HPV-independent CIN-lesions of the uterine cervix – a new concept
Bibliographic record
Abstract
Purpose : There is increasing evidence about HPV-independent (HPVI) squamous cell carcinomas of the uterine cervix (CSCC). While HPV-associated CSCC precursor lesions (i.e. high-grade squamous intraepithelial lesion, HSIL) are well characterised, features of HPVI-precursors are limited. Methods : Histopathological and immunohistochemical evaluation (p16, p53) as well as mutational analysis by next generation sequencing performed on HPV high-risk DNA negative (HPVI) squamous precursor lesions. Results : Six cases were available with a mean age of 74.5 years of age (range 64 to 83 years). Five precursors represented dVIN-like morphology, associated with aberrant p53-immunoepression (parabasal/diffuse overexpression), non-block-like p16 staining and pathogenic TP53-mutation, seen in patients with uterine prolaps. One case not associated with prolapsed uterus represented features similar to HPV-associated HSIL, no p16-overexpression but p53-wildtype staining pattern. On molecular level pathogentic TERT promotor mutation and a possible pathogenic mutation of HRAS occurred. Conclusion : HPVI squamous precursor lesion of the uterine cervix are exceedingly rare and represent a range of morphologic findings. Some lesions represent features seen in differentiated vulvar intraepithelial neoplasia (dVIN-like) and others features similar to HPV high-risk associated HSIL. Molecular alterations are variable with TP53-mutation (dVIN-like HPVI precursors) and TERT- as well as HRAS-alteration (HSIL-like HPVI precursor). Publication History Article published online: 11 June 2025 © . Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.001 |
| Science and technology studies | 0.001 | 0.009 |
| Scholarly communication | 0.004 | 0.009 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.002 | 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".