity by multiplex PCR (SP1/2). For negative samples PCR was repeated using GP5/6 primer to exclude false negative PCR-results due to a loss of the L1 region covered by SP1/2 primers. Statistical analyses (Kaplan-Meier method; log-rank test) were performed for overall survival (OS), disease free survival (DFS), local progression free survival (LPFS), and distant metastases free survival (DMFS). Tested parameters were: HPV-status and type, E2-gene status, p53 expression, grade, hemoglobin level, nodal status, age, FIGO stage, RT dose, and histology. Sixty-one (75 %) of 82 carcinomas were HPV positive: 44 HPV16 (72 %), 8 HPV 33 (13 %), 2 HPV 31, 1 HPV 6, 13, 18 and 58. Two types could not be specified. Twenty-one samples were HPV-negative. Seventeen out of 44 HPV-16 positive tumors (39 %) had an intact E2-gene. Overall, there was no difference in outcome between HPV-negative and HPV-positive tumors. Patients with an HPV-positive tumor with intact E2-gene (E2-positive) showed a better DFS (Figure 1) and a trend for a better OS and DMFS compared to the group with an integrated virus (E2-negative) (3-yrs: 58 % vs. 38 %, p = 0.06; 87 % vs. 66 %, p = 0.1; and 57 % vs. 48 %, p = 0.1). LPFS for both groups was not statistically different (3-yrs: 74 % vs. 60 %, p = 0.55). There was no survival difference between HPV 16-positive tumors with an integrated virus and HPV-negative tumors. The only significant parameter for all endpoints was nodal status. Tumors with an intact E2-gene might represent a less aggressive disease. This could be caused by suppressing viral oncogenes E6 and E7." @default.
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• W4253895337 date "2004-09-01" @default.
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• W4253895337 title "The impact of human papillomavirus (HPV) infection and E2-gene integrity on outcome in cervical cancer: A possibility for individualizing therapy" @default.
• W4253895337 doi "https://doi.org/10.1016/s0360-3016(04)01532-9" @default.
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