HPV in Blood Samples From Cervical Cancer Patients.

NCT ID: NCT03749720

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-15
• Study Completion Date: 2022-10-30

Brief Summary

By means of digital droplet PCR (ddPCR) anf targeted Next Generation Sequencing (NGS), this study examines blood samples from patients newly diagnosed with cervical cancer to investigate whether it is possible to measure the presence and amount of HPV DNA in these blood samples. The first blood sample is taken at time of diagnosis, and follow-up blood samples are collected during treatment- and follow-up visits. We expect to find a correlation between the disease stage and the viral load and also a decline in viral load after treatment. Furthermore, we hope that this method may serve as a way of detecting disease recurrence earlier than what is possible today.

Detailed Description

This study hypothesises that in patients with HPV-related cervical cancer, HPV DNA may be released into the bloodstream from tumor cells. These fragments of HPV DNA shed by tumor may therefore be measured in blood samples from the patients. By using the same setting as for real-time PCR with PCR primers and probes for fluorescence detection, the study uses digital droplet PCR (ddPCR), a method based on dilution and partitioning of the blood sample in many reaction chambers or droplets, to measure absolute quantities of HPV DNA fragments in blood samples from women with different stages of cervical cancer. Furthermore, our research group has developed in-house amplicon-based Next Generation Sequencing (NGS) assays for HPV detection and genotyping (the NGS HPV genotyping panel) and HPV integration status and variants (the HPV16 panel), and blood samples are also analysed with the NGS HPV genotyping panel. Cervical tissue samples from primary tumor are collected and analysed with the NGS HPV genotyping panel, and HPV16 positives are further analysed with the NGS HPV16 panel. Patients are recruited at the time of diagnosis, where a baseline blood sample is collected. Follow-up blood samples are collected during treatment and at follow-up visits up to two years after the diagnosis. We expect the HPV DNA load to decrease after treatment, and if an increase in viral load is detected during follow-up, we expect this to be an early sign of a disease recurrence. The method may therefore become an effective monitoring tool in these patients in terms of detecting a ongoing disease recurrence, which gives us the chance to intervene and treat these patients before the disease becomes too disseminated.

For included patients experiencing af recurrence of their disease, tissue samples from recurrent disease are collected and analysed with both the NGS HPV genotyping panel, the NGS HPV16 panel (for HPV16 positives), p16 staining, and a panel detecting relevant somatic mutations in the TP53 and RB1 tumor suppressor proteins.

Conditions

HPV-Related Carcinoma; HPV-Related Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cervical cancer patients

Baseline- and follow-up blood samples are collected from the cervical cancer patients at time of diagnosis and during treatment and clinical follow-up. HPV DNA is measured in these samples.

Group Type: OTHER

Blood sample

Intervention Type: OTHER

Blood sample taken from cervical cancer patients at time of diagnosis (baseline) and follow-up visits.

Interventions

Blood sample

Blood sample taken from cervical cancer patients at time of diagnosis (baseline) and follow-up visits.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosed with cervical cancer ≥ stage 1B between june 2018 and june 2020
• > 18 years of age at the time of diagnosis
• There must be available cervical tissue material from the patient to analyse for HPV

• Women > 18 years with no prior history of any cervical dysplasia

• Women > 18 years
• Must have a histologically verified severe cervical dysplasia (CIN3)
• Is admitted for cervical conisation

Exclusion Criteria

• < 18 years of age at time of cervical cancer diagnosis
• Cervical cancer < stage 1B

• < 18 years of age
• Prior cervical dysplasia

• < 18 years of age
• Women with only low grades of cervical dysplasia (CIN1 or CIN2)
• Women with HPV-negative cervical biopsies

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sara Bønløkke, MD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital

Locations

Department of Obstetrics and Gynecology

Aarhus, , Denmark

Department of Obstetrics and Gynecolgy

Odense, , Denmark

Countries

Denmark

Other Identifiers

U416

Identifier Type: -

Identifier Source: org_study_id