Human Papillomavirus (HPV) infection and Erythropoietin Receptors (EPoR) expression as prognostic indicators in oropharyngeal cancer
Bibliographic record
Abstract
Background: Human papillomavirus (HPV) infection is recognized as an independent risk factor for squamous cell carcinomas (SCCs) of the head and neck, and the presence of HPV DNA is associated with a better prognosis. Recent evidence indicates a broader role for erythropoietin via binding and activation of its receptor (EpoR), which is present in many neoplastic non-hematopoietic cells. The expression of EpoR in cancer may represent a selection process that permits cancer cells to survive in an unfavorable microenvironment and may indicate aggressive cancer cell behavior. EpoR is variably expressed in head and neck cancer cells and could independently predict a poorer treatment response. Objectives: 1. To determine HPV status and the frequency of EpoR expression in archived biopsy specimens obtained from patients with oropharyngeal SCCs. 2. To evaluate whether the EpoR status affects survival and whether this putative effect is influenced by HPV status. Methods: A retrospective cohort study was conducted by reviewing the charts of 97 patients with oropharyngeal SCCs treated with primary curative intent radiation therapy at the McGill University Health Center, from 2000 to 2009. Eligible patients had to have archived tissue samples available for HPV and EpoR analysis. HPV DNA testing and typing was done using a standard polymerase chain reaction (PCR) protocol. EpoR status was determined by immunohistochemistry using rabbit polyclonal anti-EpoR staining. Stained sections were analyzed by 2 independent examiners by conventional light microscopy. A score product of 0-300 was determined for each patient by multiplying the percentage of neoplastic cells staining for EpoR (0-100%) and the intensity of the EpoR staining expressed from 0 to 3. Results: The median age was 62 years (range: 43–83). HPV status was positive in 74% of patients and this was significantly higher in patients aged ≤65 years, p=0.023. Patients with a significant smoking history (>10 pack-years) and drinking history (>4 drinks/week) were significantly more likely to be HPV negative, p= 0.041 and 0.0001 respectively. On Cox regression analysis, HPV positivity was associated with a 29% reduction in risk of death (Hazard Ratio (HR)=0.71; 95% Confidence Interval (CI): 0.34-1.49), albeit non-significantly. EpoR status was positive in 27% of patients and was associated with a non-significant 23% increase in risk of death (HR=1.23; 95%CI: 0.59-2.56). Patients who were HPV positive and EpoR negative had a non-significant 33% reduction in risk of death (HR=0.67; 95%CI: 0.29-1.56).Conclusion: This study demonstrates a trend indicating that HPV and EpoR status correlate with survival. This trend persists when patients are divided into low, intermediate and high-risk groups based on their HPV/EpoR status. The lowest risk group appears to consist of patients, which are HPV positive and EpoR negative. To the best of our knowledge this is the first study to discuss the relation of EpoR and survival in head and neck cancer.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 0.000 |
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".