Circulating cfDNA and HPV as Prognostic Biomarkers for First-Line Recurrent Metastatic Cervical Cancer

A Prognostic Research on First-Line Recurrent and Metastatic Cervical Cancer Using Circulating Cell-Free DNA and Human Papillomavirus Detection

Primary Objective of this study: To investigate the correlation between longitudinal quantitative dynamics of circulating tumor DNA (ctDNA) and HPV-derived cell-free DNA (HPV cfDNA) in peripheral blood and clinical prognosis among patients with recurrent and metastatic cervical cancer who achieved complete response following standard first-line systemic therapy.

This study plans to enroll patients with recurrent and metastatic cervical cancer who attain complete response after standard first-line systemic therapy. A total of 20 mL peripheral blood will be collected from each subject every 3 months over a planned one-year period (5 sampling time points in total). Plasma separated from blood samples will be subjected to quantitative detection and comparative analysis of circulating tumor DNA (ctDNA) and HPV-derived cell-free DNA (HPV cfDNA). Tumor tissue specimens (5-10 unstained paraffin sections) will also be collected from patients at the time of recurrent disease confirmation. It is estimated that 60 patients will be recruited and followed up dynamically for 3 years to observe clinical prognosis. This is a prospective, observational single-center cohort study. Peripheral blood samples will only be collected at scheduled time points to explore novel biomarkers associated with disease recurrence.

Inclusion Criteria:

1. Histopathologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma;
2. Patients with first recurrent or metastatic cervical cancer (including primary stage IVB disease);
3. Received standard first-line therapy (TP/TC regimen plus immunotherapy ± bevacizumab);
4. Achieved complete response (CR) following standard first-line treatment;
5. Archived pathological biopsy specimens of recurrent/metastatic lesions prior to treatment available in our hospital;
6. Participated in clinical trials of pharmaceutical therapy for first-line recurrent/metastatic cervical cancer conducted at our institution;
7. Voluntarily participates in this study and provides written informed consent;
8. Agrees to serial peripheral blood collection at scheduled time points;
9. Willing to complete scheduled follow-up visits;
10. Aged ≥ 18 years old.

Exclusion Criteria:

1. History of other malignant tumors within the past 2 years;
2. Pregnant or breastfeeding women;
3. Severe concomitant diseases, including: cardiovascular diseases (e.g., uncontrolled heart failure, unstable angina, etc.); pulmonary diseases (e.g., severe chronic obstructive pulmonary disease, interstitial pneumonia and other conditions impairing respiratory function); hepatic and renal dysfunction (e.g., decompensated liver cirrhosis, severe renal failure requiring dialysis, etc.);
4. Refusal to sign informed consent;
5. Refusal to undergo serial blood collection.