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