Pilot project on the use of HPV DNA testing as primary screening test for cervical cancer precursors

ISRCTN	ISRCTN41319771
DOI	https://doi.org/10.1186/ISRCTN41319771
Secondary identifying numbers	N/A

Submission date: 01/03/2010
Registration date: 25/03/2010
Last edited: 25/03/2010

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Guglielmo Ronco
Scientific

Via San Francesco da Paola 31
Torino
10123
Italy

Phone	+390116333850
Email	guglielmo.ronco@cpo.it

Study information

Study design	Interventional pragmatic open label multicentre cluster randomised controlled study.
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Screening
Participant information sheet	Not available in web format, please use contact details below to request a patient information sheet
Scientific title	Pilot project on the use of HPV DNA testing as primary screening test for cervical cancer precursors: A multicentre randomised controlled trial
Study acronym	PROPH
Study objectives	Available scientific data show that testing for the DNA of high-risk types of human papilloma virus (HPV) is more sensitive than cytology in detecting high-grade cervical intraepithelial lesions. Four randomised controlled trials (RCTs) conducted in industrialised countries showed that HPV based screening allows earlier detection than cytology of persistent high-grade intraepithelial lesions. One of them also showed increased effectiveness, compared to cytology, in preventing invasive cervical cancer. A RCT conducted in rural India showed increased effectiveness of HPV testing vs. cytology in preventing the incidence of advanced (stage 2+) cervical cancers and death from cervical cancer. RCT results suggest the same protection, independent of having used HPV testing alone or in combination with cytology as primary screening test. In addition protection seems to be the same if all HPV positive women are referred to colposcopy or if cytological triage (as described below) is applied. On the other hand the positive predictive value of referral to cytology is similar to or event better than that of cytology if stand alone HPV is used as primary screening test. Instead it decreases if HPV testing is used in combination with cytology as primary screening test and if all HPV positive women are referred to colposcopy. One RCT suggests relevant over-diagnosis of regressive CIN by HPV testing in women below age 35 years. Therefore stand-alone HPV testing for primary screening with cytological triage women aged 35 years or more seems an effective and safe screening strategy. In this situation it is needed to evaluate the applicability and sustainability of this approach in routine practice and its impact on costs, participation to screening. The objective is also to define the best organisation, define the best methods of communication with women, methods for quality control and indicators for process monitoring.
Ethics approval(s)	The ethics committee of University Hospital University Hospital San Giovanni Battista (Comitato Etico Interaziendale) approved on the 1st of February 2010 (ref: CEI/585)
Health condition(s) or problem(s) studied	Cervical cancer screening
Intervention	Intervention arm. Women will have two cervical samples taken, first one for a conventional cytological smear (by Ayres spatula and cytobrush) and one for HPV testing (by brush). Initially only the HPV test will be performed. The Hybrid Capture 2 (HC2) test, that is designed to detect the DNA of 13 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) will be applied. The cut-off of 1 RLU will be used as recommended by the manufacturer. Women negative to HC2 will be referred to a new screening round at standard interval. The cytological smears of women who test positive to HC2 will be stained and interpreted. Cytology will be interpreted according to the Bethesda 2001 system. If cytology is found to be Atypical Squamous Cells of Undetermined Significance (ASCUS) or more severe, women will be referred directly to colposcopy. The remaining HPV positive women will be re-invited after one year to repeat the HP test. At such repeat, women will be referred to colposcopy if the HPV test is positive, otherwise referred to the new screening round at standard interval. The standard interval for this group will be initially 3 years but could be changed to 5 years according to national guidelines. Colposcopies will be conducted according to standard protocols, as will treatments and repeats needed according to colposcopy and related histology and cytology results. Above this, women will be re-invited for new cytology and HPV test at yearly intervals until the HPV test will be negative for two consecutive tests. They will be referred to colposcopy if cytology is ASCUS or more severe. Control arm. Women will be tested by conventional cytology and managed according to the standard protocols of participating centres.
Intervention type	Other
Primary outcome measure	1. Compliance to invitation to screening 2. Proportion screened of women who test positive to HPV and cytology 3. Proportion of screened women referred to new tests 4. Referral rate to colposcopy 5. Compliance to referral to new tests and to colpscopy 6. Positive Predictive value of colposcopy 7. Detection rate of histologically confirmed high-grade lesions (CIN2+ and CIN3+)
Secondary outcome measures	1. Cost of each screening approach 2. Time needed to provide test results 3. Anxiety caused a positive test result
Overall study start date	22/03/2010
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	130,000
Key inclusion criteria	Women aged 35 to 64 years resident in the relevant areas.
Key exclusion criteria	1. Women previously enrolled in the NTCC trial (ISRCTN81678807) 2. Women unable to provide informed consent
Date of first enrolment	22/03/2010
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

Italy

Study participating centre

Via San Francesco da Paola 31

Torino
10123
Italy

Sponsor information

CPO Piemonte (Italy)
Research organisation

Via San Francesco da Paola 31
Torino
10123
Italy

Email	guglielmo.ronco@cpo.it
"ROR"	https://ror.org/05v0e5774

Funders

Funder type

Government

Italian Ministry of Health (Italy) - Costs of each screening methods will be partly covered by the funds locally allocated for routine screening.

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan