Integration Pattern of Human Papillomavirus is a Strong Prognostic Factor for Disease-free Survival after Radiotherapy in Cervical Cancer Patients
Menée à partir d'échantillons tumoraux prélevés sur 98 patientes atteintes d'un cancer du col de l'utérus de stade localement avancé, puis validée sur 106 patientes complémentaires, cette étude met en évidence l'intérêt de déterminer, par hybridation in situ et PCR, le modèle d'intégration de l'ADN du papillomavirus humain dans l'ADN tumoral pour prédire la survie sans maladie après une radiothérapie
Purpose : The standard chemoradiotherapy currently used for locally advanced cervical cancer (LACC) patients does not reflect the biologic heterogeneity of this disease, and there is an increasing need for the development of biomarkers that can help guide the individualized treatment regimens. The purpose of this study is to investigate the prognostic value of the integration pattern of human papillomavirus (HPV) in LACC patients.
Patients and Methods : The HPV integration pattern was determined by in situ hybridization (ISH) and polymerase chain reaction (PCR), and the tumors were classified as the episomal pattern (group A), single-copy integrated or multi-copy tandem repetition-integrated pattern (group B), or as undetectable HPV (group C). Ninety-eight LACC patients were included in a development dataset and 106 independent patients in a validation dataset. The multivariable Cox model was used to examine the effect of the HPV integration pattern on disease-free survival (DFS). The model was validated internally using the leave-one-out cross-validation method and externally using an independent dataset.
Results : After adjusting for significant prognostic factors (stage, histologic grade, histologic type, and tumor size), the HPV integration pattern was significantly associated with DFS in the development (P=0.032) and validation (P=0.023) datasets. The survival was worst in group C and best in group A. The multivariable model with HPV integration pattern as an explanatory variable showed good discrimination ability, and could separate patients with different risk profiles.
Conclusion : This study identified the HPV integration pattern, as determined by ISH and PCR, as a strong prognostic biomarker for disease free survival in LACC patients treated by chemoradiotherapy. This finding may open the possibility of personalized treatment of these patients.
International Journal of Radiation Oncology • Biology • Physics , résumé, 2016