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Cervical Cancer Prevention: From DNA to mRNA? - New Technologies for Cervical Cancer Screening 2 (NTCC2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01837693
Recruitment Status : Unknown
Verified May 2012 by Azienda Unità Sanitaria Locale Reggio Emilia.
Recruitment status was:  Not yet recruiting
First Posted : April 23, 2013
Last Update Posted : April 23, 2013
Sponsor:
Information provided by (Responsible Party):
Azienda Unità Sanitaria Locale Reggio Emilia

Brief Summary:

In industrialized countries, cervical cancer is a well controlled disease thanks to the diffusion of Pap test and, in particular, to organized screening programs, which are able to detect and treat pre-invasive lesions (cervical intraepithelial neoplasia, CIN). The human papilloma virus (HPV) has been recognised as the necessary, but not sufficient, cause of cervical cancer, so a new screening test based on the identification of high risk (HR) HPV types has been developed(HPV DNA test). This test has demonstrated to be more effective than cytology in reducing the incidence and the mortality of cervical cancer, but it is less specific, so the use of a test triage is necessary to reduce the number of colposcopies and the risk of over-diagnosis (due to the potential regressivity of pre-invasive lesions). Until now, the triage test used is the cytology (Pap test).

Recently specific biomarkers (mRNA and p16 tests) have been introduced for high grade CIN, targeting the molecular alterations strictly associated to transformation rather than simply detecting HR-HPV infections. These tests are more specific than HPV DNA test with a modest reduction of sensitivity for high-grade lesions.

This is a multicenter randomised trial nested into some Italian screening programs based on the use of HPV DNA test as primary test.

All women with positive HPV DNA test will be tested for cytology and also for mRNA and p16. Women with positive cytology will be referred to colposcopy, while women with negative cytology will be randomized into two arms.

This study aims to evaluate if mRNA and p16 could be used as test of triage of HPV DNA or as a primary screening test with direct sending in colposcopy.

In particular the main objectives are:

  • Measuring the cumulative detection rate of CIN2+ in the five years following a HPV DNA positive test and mRNA or p16 negative.
  • Measuring the potential reduction of overdiagnosis of using mRNA or p16 test instead of DNA, with direct sending in colposcopy
  • Measuring the reduction of overdiagnosis of cytological triage or triage with mRNA or p16 compared to the direct sending in colposcopy in women with HPV DNA test positive.

Secondary objectives are:

  • to assess the feasibility of mRNA testing in primary screening
  • to validate the sample techniques for the new tests
  • to standardize quality controls for the the new tests

Condition or disease Intervention/treatment Phase
Precancerous Conditions Neoplasms Procedure: Experimental: immediate colposcopy Not Applicable

Detailed Description:

Individual data about the following study steps are collected according a fixed format:

  1. recruited women
  2. HPV DNA result
  3. cytology and randomization results
  4. p16 result
  5. mRNA result
  6. colposcopies (with relative cytology and histologies) results
  7. Women excluded after informed consent
  8. Interventions During the first year of recruitment, there will be two semi-annual sending of data, then each year.

To analyze the study progress in each center, summary tables will periodically send to the PI.

All CIN lesions and cancers found in the study will be be blindly reviewed. A set of quality assurance procedures will be implemented for both the molecular tests, including the use of controls provided by the manufacturers with known HPV DNA or mRNA content and the circulation of clinical samples prepared by the laboratories participating in the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Screening
Official Title: HPV as Primary Screening Test in Cervical Cancer Prevention: From DNA to mRNA? A Randomised Controlled Trial Nested in a Double Testing Study With Long Term Follow up
Study Start Date : June 2013
Estimated Primary Completion Date : June 2015
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arm Intervention/treatment
No Intervention: one year follow up
A random sample of HPV positive women with negative cytology will be invited to repeat HPV DNA test and biomarkers after a year, as recommended by the current screening protocols based on HPV DNA
Experimental: direct sending in colposcopy
Experimental: immediate colposcopy. A random sample of HPV positive women with negative cytology will be sent to immediate colposcopy
Procedure: Experimental: immediate colposcopy
A immediate colposcopy in this arm may detect potentially spontaneous regressive cervical lesions, so may determine an over diagnosis and over treatment, which the study want to estimate




Primary Outcome Measures :
  1. cumulative incidence of CIN2+ in women with positive DNA and negative mRNA or p16 [ Time Frame: 5 years ]
    Sum of CIN2+ detected in women with positive DNA and negative mRNA or p16 tests during the entire period (5 years) divided by the total number of CIN2+ found in the study. The HPV DNA test will be the final follow-up test, since it is the most sensitive test among the candidates for screening, so it is the one that allows to estimate more accurately the prevalence of lesions.


Secondary Outcome Measures :
  1. comparison between CIN2+ detection rates in the two arms in women with p16 or mRNA negative [ Time Frame: 1 year ]
    proportion of CIN2+, HPV DNA positive and p16 or mRNA negative, which regress in a year

  2. comparison between CIN2+ detection rates in the two arms in women with negative cytology [ Time Frame: 1 year ]
    measure of how much the cytological triage can reduce overdiagnosis compared to HPV DNA with direct sending to colposcopy

  3. comparison between CIN2+ detection rate in the two arms in women with p16 or mRNA positive [ Time Frame: 1 year ]
    direct comparison of the effectiveness between a screening based on the HPV mRNA or p16 test followed by cytological triage and a screening with direct sending to colposcopy



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 59 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • women invited for a new screening round based on HPV DNA test

Exclusion Criteria:

  • women not resident in the screening area, or pregnant, or with treated CIN in the 5 previous years, or in post-colposcopy follow up, or in repetition for unsatisfactory cytology.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01837693


Contacts
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Contact: Enza Di Felice difelicee@ausl.re.it

Locations
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Italy
Unità Locale Socio-Sanitaria 17 Este Monselice
Este, Italy
Principal Investigator: Antonio Ferro         
Istituto per lo Studio e la Prevenzione Oncologica
Florence, Italy
Principal Investigator: Francesca Carozzi         
Principal Investigator: Massimo Confortini         
Azienda Sanitaria Locale 1-L'Aquila
L'Aquila, Italy
Principal Investigator: Vincenzo Maccallini         
Istituto Oncologico Veneto
Padua, Italy
Azienda Sanitaria Locale 2- Regione Umbria
Perugia, Italy
Principal Investigator: Basilio Passamonti         
Azienda Sanitaria Locale Reggio Emilia
Reggio Emilia, Italy
Principal Investigator: Luisa Paterlini         
Laziosanità - Agenzia di Sanità Pubblica della Regione Lazio
Rome, Italy
Regina Elena Cancer Institute
Rome, Italy
Azienda Sanitaria Locale Roma G
Tivoli, Italy
Principal Investigator: Maria Concetta Tufi         
Azienda Sanitaria della Provincia Autonoma di Trento
Trento, Italy
Principal Investigator: Paolo Dalla Palma         
Centro per la Prevenzione Oncologica del Piemonte
Turin, Italy
Principal Investigator: Guglielmo Ronco         
Sponsors and Collaborators
Azienda Unità Sanitaria Locale Reggio Emilia
Investigators
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Principal Investigator: Paolo Giorgi Rossi, PhD Epidemiology Service, Local Health Authority of Reggio Emilia, Italy

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Responsible Party: Azienda Unità Sanitaria Locale Reggio Emilia
ClinicalTrials.gov Identifier: NCT01837693    
Other Study ID Numbers: cervicalscreening_mRNA_p16
First Posted: April 23, 2013    Key Record Dates
Last Update Posted: April 23, 2013
Last Verified: May 2012
Keywords provided by Azienda Unità Sanitaria Locale Reggio Emilia:
cervical cancer screening
CIN
cervical cancer
biomarkers
sensitivity and specificity
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Precancerous Conditions
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female