Cell Free DNA, Cervical Cancer Recurrent, HPV, Radiotherapy
Conditions
Keywords
cervical cancer, cfDNA, radiotherapy
Brief summary
The HART (HPV After chemoRadiotherapy) study is a prospective multicenter observational trial designed to evaluate the clinical utility of HPV testing in the follow-up of patients treated with definitive chemoradiotherapy (CRT) for cervical cancer. Current surveillance after CRT relies mainly on clinical examination and imaging, while the role of HPV-based molecular monitoring remains insufficiently defined. The study plans to enroll 120 patients with FIGO stage IB-IVA cervical cancer treated with primary radiotherapy with curative intent. HPV detection will be performed using two complementary approaches: PCR-based detection of HPV DNA from a cervical swab and analysis of circulating HPV tumor DNA (ctDNA) in peripheral blood. Samples will be collected before treatment and during follow-up at 3, 12, and 24 months after completion of CRT. The primary objective is to determine the sensitivity of these methods for detecting disease recurrence during a two-year follow-up period. Secondary objectives include evaluation of HPV clearance after treatment, comparison of HPV genotypes before and after therapy in cases of persistence, and comparison of the diagnostic performance of cervical HPV testing and ctDNA detection. The study aims to generate evidence supporting the integration of HPV-based molecular monitoring into routine follow-up, potentially enabling earlier detection of recurrence and more individualized surveillance strategies for patients after CRT for cervical cancer.
Interventions
None listed
Sponsors
General University Hospital, Prague
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient indicated for primary RT for cervical cancer * FIGO stage IB - IVA * Signed informed consent * Age ≥ 18 years * Administration of RT with curative intent
Exclusion criteria
* Clinical stage FIGO IA * Clinical stage FIGO IVB * History of radiotherapy in the pelvis * Hysterectomy performed before the start of radiotherapy (adjuvant RT) * History of HPV-associated malignancy in personal history * HIV or other significant immunodeficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of recurrence detection using Real Time PCR HPV DNA from a cervical swab in patients after (chemo)radiotherapy administered for cervical cancer | 2 years | Sensitivity will be calculated as the proportion of patients who tested HPV-positive after (chemo)radiotherapy (Visit 1) among all patients who developed recurrence during the two-year follow-up. |
| Sensitivity of recurrence detection using circulating HPV DNA fragments in the peripheral blood of patients after (chemo)radiotherapy for cervical cancer | 2 years | Sensitivity will be calculated as the proportion of patients with detectable circulating HPV DNA in peripheral blood after (chemo)radiotherapy (Visit 1) among all patients who developed recurrence during the two-year follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of PCR HPV DNA negativity from a swab after CRT administration | 3 months (from the start of radiotherapy) | Proportion of patients with a negative HPV test by real-time PCR from a cervical swab after (chemo)radiotherapy (Visit 1) among patients who were HPV-positive before treatment (Screening). |
| Rate of HPV negativity based on detection of circulating HPV DNA fragments in peripheral blood after CRT. | 3 months (from the start of radiotherapy) | Proportion of patients with an undetectable level of circulating HPV DNA in peripheral blood after completion of (chemo)radiotherapy (Visit 1) among patients in whom circulating HPV DNA was detected before treatment (Screening). |
| Comparison of the sensitivity of recurrence detection using HPV DNA PCR from cervical swabs versus detection of circulating HPV DNA fragments in peripheral blood. | 2 years | The sensitivities of the two tests will be compared using receiver operating characteristic (ROC) curve analysis. |
| Evaluation of the course of further treatment (especially the possibility of curability) in patients who were detected with recurrence during the study | 2 years | Proportion of patients with recurrence who underwent curative surgery (with complete resection of the recurrent tumor) among those who developed recurrence. |
Countries
Czechia
Contacts
CONTACTLukas Dostalek, MD, PhD
Outcome results
None listed