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Supplementary Figure S4 from Cell-Free Human Papillomavirus DNA Is a Sensitive Biomarker for Prognosis and for Early Detection of Relapse in Locally Advanced Cervical Cancer

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posted on 2024-07-01, 07:23 authored by Lars Sivars, Cecilia Jylhä, Ylva Crona Guterstam, Mark Zupancic, Britta Lindqvist, Magnus Nordenskjöld, Emma Tham, Kristina Hellman

Supplementary Figure S4. Kaplan–Meier graphs of comparisons between patients with ctHPV DNA–positive (dotted, bottom lines) and ctHPV DNA–negative (solid, top lines) plasma at early-follow up/tumor evaluation (1-4 month after finished treatment) plasma.

Funding

Karolinska Institutet (KI)

Magnus Bergvalls Stiftelse (Magnus Bergvall Foundation)

Region Stockholm

Cancerfonden (Swedish Cancer Society)

History

ARTICLE ABSTRACT

Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC).Experimental Design: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type–specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics.Results: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1–2 months after end-of-treatment), or tumor evaluation (3–4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P < 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time.Conclusions: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.

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