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

• Published in: Molecular oncology Vol. 18; no. 5; pp. 1231 - 1244
• Main Authors: Bønløkke, Sara, Steiniche, Torben, Sorensen, Boe Sandahl, Nyvang, Gitte‐Bettina, Lindegaard, Jacob Christian, Blaakær, Jan, Bertelsen, Jesper, Fuglsang, Katrine, Strube, Mikael Lenz, Lenz, Suzan, Stougaard, Magnus
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-05-2024; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Aged; Biomarkers; Biomarkers, Tumor - blood; Blood & organ donations; Cancer therapies; Carcinogens; Care and treatment; Cell-Free Nucleic Acids - blood; Cervical cancer; Chemotherapy; circulating HPV DNA; Denmark; Diseases; DNA; DNA, Viral - blood; DNA, Viral - genetics; Female; Gynecology; HPV; HPV integration; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Humans; Integration; Israel; Liquid Biopsies; Medical prognosis; Medical research; Medicine, Experimental; Middle Aged; Next-generation sequencing; Obstetrics; Oncology; Papillomavirus infections; Papillomavirus Infections - blood; Papillomavirus Infections - complications; Papillomavirus Infections - diagnosis; Papillomavirus Infections - virology; Patients; Plasma; Radiation therapy; Risk factors; Scientific equipment and supplies industry; Sedlis criteria; Severity of Illness Index; Surgery; United States; Uterine Cervical Neoplasms - blood; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Womens health; Denmark; United States; Israel; Aarhus Denmark; HPV integration; circulating HPV DNA; Sedlis criteria; cervical cancer; next‐generation sequencing; HPV
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1002/1878-0261.13538

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 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.
For cervical cancer (CC), circulating cell‐free HPV DNA (ccfHPV) may establish disease severity. Using targeted next‐generation sequencing of cell‐free DNA, we established ccfHPV presence and HPV16 integration status in CC patients. Our findings suggest that ccfHPV detection is related to disease severity but also influenced by HPV integration status and disease stage.