Abstract 4663: Human papillomavirus circulating tumor DNA for risk stratification in cervical cancer
Notice bibliographique
Résumé
Background: Human papillomavirus (HPV) DNA is detectable in the peripheral blood plasma from patients with locally advanced and metastatic cervical cancer. Levels of HPV circulating tumor DNA (ctDNA) in pretreatment plasma have weak associations with prognosis, but the significance of detecting HPV integration into the host genome or fragmentation features within HPV ctDNA has not been explored. We hypothesized that these molecular features of HPV ctDNA may serve as prognostic biomarkers and reflect HPV biology, independent from total ctDNA abundance. Methods: Plasma cell-free DNA was collected at baseline from 57 patients with locally advanced cervical cancer (stage IB-IVA) and 21 patients with metastatic cervical cancer. Whole viral genome sequencing was performed following hybrid capture. HPV ctDNA levels were expressed in copies/mL plasma. HPV integration sites were detected using SearcHPV. Progression-free survival (PFS) was evaluated using Kaplan-Meier analysis and log-rank tests. The normalized fragment midpoint coverage across the HPV-16 genome was calculated for individual samples and averaged across patient groups. NuPoP, was used to calculate the expected nucleosome occupancy at each base pair of the HPV-16 genome. Peaks corresponding to the observed nucleosome occupancy within our cohorts were called using pracma, and occupancy probabilities were calculated for each peak. Results: Baseline HPV ctDNA levels were detected in 57/57 locally advanced patients (median=283 copies/mL) and 20/21 metastatic patients (median=299 copies/mL). Unique HPV integration sites were detected at varying levels in 21/57 locally advanced patients (median sites:1, range:0-23) and 12/21 metastatic patients (median sites:2, range:0-45) (Wilcoxon p=0.8). No significant differences in PFS were observed in locally advanced or metastatic patients when stratified by median ctDNA levels (p=0.7 and p=0.8 respectively). However, high confidence integration detected at baseline was associated with inferior PFS in locally advanced patients (p=0.01), but not metastatic (p=0.28). HPV ctDNA fragment coverage varied across the HPV-16 genome with the number of observed merged peaks being 32 in the locally advanced cohort (n=36) and 31 in the metastatic cohort (n=14). The median expected nucleosome occupancy probabilities across all peaks were 98.6% and 97.2%, respectively. Conclusion: Detection of viral integration within baseline HPV ctDNA was associated with significantly inferior PFS in locally advanced patients. Peaks in the average HPV-16 ctDNA coverage profiles corresponded to high expected nucleosome occupancy in both the locally advanced and metastatic cohorts, suggesting that ctDNA may reflect chromatin accessibility of the virus. These findings suggest that quantitative and qualitative features of HPV ctDNA from baseline plasma may reflect HPV biology associated with cervical cancer. Citation Format: Emma M. Collier, Lucas Penny, Jinfeng Zou, Zhen Zhao, Yangqiao Zheng, Pamela Soberanis Pina, Michelle McMullen, Eric Y. Stutheit-Zhao, Michael M. Hoffman, Sarah E. Ferguson, Kathy Han, Eric Leung, Stephanie Lheureux, Scott V. Bratman. Human papillomavirus circulating tumor DNA for risk stratification in cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4663.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».