Detection of Minimal Residual Disease Based on HPV ctDNA in Cervical Cancer

Study Overview
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Brief Summary
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In this study, a large-scale cohort of cervical cancer patients was established in multiple centers. Minimal residual disease(MRD) was assessed by ddPCR detection of HPV E7 gene ctDNA to assess tumor burden and predict the risk of disease recurrence, so as to provide new biomarkers for precise treatment of cervical cancer patients. The study continued until 36 months after the end of treatment.

Detailed Description
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The purpose of this study is to assess MRD by detecting HPV E7 gene ctDNA to assess tumor burden and predict the risk of disease recurrence. According to the treatment methods, the patients were divided into two groups :(1) initial surgical treatment group (2) initial concurrent chemoradiotherapy group. After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3 6 months within 2 years after treatment and every 6 12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary. Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, after treatment, and at 6, 12, 18, 24, 30, and 36 months of follow-up. The primary endpoint is Disease-free survival (DFS, time from the treatment initiation to disease progression). Secondary endpoints include HPV ctDNA state before treatment, dynamic change trend of HPV ctDNA after treatment and overall survival (OS, time from the treatment initiation to death).

Official Title
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Clinical Value of Minimal Residual Disease Detection Based on Human Papillomavirus Circulating Tumor DNA (HPV ctDNA) in Cervical Cancer

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Other: detect HPV E7 ctDNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathological diagnosis: cervical squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma FIGO stage: IA2-IVA HPV typing: type 16 or 18 ECOG 2-0 The initial treatment was surgery (Cohort A) / concurrent chemoradiotherapy (Cohort B) Exclusion Criteria: The diagnosis of cervical cancer was made within 3 years of other malignancies Pregnant or lactating women Refused to sign a consent form

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| initial surgical treatment group<br>After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3 6 months within 2 years after treatment and every 6 12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary. Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, 2 weeks after surgery, (1 month after adjuvent radiotherapy if available) and at 6, 12, 18, 24, 30, and 36 months of follow-up. | Other: detect HPV E7 ctDNA<br>* Peripheral blood was collected from the patients, and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR<br>|
| initial concurrent chemoradiotherapy group<br>After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3 6 months within 2 years after treatment and every 6 12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary. Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, 1 month after radiotherapy and at 6, 12, 18, 24, 30, and 36 months of follow-up. | Other: detect HPV E7 ctDNA<br>* Peripheral blood was collected from the patients, and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | time from the treatment initiation to disease progression | up to three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPV ctDNA state before treatment | Peripheral blood was collected from the patients before treatment (surgery or chemotherapy), and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR | up to three years | 
| Dynamic change trend of HPV ctDNA after treatment | Peripheral blood was collected from the patients after treatment ((2 weeks after surgery), 1 month after radiotherapy and at 6, 12, 18, 24, 30, and 36 months of follow-up), and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR | up to three years | 
| Overall Survival | time from the treatment initiation to death | up to three years |