Prognostic Value of Human Papillomavirus (HPV) Detection in Cervical Intra-epithelial Neoplasia (CIN) Recurrence After Conization

Terminated

• Conditions: CIN2/3 Recurrence
• Interventions: Other: Study Follow-Up

• Registration Number: NCT01543048
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

CIN2/3 have been increased for many years and mainly concern women aged 25-29 years. They are subsequent to a persistent HPV infection and are classically treated by conization. Recurrences occur in 7 to 18 % of cases, mainly after CIN3 management during the first 2 years of follow-up. Follow-up is crucial to detect and treat recurrence and to select high risk women who might develop cervical cancer. Colposcopy and cytology have been recommended since 1989 by French ANAES, but these methods have poor sensitivity and specificity. However, DNA HPV testing is more sensitive and has demonstrated a very high negative predictive value, while specificity and positive predictive value remain average. Other HPV markers like genotyping, viral load and integration begin to be used in screening but have not been investigated in CIN2/3 follow-up to assess the values of various HPV markers which predict CIN2/3 recurrence after conization. The primary objective is to describe HPV expression (genotyping, viral load, mRNA E6 and E7) at the time of conization and during the follow-up period (6, 12, 24 months) and to assess the prognostic value of HPV 16 expression (viral load, mRNA E6 and E7) to determine the risk of CIN2/3 recurrence after conization, compared to the other clinical and virological risk factors.

Detailed Description

Women with CIN3 treated by conization will be consecutively included in this study during 12 months. They will be recruited in the 3 main University Hospitals of South West France (Bordeaux, Toulouse, Limoges) and followed-up for 24 months. Colposcopy (+/- biopsies), cytology, and virology tests will be performed at the time of conization and during the follow-up period (6, 12, 24 months). HPV expression will be assessed by centralized validated marketed tests (Hybrid Capture 2, RLA genotyping, PreTect® HPV-Proofer) and by a real time PCR measuring E2, E6 and E7 viral load of HPV 1.

Study Timeline

• Study First Submitted: 2012-02-27
• Study First Submitted QC: 2012-03-01
• Study First Posted: 2012-03-02
• Study Start: 2012-03-06
• Primary Completion: 2016-08-01
• Study Completion: 2016-08-01
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-22
• Last Update Posted: 2017-08-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 106

Inclusion Criteria

• Women over 18 years
• CIN 2 or 3 diagnosis at inclusion confirmed for a CIN3 diagnosis by conization.
• HPV detected by Hybrid Capture 2 or RLA genotyping.
• Informed and signed consent by the patient and the investigator
• Coverage by French social security

Exclusion Criteria

• Pregnancy at the time of inclusion.
• Previous history conization.
• Atypical endometrial or glandular cells or evidence of carcinoma on conization.
• Previous vaccination with a prophylactic HPV vaccine.
• Active viral infections including HIV.
• Acquired or congenital immunodeficiency.
• Long term treatment by corticosteroids or immunosuppressive drugs.
• Persons under protection of law.
• Patients unable to meet the requirements of the protocol.
• Any condition that, according to the investigator, would prevent participation in the study or interfere with the objectives of the study (refusal of supervision at the University Hospital, expected change of address within 3 years, etc)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Women with CIN3 treated by conization	Study Follow-Up	-

Primary Outcome Measures

Name	Time	Method
Recurrence of CIN2/3 diagnosed on colposcopy-directed biopsy	For each patient, 24 month after inclusion	Biopsies will be carried out in cases of abnormal findings by colposcopy, cytological anomalies (ASC-US, ASC-H, LSIL, HSIL, cancer), and/or colpo-cytological discordance. The prognostic impact of HPV16 compared to the other HR-HPV on the recurrence of CIN2/3 will be assessed

Secondary Outcome Measures

Name	Time	Method
Evaluation of CIN2/3 diagnosis tests	For each patient, 24 month after inclusion	Sensitivity, specificity, positive and negative predictive values of the following tests in the diagnosis of CIN2/3 after conization: * Cytology (at the ASC-US threshold); * Colposcopy (at the grade 2 abnormal transformation threshold); * Hybrid Capture 2 (positivity threshold: 2 pg/ml); * RLA genotyping (presence or not of HPV 16 and/or other HR-HPV); * PreTect® HPV-Proofer (presence or not of mRNA E6 and E7 of HPV 16, 18, 31, 33, 45)

Trial Locations

Locations (4)

CHU de Bordeaux; 🇫🇷 Bordeaux, France

CHU de Limoges, Hôpital Mère Enfant; 🇫🇷 Limoges, France

CHU de Toulouse, Hôpital Paule de Viguier; 🇫🇷 Toulouse, France

CHU de Toulouse, Hôpital Rangueil; 🇫🇷 Toulouse, France