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REVIEW

Circulating Tumor DNA in Cervical Cancer: Clinical Utility and Medico-Legal Perspectives

Abdulrahman K. Sinno1, Aisha Mustapha1, Navya Nair1, Simona Zaami2, Lina De Paola2, Valentina Billone3, Eleonora Conti3, Giuseppe Gullo3,*, Pasquale Patrizio4
1 Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2 Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Rome, 00161, Italy
3 Department of Obstetrics and Gynecology, AOOR Villa Soffa–Cervello, University of Palermo, Palermo, 90127, Italy
4 Division of Reproductive Endocrinology & Infertility, University of Miami Miller School of Medicine, Miami, FL 33136, USA
* Corresponding Author: Giuseppe Gullo. Email: gullogiuseppe@libero.it

Oncology Research https://doi.org/10.32604/or.2025.072176

Received 21 August 2025; Accepted 29 October 2025; Published online 19 November 2025

Abstract

Cervical cancer related to human papillomavirus (HPV) is a leading cause of cancer-related mortality among women worldwide. Cancer cells release fragments of their DNA, known as circulating tumor DNA (ctDNA), which can be detected in bodily fluids. A PubMed search using the terms “ctHPV” or “circulating tumor DNA” and “cervical cancer”, limited to the past ten years, identified 104 articles, complemented by hand-searching for literature addressing medico-legal implications. Studies were evaluated for relevance and methodological quality. Detection and characterization of circulating tumor HPV DNA (ctHPV DNA) have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer. Detection techniques include polymerase chain reaction (PCR), digital droplet PCR (ddPCR), and next-generation sequencing (NGS). This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications, including management of discordant results, diagnostic errors, liability, and data protection compliance.

Keywords

Circulating tumor DNA; circulating tumor human papillomavirus; cervical cancer; medico-legal implications

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