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

Sep 29, 2026

Cervical cancer linked to human papillomavirus (HPV) remains a major cause of cancer mortality among women globally. Tumor cells release circulating tumor DNA (ctDNA) fragments into bodily fluids, enabling noninvasive detection. A literature search using ctHPV or circulating tumor DNA and cervical cancer, restricted to the previous decade, identified 104 articles, supplemented by targeted hand searching for medico-legal issues. Detection and characterization of circulating tumor HPV DNA support prognosis and recurrence assessment, using methods such as PCR, ddPCR, and NGS, while the review addresses discordant results, diagnostic errors, liability, and data protection compliance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Abstract

Key Findings

Detection methods (PCR, ddPCR, NGS)

Background: Cervical cancer and HPV

Burden and screening/vaccination impact

Treatment pathways by stage

Biomarkers and recurrence assessment

Imaging and biopsy requirements

SCCA and PET/CT evidence

Scope of the review

Circulating cell-free DNA and ctHPV DNA

Tech Science Press Doi:10.32604/or.2025.072176 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, * and 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 Sofia–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](Corresponding Author: Giuseppe Gullo. Email: gullogiuseppe@libero.it) [Received: 21 August 2025](Received: 21 August 2025); [Accepted: 29 October 2025](Accepted: 29 October 2025); [Published: 30 December 2025](Published: 30 December 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 1 Introduction Worldwide, cervical cancer is the fourth most common and most lethal cancer in women [1] . In 2020, there were 604,127 new cervical cancer cases and 341,831 cervical cancer deaths in the world [1] . About 90% of cases of cervical cancer occur in lower-and middle-income countries (LMICs) [1], with most cases presenting in late stages. High-income countries, on the other hand, have seen a 70% reduction in the incidence and mortality due to organized screening programs and HPV vaccination [1,2] . Early-stage disease is usually treated surgically, with sentinel lymph node (SLN) mapping improving staging accuracy and reducing morbidity compared to lymphadenectomy [3] . Locally advanced cervical cancer is treated with chemotherapy/immunotherapy and external beam radiation followed by high-dose brachytherapy, while metastatic or recurrent disease relies on systemic chemotherapy, with or without checkpoint inhibitors [4] . Despite advancements in cervical cancer treatment, recurrence rates remain high [5]. The detection of recurrence relies on patient symptoms and pelvic examination, followed by imaging Copyright © 2026 The Authors. Published by Tech Science Press. This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. when either is positive. Ultimately, a tissue biopsy is needed to confirm the diagnosis of recurrence. Thereis currently no universally accepted serologic biomarker for detection, monitoring of treatment response, or determination of recurr

FAQs

What is circulating tumor DNA (ctDNA) and why is it relevant to cervical cancer?

ctDNA consists of DNA fragments released by cancer cells into bodily fluids. In cervical cancer, circulating tumor HPV DNA (ctHPV DNA) can be detected and used to support prognosis and monitoring for recurrence.

How are ctHPV DNA tests typically performed?

The review describes detection techniques including polymerase chain reaction (PCR), digital droplet PCR (ddPCR), and next-generation sequencing (NGS). These methods enable detection and characterization of ctHPV DNA.

What medico-legal issues does the review address regarding ctHPV DNA testing?

The review explores clinical and medico-legal implications, including management of discordant results, diagnostic errors, liability considerations, and data protection compliance.

Sep 29, 2026

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