Postoperative ctHPV-DNA for Recurrence Prediction and Adjuvant Treatment Decision-Making in Cervical Cancer

Dynamic ctHPV-DNA Monitoring After Radical Surgery for Cervical Cancer to Predict Recurrence Risk and Guide Adjuvant Treatment Decisions: An Exploratory Clinical Study

This prospective observational study will evaluate whether changes in circulating tumor human papillomavirus DNA (ctHPV-DNA) after radical surgery can help predict the risk of recurrence in patients with HPV-associated cervical cancer.

Blood samples will be collected before surgery and at two predefined postoperative time points. The first postoperative assessment (TP#1) will be performed 2-4 weeks after surgery and, for patients scheduled to receive adjuvant therapy, before the start of adjuvant treatment. The second assessment (TP#2) will be performed 12-16 weeks after surgery or, for patients receiving adjuvant therapy, 12-16 weeks after completion of adjuvant treatment.

Among patients who are ctHPV-DNA negative at TP#1, the study will compare those who remain negative at TP#2 with those who become ctHPV-DNA positive. The primary objective is to determine whether postoperative ctHPV-DNA dynamics are associated with disease-free survival and whether ctHPV-DNA provides additional prognostic information beyond conventional pathological risk factors.

Adjuvant treatment will not be assigned by the study and will be determined according to standard clinical guidelines, pathological risk factors, and multidisciplinary clinical assessment. The study will also explore whether ctHPV-DNA may help identify patients who could benefit from treatment escalation or, conversely, patients at sufficiently low risk who may be candidates for future treatment de-escalation strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; HPV DNA

Detailed Description

This is a prospective, single-center, observational cohort study designed to evaluate the prognostic value of serial circulating tumor human papillomavirus DNA (ctHPV-DNA) monitoring after radical surgery for HPV-associated cervical cancer and to explore its potential role in postoperative adjuvant treatment decision-making.

Eligible patients will have histologically confirmed HPV-associated cervical cancer and will undergo radical hysterectomy with pelvic lymph node assessment, with or without para-aortic lymph node assessment as clinically indicated. Adjuvant treatment will not be assigned by the study. Decisions regarding postoperative radiotherapy, chemoradiotherapy, systemic therapy, or observation will be made according to current clinical guidelines, postoperative pathological risk factors, and multidisciplinary clinical assessment.

Peripheral blood will be collected at three predefined time points: before surgery; TP#1, 2-4 weeks after surgery and before initiation of adjuvant therapy when adjuvant treatment is planned; and TP#2, 12-16 weeks after surgery for patients not receiving adjuvant therapy or 12-16 weeks after completion of adjuvant therapy for patients receiving postoperative treatment. ctHPV-DNA will be assessed using a tumor-informed HPV-specific detection approach based on droplet digital polymerase chain reaction (ddPCR) or next-generation sequencing (NGS), depending on HPV genotype and platform applicability. Both qualitative detection status and quantitative ctHPV-DNA levels will be recorded.

The primary analysis will focus on patients who are ctHPV-DNA negative at TP#1 and who are alive and free of radiologically evident recurrence at TP#2. According to ctHPV-DNA status at TP#2, these patients will be classified into two major dynamic groups: persistently negative (negative at TP#1 and negative at TP#2) and molecular conversion to positive (negative at TP#1 and positive at TP#2). Patients who are ctHPV-DNA positive at TP#1 will be followed as a separate high-risk molecular residual disease cohort and analyzed descriptively.

The primary outcome is disease-free survival (DFS), assessed from the TP#2 landmark date to the first occurrence of radiologically or pathologically confirmed recurrence, death, or last follow-up. Secondary outcomes include overall survival, locoregional recurrence-free survival, distant metastasis-free survival, the interval between ctHPV-DNA conversion to positivity and clinically or radiologically detected recurrence, the association between quantitative ctHPV-DNA levels and DFS, and ctHPV-DNA clearance after adjuvant treatment.

The study will further assess whether postoperative ctHPV-DNA dynamics provide incremental prognostic information beyond established clinicopathological risk factors, including Sedlis- and Peters-based risk stratification. Exploratory analyses will compare outcomes according to receipt of adjuvant therapy within ctHPV-DNA-defined subgroups. Because treatment is not randomized, these analyses will be considered hypothesis-generating, and multivariable regression and propensity score-based methods may be used to reduce confounding.

The overall aim is to determine whether serial postoperative ctHPV-DNA monitoring can improve recurrence-risk stratification after radical surgery for cervical cancer and provide prospective evidence to support future interventional trials of ctHPV-DNA-guided escalation or de-escalation of adjuvant therapy.

• Study Type: Observational
• Enrollment (Estimated): 580

Contacts and Locations

• Study Contact: Name: Ying Zhou; Phone Number: 0551-62283954; Email: caddiezy@ustc.edu.cn

Study Locations

• China
  • Hefei, China
    • Anhui province hospital
    • Contact: Yi Liu; Phone Number: +8615755149324; Email: liuyi0428@mail.ustc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with HPV-associated cervical cancer undergoing radical surgical treatment at Anhui Provincial Hospital will be prospectively recruited. Eligible participants will have a trackable tumor-associated HPV genotype identified in tumor tissue or plasma and will undergo serial ctHPV-DNA assessment before surgery and at predefined postoperative time points. Participants will receive postoperative adjuvant treatment or observation according to standard clinical guidelines, pathological risk factors, and multidisciplinary clinical assessment. Treatment allocation will not be determined by this observational study.

Description

Inclusion Criteria:

• Age ≥18 years.
• Histologically confirmed cervical cancer, including squamous cell carcinoma, HPV-associated adenocarcinoma, or adenosquamous carcinoma.
• FIGO 2018 stage IB1-II cervical cancer undergoing radical surgical treatment; selected patients with postoperative pelvic lymph node metastasis may also be included.
• Undergoing radical hysterectomy with pelvic lymph node dissection, with or without para-aortic lymph node dissection, including sentinel lymph node assessment when applicable.
• A high-risk or intermediate-risk HPV genotype detectable in baseline tumor tissue or plasma, allowing establishment of a trackable ctHPV-DNA target.
• Ability and willingness to undergo serial blood collection and clinical follow-up according to the study protocol.
• Written informed consent.
• For patients who received neoadjuvant chemotherapy, pretreatment ctHPV-DNA information must be available and a trackable HPV target must remain identifiable before surgery or during the early postoperative period.

Exclusion Criteria:

• HPV-independent cervical cancer, including gastric-type adenocarcinoma or confirmed HPV-negative squamous cell carcinoma.
• Pelvic radiotherapy administered before radical surgery.
• No residual cervical tumor after conization and inability to establish a reliable baseline HPV target for ctHPV-DNA monitoring.
• Concurrent active HPV-associated malignancy other than cervical cancer.
• Inability to comply with the scheduled blood collection or follow-up procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
HPV-Associated Cervical Cancer Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-Free Survival (DFS) According to Postoperative ctHPV-DNA Dynamic Status	Disease-free survival (DFS) is defined as the time from the TP#2 ctHPV-DNA assessment to the first occurrence of radiologically or pathologically confirmed cervical cancer recurrence, death from any cause, or last follow-up. The primary analysis will compare DFS between patients who remain ctHPV-DNA negative from TP#1 to TP#2 and those who convert from ctHPV-DNA negative at TP#1 to positive at TP#2.	From TP#2 to recurrence, death, or last follow-up, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from the TP#2 ctHPV-DNA assessment to death from any cause or last follow-up.	From TP#2 to death or last follow-up, up to 2 years
Locoregional Recurrence-Free Survival	Time from the TP#2 ctHPV-DNA assessment to the first radiologically or pathologically confirmed locoregional recurrence, death, or last follow-up.	From TP#2 to locoregional recurrence, death, or last follow-up, up to 2 years
Distant Metastasis-Free Survival	Time from the TP#2 ctHPV-DNA assessment to the first radiologically or pathologically confirmed distant metastasis, death, or last follow-up.	From TP#2 to distant metastasis, death, or last follow-up, up to 2 years
Lead Time of Molecular Recurrence Detected by ctHPV-DNA	The interval between the first postoperative conversion of ctHPV-DNA from negative to positive and subsequent radiologically or pathologically confirmed cervical cancer recurrence.	Time Frame:

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association Between Quantitative ctHPV-DNA Level and Disease-Free Survival	Quantitative ctHPV-DNA levels will be analyzed as a continuous variable to evaluate their association with DFS. ctHPV-DNA values will be log10-transformed for statistical modeling.	ctHPV-DNA assessed at TP#1 and TP#2; DFS assessed for up to 2 years after TP#2
ctHPV-DNA Clearance After Adjuvant Therapy	Among evaluable patients receiving postoperative adjuvant therapy, ctHPV-DNA clearance will be assessed by comparing ctHPV-DNA status before adjuvant treatment with that at TP#2. The association between ctHPV-DNA clearance and DFS will also be explored.	From pre-adjuvant TP#1 assessment to TP#2, approximately 12-16 weeks after completion of adjuvant therapy

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: August 20, 2026
• First Submitted That Met QC Criteria: August 20, 2026
• First Posted (Actual): August 24, 2026

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: ZhouYing-ctHPV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No