Circulating cell‐free HPV DNA is a strong marker for disease severity in cervical cancer

Abstract

For cervical cancer (CC), circulating cell‐free HPV DNA (ccfHPV) may establish disease severity. Furthermore, HPV integration has been correlated to viral load and survival. In this study, pre‐treatment plasma from 139 CC cases (50 primary surgery patients, 22 primary surgery+adjuvant oncological therapy patients, and 67 primary oncological therapy patients) was collected (2018–2020). Furthermore, plasma from 25 cervical intraepithelial neoplasia grade 3 (CIN3) patients and 15 healthy women (negative controls) were collected. Two next‐generation sequencing (NGS) panels were used to establish ccfHPV presence and human papillomavirus type 16 (HPV16) integration status. ccfHPV was detected in four primary surgery (8.0%), eight primary surgery+adjuvant oncology (36.4%), and 54 primary oncology (80.6%) patients. For primary oncology patients with HPV16‐related cancer (n=37), more ccfHPVneg than ccfHPVpos patients had HPV16 integration (p=0.04), and, in patients with HPV16 integration (n=13), ccfHPVpos patients had higher disease stages than ccfHPVneg patients (p=0.05). In summary, ccfHPV presence is related to disease severity and may add to the debated Sedlis criteria used for identifying patients for adjuvant oncological therapy. However, ccfHPV detection is influenced by HPV integration status and disease stage, and these factors need to be considered in ccfHPVneg patients.

Decoding HPV: disease stage and treatment insights

“…Recently, circulating cell-free HPV (ccfHPV) DNA was identified in the plasma from patients with cervical cancer and its levels were related to tumour burden in advanced stage cervical cancer [7]. In this issue of Molecular Oncology, Bønløkke et al [8] assessed the integration status of HPV16 and investigated whether plasma ccfHPV DNA could be a marker for disease severity using next-generation sequencing (NGS) HPV genotyping panels.…”

“…The integrated HPV DNA can induce transcriptional upregulation in vicinity or transcription of oncogenes through long-range chromatin interactions [4] and the level of ccfHPV DNA is related to disease severity [7]. In addition, plasma IL-8/IL-18 levels can be used as biomarkers for predicting therapy response in HPV-related cancers [8]. patients' peripheral blood cells who received valproic acid (histone deacetylase inhibitor) and avelumab (anti-PD-L1), as a part of the LATENT Clinical Trial study.…”