Condition category
Cancer
Date applied
29/04/2005
Date assigned
03/06/2005
Last edited
03/04/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

Sponsor information

Organisation

CPO Piemonte (Italy)

Sponsor details

Via San Francesco da Paola 31
Torino
10123
Italy

Sponsor type

Government

Website

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Additional files

Editorial Notes