Circulating cell-free tumor human papillomavirus DNA is a promising biomarker in cervical cancer

• Published in: Gynecologic oncology 2022-10, Vol.167 (1), p.107-114
• Main Authors: Sivars, Lars, Hellman, Kristina, Crona Guterstam, Ylva, Holzhauser, Stefan, Nordenskjöld, Magnus, Falconer, Henrik, Palsdottir, Kolbrun, Tham, Emma
• Format: Article
• Language: English
• Subjects: Hematology, Oncology, and Palliative Medicine; Obstetrics and Gynecology
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2022.07.028

AbstractObjectivesTumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA) or liquid biopsy. Here, we analyze if cell-free human papillomavirus DNA (ctHPV DNA) is detectable before, during and after treatment, in patients with cervical cancer or pre-malignant lesions that may develop into cervical cancer, and whether ctHPV DNA levels were correlated to patient or tumor characteristics and outcome. Furthermore, total cell-free DNA load is studied using cfAlbumin DNA as a surrogate marker. Methods18 patients with locally advanced CC (LACC), 15 patients with early stage CC (ESCC) and 21 patients with pre-malignant lesions, all with verified HPV16, 18 or 45-positive lesions, were included. Pre- during- and post-treatment plasma were tested for HPV16, 18 & 45 and total cfDNA load using droplet digital PCR. ResultsctHPV DNA was found in 94.4% and 26.7% of pre-treatment plasma of patients with LACC and ESCC respectively, while all samples from patients with pre-malignant lesions were negative. Higher levels of ctHPV DNA were correlated to higher FIGO2018 stage. Patients with LACC and persistent ctHPV DNA at end-of-treatment had significantly worse progression-free survival (PFS) than patients who had cleared the ctHPV DNA ( p = 0.007). Patients with total ctDNA-levels above median in pre-treatment plasma had a worse PFS ( p = 0.026), compared to patients with total ctDNA-levels below median. ConclusionctHPV DNA is a promising prognostic biomarker in locally advanced cervical cancer that should be studied further for clinical use.