Intraoperative HPV Testing Evaluation

NCT ID: NCT04190472

Last Updated: 2020-05-01

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1553 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2024-06-01

Brief Summary

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.

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.

Conditions

HSIL, High Grade Squamous Intraepithelial Lesions; Recurrence

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

IOP VPH test

Immediately after the LEEP, a cervical sample is token for the IOP-HPV test

IOP HPV test

Intervention Type: DIAGNOSTIC_TEST

Immediately after the LEEP, a cervical sample was taken for the IOP-HPV test

Interventions

IOP HPV test

Immediately after the LEEP, a cervical sample was taken for the IOP-HPV test

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 25 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cristina Centeno Mediavilla, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitari Vall Hebron

Melissa Bradbury Lobato, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Vall d'Hebron

Antonio Gil Moreno, PhD

Role: STUDY_CHAIR

Hospital Vall d'Hebron

Jordi Rabasa Antonijuan, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Vall d'Hebron

Central Contacts

Jordi Rabasa Antonijuan, PhD

Role: CONTACT

jordi2546@hotmail.com

93 489 3066

Cristina Centeno Mediavilla, PhD

Role: CONTACT

mccenteno@vhebron.net

93 489 3066

References

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Related Links

http://www.aepcc.org/wp-content/uploads/2016/01/AEPCC_revista02.pdf

Guía de cribado del cáncer de cuello de útero en España, 2014. Editado por Asociación Española de Patología Cervical y Colposcopia ISBN: 978-84-608-36551.

Other Identifiers

IOP VPH IOP Protocol

Identifier Type: -

Identifier Source: org_study_id