Intraoperative HPV Testing Evaluation

April 29, 2020 updated by: Hospital Universitari Vall d'Hebron Research Institute

Intraoperative HPV Testing Evaluation: Multicenter Prospective Cohort Study

High-grade intraepithelial lesion/cervical intraepithelial neoplasia grade 2-3 is a premalignant cervical lesion caused by persistent high-risk human papillomavirus infection. Human papillomavirus test is a very sensitive risk marker of cervical cancer and it has been incorporated in the follow-up after high-grade intraepithelial lesion treatment. Papillomavirus test performed intraoperatively could be a beneficial approach to anticipate treatment failure, allow for early management and consequently a reduction in costs. The aim of this study is to evaluate if the IOP-HPV test has non-inferior diagnostic utility of HSIL/CIN2-3 recurrence at 24 months as the HPV test performed 6 months after treatment.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

High-Grade Intraepithelial Lesion/Cervical Intraepithelial Neoplasia grade 2-3 (HSIL/CIN2-3) is a premalignant cervical lesion caused by persistent high-risk Human papillomavirus (HPV) infection [1]. It is estimated that approximately 54,000 women in Spain are annually diagnosed with HSIL/CIN2-3, which represents a significant economic burden for the national health system [2]. Electrosurgical excision procedure (LEEP) is the standard treatment of HSIL/CIN2-3 [3,4]. In Spain, current national guidelines recommend control after LEEP at 6, and 24 months [5,6,7]. The HPV test is a sensitive marker of cervical cancer risk and it has been incorporated, with cytology, in the follow-up of squamous cervical intraepithelial lesion after a LEEP [8,9,10].

We recently showed that an HPV test performed intraoperatively (IOP-HPV) has a strong association with recurrent disease as well as a good diagnostic recurrence efficiency at 12 months, similar than the test performed at 6 months. Thus, IOP-HPV test could be feasible and useful to identify treatment failure earlier than conventional strategies [11]. These results are similar to those previously observed by other authors [12].

However, one of the limitations of previous studies was the sample size of patients to achieve greater statistical power and perform a non-inferiority study.

The aim of this study is to evaluate if the IOP-HPV test has non-inferior diagnostic utility of HSIL/CIN2-3 recurrence at 24 months as the HPV test performed 6 months after LEEP.

Material and methods

This is a multicenter prospective cohort study that will include patients diagnosed with HSIL/CIN2-3. This study will be carried out at the Hospital Vall d'Hebron in Barcelona (organizing center) and other National centers from June 2020 to June 2024. All patients will undergo a HPV test 3 months prior to treatment and will be followed for a period of 24 months.

Cytology samples will be interpreted by an experienced pathologist following the Bethesda System [13]. HPV test will be performed using the commercially available Hybrid Capture 2 (HC2) system. If this is positive, it will be followed by the CLART-HPV2 test, a PCR technique that will allow the detection of 35 HPV genotypes.

Colposcopy will be performed using a colposcope Olympus 500 after preparing the cervix with 5% acetic acid and lugol solution. Colposcopy findings will be described following the criteria of the International Federation for Cervical Pathology and Colposcopy (IFCPC) [14].

Prior to LEEP, the abnormal area will be delimited by acetic acid and iodinated lugol, a colposcopy will be performed prior to the application of 1 ml of 2% mepivacaine to each quadrant of the cervix.

The entire pathological area will be removed next to the transformation zone (TZ), followed by selective coagulation of the surgical bed by diathermic coagulation ball. Immediately after the LEEP, a cervical sample will be taken for the IOP-HPV test. At the end of the procedure an ECC will be performed using a Novak curette.

The cervical specimen will be processed in a standardized way: after staining with ink the surfaces (or the margins) of the piece, a paraffin block will be obtained from which a minimum of 12 sections, of the 4 quadrants will be examined. A margin will be considered affected if the lesion reaches the margin or is within 1mm.

After surgery, the follow-up will be performed according to the National Guidelines Recommendations5,6,7. Visits will be scheduled according to the margin status of the LEEP specimen: If the margins are negative, the patient will be reviewed at 6, 12 and 24 months with cytology, HPV test and colposcopy. If they are positive, a visit will be added 4 months after the procedure where an additional cervical cytology will be taken.

Patients with abnormal cytology (LSIL+) or abnormal colposcopy will undergo a CGB. When the TZ is not completely visible or no colposcopic abnormalities are identified, an ECC with Novak curette will also be performed.

High-grade recurrence will be considered either when the CGB confirmes HSIL/CIN2-3 or when the ECC shows HSIL.The criteria to perform a second treatment will be the histological confirmation of HSIL/CIN2-3 during the follow-up.

Study Type

Observational

Enrollment (Anticipated)

1553

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

23 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Patients diagnosed of HSIL/CIN2-3 by colposcopy guided biopsy (CGB) or endocervical curettage (ECC) in the 3 months prior to LEEP and/or confirmation of HSIL/CIN2-3 in the pathologic study of the surgical specimen

Description

Inclusion Criteria:

  • Diagnosis of HSIL/CIN2-3 by colposcopy guided biopsy (CGB) or endocervical curettage (ECC) in the 3 months prior to LEEP and/or confirmation of HSIL/CIN2-3 in the pathologic study of the surgical specimen

Exclusion Criteria:

  • Patients with acquired or congenital immunosuppression
  • Patients undergoing chronic immunosuppressive treatments, prior treatment with LEEP
  • Patients in whom HSIL/CIN2-3 was not histologically confirmed.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
IOP VPH test
Immediately after the LEEP, a cervical sample is token for the IOP-HPV test
Diagnostic test: IOP HPV test
Immediately after the LEEP, a cervical sample was taken for the IOP-HPV test

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intraoperatory HPV testing evaluation: non- inferior study of diagnostic utility of HSIL/CIN2-3 recurrence as 6-months HPV test.
Time Frame: 24 months of follow-up after LEEP
Evaluate if the IOP-HPV test has non-inferior diagnostic utility of HSIL/CIN2-3 recurrence at 24 months as the HPV test performed 6 months after LEEP.
24 months of follow-up after LEEP

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari Vall d'Hebron Research Institute

Investigators

  • Principal Investigator: Cristina Centeno Mediavilla, PhD, Hospital Universitari Vall Hebrón
  • Principal Investigator: Melissa Bradbury Lobato, PhD, Hospital Vall d'Hebron
  • Study Chair: Antonio Gil Moreno, PhD, Hospital Vall d'Hebron
  • Principal Investigator: Jordi Rabasa Antonijuan, PhD, Hospital Vall d'Hebron

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2020

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

November 29, 2019

First Submitted That Met QC Criteria

December 5, 2019

First Posted (Actual)

December 9, 2019

Study Record Updates

Last Update Posted (Actual)

May 1, 2020

Last Update Submitted That Met QC Criteria

April 29, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IOP VPH IOP Protocol

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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