Minimal residual disease in cervical cancer: biological persistence, ctHPV DNA-guided surveillance, and recurrence-directed intervention.
- 1Department of Obstetrics and Gynecology, Ninghai Maternal and Child Health Hospital, Ningbo, China.
- 2Department of Traditional Chinese Medicine, Maternity & Child Care Center Of DeZhou, Dezhou, China.
- 3Department of Thoracic Surgery, Ninghai First Hospital, Ningbo, China.
Abstract
Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, with approximately 30-40% of patients experiencing recurrence after definitive chemoradiotherapy for locally advanced disease. The concept of minimal residual disease (MRD)-the persistence of viable tumor clones after curative-intent treatment that escape conventional radiographic and clinical detection-has transformed surveillance and treatment paradigms in hematological malignancies and, increasingly, in solid tumors. In cervical cancer, the near-universal association with high-risk human papillomavirus (HPV) provides a unique molecular handle for MRD detection: circulating tumor HPV DNA (ctHPV DNA) released into the bloodstream by residual tumor cells. Here, we review three interconnected dimensions of MRD in cervical cancer. First, we examine the biological basis of tumor persistence after chemoradiotherapy, encompassing HPV integration-driven genomic instability, immune evasion within the irradiated tumor microenvironment, and clonal repopulation kinetics. Second, we synthesize the rapidly maturing evidence for ctHPV DNA-guided post-treatment surveillance, from digital PCR and next-generation sequencing-based detection platforms to prospective clinical validation studies demonstrating that detectable ctHPV DNA after chemoradiotherapy independently predicts recurrence with lead times of 3-6 months before radiographic progression. Third, we evaluate emerging recurrence-directed intervention strategies, including MRD-stratified treatment intensification (immune checkpoint inhibition and therapeutic HPV vaccination), adoptive cell therapy, and how integrating ctHPV DNA dynamics with immunotherapeutic approaches may define a new framework for personalized post-treatment management in this molecularly tractable malignancy.
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BibTeX
@article{wu2026minimal,
title = {{Minimal residual disease in cervical cancer: biological persistence, ctHPV DNA-guided surveillance, and recurrence-directed intervention.}},
author = {Jing Wu and Teng Wang and Chunyue Sheng and Wenhui Wang},
journal = {Frontiers in oncology},
year = {2026},
month = sep,
doi = {10.3389/fonc.2026.1938965},
url = {https://europepmc.org/article/MED/42840751},
note = {CC BY},
}
RIS
TY - JOUR
TI - Minimal residual disease in cervical cancer: biological persistence, ctHPV DNA-guided surveillance, and recurrence-directed intervention.
AU - Jing Wu
AU - Teng Wang
AU - Chunyue Sheng
AU - Wenhui Wang
PY - 2026
DA - 2026/09/22
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1938965
UR - https://europepmc.org/article/MED/42840751
AB - Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, with approximately 30-40% of patients experiencing recurrence after definitive chemoradiotherapy for locally advanced disease. The concept of minimal residual disease (MRD)-the persistence of viable tumor clones after curative-intent treatment that escape conventional radiographic and clinical detection-has transformed surveillance and treatment paradigms in hematological malignancies and, increasingly, in solid tumors. In cervical cancer, the near-universal association with high-risk human papillomavirus (HPV) provides a unique molecular handle for MRD detection: circulating tumor HPV DNA (ctHPV DNA) released into the bloodstream by residual tumor cells. Here, we review three interconnected dimensions of MRD in cervical cancer. First, we examine the biological basis of tumor persistence after chemoradiotherapy, encompassing HPV integration-driven genomic instability, immune evasion within the irradiated tumor microenvironment, and clonal repopulation kinetics. Second, we synthesize the rapidly maturing evidence for ctHPV DNA-guided post-treatment surveillance, from digital PCR and next-generation sequencing-based detection platforms to prospective clinical validation studies demonstrating that detectable ctHPV DNA after chemoradiotherapy independently predicts recurrence with lead times of 3-6 months before radiographic progression. Third, we evaluate emerging recurrence-directed intervention strategies, including MRD-stratified treatment intensification (immune checkpoint inhibition and therapeutic HPV vaccination), adoptive cell therapy, and how integrating ctHPV DNA dynamics with immunotherapeutic approaches may define a new framework for personalized post-treatment management in this molecularly tractable malignancy.
SN - 2234-943X
ER -