Contact information
Type
Scientific
Primary contact
Dr Guglielmo Ronco
ORCID ID
Contact details
Via San Francesco da Paola 31
Torino
10123
Italy
+39 (0)116333850
guglielmo.ronco@cpo.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
NTCC
Study hypothesis
Women who test negative in the experimental arm have a lower risk than women who test negative in the conventional arm of having a high-grade pre-invasive lesion detected in the three years following screening, therefore allowing longer screening intervals.
Ethics approval
The NTCC study was approved by the local research ethics committees of the participating centres. Ethical approval was obtained by the Dutch Ministry of Health, Welfare, and Sport for the NETHCON trial
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Screening
Patient information sheet
Condition
Cervical cancer
Intervention
Women in conventional arm have conventional cytology and are referred for colposcopy according to the standard regular protocols.
Experimental arm follows two phases:
In phase 1, women have both liquid based cytology and human papillomavirus (HPV) testing (by Hybrid Capture 2) for high risk types. Women aged 35 years or more are referred for colposcopy if either HPV is positive or cytology is atypical cells of undetermined significance (ASCUS) or more severe. Women of age less than 35 are directly referred for colposcopy if cytology is ASCUS or more severe. If HPV is positive but cytology is less than ASCUS women are invited for repeating both tests after one year and referred for cytology if either is positive.
In phase 2, women in the experimental arm are tested only for HPV and are referred for colposocpy if it is positive, independently of age.
Women in both arms are be recalled for new screening by conventional cytology after three years. The detection of CIN2+ after recruitment and up to re-screening included will be compared.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
The primary outcome measure is the detection rate (DR) of histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+). In order to test the study hypothesis we will consider DR of CIN2+ after recruitment and up to including re-screening among women who tested negative at recruitment. The DR of CIN2+ at recruitment will be studied in order to investigate the cross sectional sensitivity of new technologies compared to conventional cytology (hypothesis: higher DR in experimental arm). The overall DR at recruitment and up to including re-screening in the two arms will be compared in order to study the relative over-diagnosis of regressive lesions.
Secondary outcome measures
Main secondary outcome measures are the referral rate to colposcopy and the positive predictive value for CIN2+ in the two study arms.
Overall trial start date
01/02/2002
Overall trial end date
31/12/2004
Reason abandoned
Eligibility
Participant inclusion criteria
Women 25 to 60 years old coming for a new screening episode in nine organised cervical screening programmes
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
94,000
Participant exclusion criteria
1. Virgin
2. Pregnant
3. Hysterectomised
4. Treated for cervical cancer or intraepithelial lesions in last five years
Recruitment start date
01/02/2002
Recruitment end date
31/12/2004
Locations
Countries of recruitment
Italy
Trial participating centre
Via San Francesco da Paola 31
Torino
10123
Italy
Funders
Funder type
Government
Funder name
Italian Ministry of Health (Italy) - progetto speciale "Valutazione di nuove tecnologie per lo screening del cervicocarcinoma" and progetto speciale "Nuove tecnologie per lo screening del cervicocarcinoma. Follow-up"
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
European Union (Belgium) - Europe Against Cancer contracts SI2.327046 and SPC.2002475
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Regional Administrations of the Italian Regions involved (Piemonte, Veneto, Emilia-Romagna, Toscana, Lazio and Provncia Autonoma di Trento)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16814206
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17517761
3. 2008 results of blind revision of historic lesions in http://www.ncbi.nlm.nih.gov/pubmed/18089491
4. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20604775
4. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20089449
5. 2010 age-specific patterns of unsatisfactory results in http://www.ncbi.nlm.nih.gov/pubmed/20604775
6. 2013 results of nested substudy in http://www.ncbi.nlm.nih.gov/pubmed/23261355
Publication citations
-
Results
Ronco G, Giorgi-Rossi P, Carozzi F, Dalla Palma P, Del Mistro A, De Marco L, De Lillo M, Naldoni C, Pierotti P, Rizzolo R, Segnan N, Schincaglia P, Zorzi M, Confortini M, Cuzick J, , Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial., Lancet Oncol., 2006, 7, 7, 547-555, doi: 10.1016/S1470-2045(06)70731-8.
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Results
Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, Ghiringhello B, Giorgi-Rossi P, Minucci D, Parisio F, Pojer A, Schiboni ML, Sintoni C, Zorzi M, Segnan N, Confortini M, Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial., BMJ, 2007, 335, 7609, 28, doi: 10.1136/bmj.39196.740995.BE.
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Results of blind revision of historic lesions
Dalla Palma P, Giorgi Rossi P, Collina G, Buccoliero AM, Ghiringhello B, Lestani M, Onnis G, Aldovini D, Galanti G, Casadei G, Aldi M, Gomes V, Giubilato P, Ronco G, , The risk of false-positive histology according to the reason for colposcopy referral in cervical cancer screening: a blind revision of all histologic lesions found in the NTCC trial., Am. J. Clin. Pathol., 2008, 129, 1, 75-80, doi: 10.1309/EWYGWFRRM8798U5P.
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Results
Castle PE, Bulten J, Confortini M, Klinkhamer P, Pellegrini A, Siebers AG, Ronco G, Arbyn M, Age-specific patterns of unsatisfactory results for conventional Pap smears and liquid-based cytology: data from two randomised clinical trials., BJOG, 2010, 117, 9, 1067-1073, doi: 10.1111/j.1471-0528.2010.02650.x.
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Results
Ronco G, Giorgi-Rossi P, Carozzi F, Confortini M, Dalla Palma P, Del Mistro A, Ghiringhello B, Girlando S, Gillio-Tos A, De Marco L, Naldoni C, Pierotti P, Rizzolo R, Schincaglia P, Zorzi M, Zappa M, Segnan N, Cuzick J, , Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial., Lancet Oncol., 2010, 11, 3, 249-257, doi: 10.1016/S1470-2045(09)70360-2.
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Results of nested substudy
Carozzi F, Gillio-Tos A, Confortini M, Del Mistro A, Sani C, De Marco L, Girlando S, Rosso S, Naldoni C, Dalla Palma P, Zorzi M, Giorgi-Rossi P, Segnan N, Cuzick J, Ronco G, , Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: a prospective analysis of a nested substudy of the NTCC randomised controlled trial., Lancet Oncol., 2013, 14, 2, 168-176, doi: 10.1016/S1470-2045(12)70529-6.