Abstract 4775: HPV16-E2/E4, -E6 and -E7 genes and HPV-disrupted human genes show large variation in expression levels in OSCC independent of the viral physical status.
Bibliographic record
Abstract
Abstract Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates to the level of viral gene transcription and influences the expression of disrupted genes. HPV16 integration sites were assessed in 75 patients with HPV16-DNA- and p16INK4A-positive OSCC using Detection of Integrated Papillomavirus Sequences (DIPS)- as well as Amplification of Papillomavirus Oncogene Transcripts (APOT)-PCR. Quantitative RT-PCR assays were carried out to determine the viral E2/E4, E6 and E7 gene expression levels. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCC. Nuclear localization of HPV16 was visualized using Fluorescence In Situ Hybridization (FISH) in 59 OSCC, and corresponding viral copy numbers were assessed by quantitative RT-PCR in 61 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we neither found significant differences in the mean expression of the viral genes E2/E4, E6 and E7, the nuclear FISH staining patters nor the viral copy numbers per cell. The expression of the HPV-invaded genes also did not significantly differ when comparing the expression in the affected tumor with the expression of that gene in either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC. Citation Format: Jens P. Klussmann, Nadine C. Olthof, Christian U. Huebbers, Jutta Kolligs, Frans CS Ramaekers, Simon Preuss, Uta Drebber, Emily Vucic, Wan Lam, Bernd Kremer, Ernst Jan Speel. HPV16-E2/E4, -E6 and -E7 genes and HPV-disrupted human genes show large variation in expression levels in OSCC independent of the viral physical status. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4775. doi:10.1158/1538-7445.AM2013-4775
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".