HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer

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L. Cabel¹  C. Bonneau²  A. Bernard-Tessier⁴  D. Héquet³  C. Tran-Perennou⁴  G. Bataillon⁴  R. Rouzier³  J.-G. Féron³  V. Fourchotte³  J.-F. Le Brun⁶  C. Benoît⁷  M. Rodrigues¹  N. Scher⁸  M. Minsat⁸  M.-E. Legrier⁹  I. Bièche⁴  C. Proudhon^1,11  X. Sastre-Garau^1,12  F.-C. Bidard¹  E. Jeannot⁴ 

[1] Department of Medical Oncology, Institut Curie;UVSQ, Paris-Saclay University;Department of Surgical Oncology, Institut Curie;Department of Pathology and Genetics, Institut Curie;U900, UVSQ, Paris-Saclay University;Department of Gynecology and Obstetrics;Department of Radiation Oncology, Centre Jean Perrin;Department of Radiation Oncology, Institut Curie;Department of Research, Institut Curie;Paris University;Circulating Tumor Biomarkers Laboratory, Institut Curie;Department of Pathology, Hôpital Intercommunal de Créteil

关键词: circulating tumor DNA;    human papillomavirus;    cervical cancer;    chemoradiotherapy;    prognostic marker;   

DOI  :  10.1016/j.esmoop.2021.100154

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC.Methods We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR.Results HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013).Conclusion This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.

【 授权许可】

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