Clinical trial · Interventional
Cervical Cancer Prevention: From DNA to mRNA? - New Technologies for Cervical Cancer Screening 2
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Neoplasms | Neoplasm | ONTOLOGY_EXACT | 0.90 |
| Precancerous Conditions | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Experimental: immediate colposcopy | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- NO_INTERVENTION
- label
- one year follow up
- description
- 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
- type
- EXPERIMENTAL
- label
- direct sending in colposcopy
- description
- Experimental: immediate colposcopy. A random sample of HPV positive women with negative cytology will be sent to immediate colposcopy
- interventionNames
- Procedure: Experimental: immediate colposcopy
Primary outcomes (1)
- measure
- cumulative incidence of CIN2+ in women with positive DNA and negative mRNA or p16
- timeFrame
- 5 years
- description
Eligibility
Eligibility (as posted)
- Sex
- Female
- Minimum age
- 25 Years
- Maximum age
- 59 Years
Show eligibility criteria text
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.
References
Publications (3)
- DERIVEDDel Mistro A, Mancuso P, Carozzi F, De Marco L, Bisanzi S, Pompeo G, Ronco G, Gori S, Allia E, Gustinucci D, Frayle H, Iossa A, Cesarini E, Bulletti S, Passamonti B, Viti J, Toniolo L, Venturelli F, Giorgi Rossi P, Benevolo M; NTCC2 Working Group. Impact of differentiating between persistent and new infections on colposcopy referral in HPV-positive triage-negative women: results from the NTCC2 study. Infect Agent Cancer. 2025 Nov 20;20(1):84. doi: 10.1186/s13027-025-00713-8. PMID 41261407
- DERIVEDDe Marco L, Bisanzi S, Ronco G, Mancuso P, Carozzi F, Allia E, Rizzolo R, Gustinucci D, Frayle H, Viti J, Iossa A, Cesarini E, Bulletti S, Passamonti B, Gori S, Toniolo L, Venturelli F, Del Mistro A, Giorgi Rossi P, Benevolo M; NTCC2 Working Group. Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study. Microbiol Spectr. 2025 Jan 7;13(1):e0089724. doi: 10.1128/spectrum.00897-24. Epub 2024 Nov 22. PMID 39576120
- DERIVEDBenevolo M, Mancuso P, Allia E, Gustinucci D, Bulletti S, Cesarini E, Carozzi FM, Confortini M, Bisanzi S, Rubino T, Rollo F, Marchi N, Farruggio A, Pusiol T, Venturelli F, Giorgi Rossi P; New Technologies for Cervical Cancer 2 (NTCC2) Working Group. Determinants of p16/Ki-67 adequacy and positivity in HPV-positive women from a screening population. Cancer Cytopathol. 2021 May;129(5):383-393. doi: 10.1002/cncy.22385. Epub 2020 Nov 3. PMID 33142029