Algorithm for Cervix Carcinoma Screening in CZ Using the Detection of HPV DNA and CINtec Plus

NCT ID: NCT05578833

Last Updated: 2022-10-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

2426 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-01

Study Completion Date

2021-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Cervix carcinoma has been a serious, long-term issue in the Czech Republic. The cause of nearly all cervix carcinomas is human papilomavirus (HPV). Hence the detection of the HPV genome is a more prospective screening tool with higher sensitivity than a cytological swab. As shown by comparative studies, the sensitivity of the HPV DNA test in the detection of severe pre-cancer is 35% higher on average when compared to the cytological test.

The study repeatedly determined the presence of the HPV genome, including the prevalence of selected HPV genotypes (16, 18 and other hrHPV) and conventional cytology. The relative sensitivity of the two methods was specified. In the course of the prospective follow-up, the incidence of pre-cancers and invasive tumours in the study population were specified.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Cervix carcinoma has been a serious, long-term issue in the Czech Republic. About 1,000 new cases are diagnosed every year and about 400 female patients die as a result of the disease. More than 20,000 women in the Czech Republic live with a history of cervix carcinoma therapy and the potential risk of its recurrence. Although the past years have been marked with effective organisational changes in cervix carcinoma screening thanks to which a decreasing trend of its incidence can be observed, there is a lack of substantial impact on the occurrence of advanced stages of the disease and mortality. Similar data have also been reported internationally: foreign authors analysed cases of patients with a malignant cervix tumour. They reported that 24 - 32% of females with a diagnosed malignant tumour had periodically undergone cytological screening. The reason is that the sensitivity of an individual cytological examination for detecting severe pre-cancer is limited, ranging between 40 - 75% and only increasing with repeated examinations. The negative predictive value of the cytological swab is additionally limited and reaches 0.78% in recent studies over a three-year screening interval.

The cause of nearly all cervix carcinomas is human papilomavirus (HPV). Hence the detection of the HPV genome is a more prospective screening tool with higher sensitivity than a cytological swab. The sensitivity of the validated HPV DNA test using PCR method reaches 94.5% for detecting severe pre-cancer (confidence interval 94.2 - 96.9%). As shown by comparative studies, the sensitivity of the HPV DNA test for the detection of severe pre-cancer is 35% higher on average when compared to the cytological test. The HPV DNA test in addition shows a significantly better negative three-year predictive value (0.34%) and the low value continues for at least another five years. The lower specificity of the HPV DNA test can be compensated by selective genotype specification with proof of the most frequent oncogenic genotypes HPV 16 and HPV 18. This promising procedure, validated by large multicentric randomised studies and introduced to clinical practice in several European countries, primarily uses the detection of HPV DNA.

The study repeatedly determined the presence of the HPV genome, including the prevalence of selected HPV genotypes (16, 18 and other hrHPV) and conventional cytology. The relative sensitivity of the two methods was specified. In the course of the prospective follow-up, the incidence of pre-cancers and invasive tumours in the study population were specified.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Algorithm for Cervix Carcinoma Screening

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_CROSSOVER

Study Time Perspective

PROSPECTIVE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

HPV DNA test with selective HPV 16/18 genotyping (cobas® 4800 HPV Test, Roche)

The enrolled patients underwent standard conventional cytology plus a test for the detection of high-risk human papilomavirus (hrHPV) with selective genotype specification (HPV 16, 18 and other hrHPV) - combined screening. In defined cases of positive hrHPV, the patient underwent reflexive examination by CINtec plus technology.

After the initial combined screening the patients continued in the standard Czech screening practice (annual conventional cytology) or be treated according to the particular finding of the initial episode. For three years, the incidence of pre-cancers and invasive cervix carcinomas were monitored and data were entered into an electronic register.

The second combined screening episode followed in year 3. An evaluation of its results immediately followed.

Intervention Type DIAGNOSTIC_TEST

p16 and Ki-67 biomarker detection in the form of dual cytological staining (CINtec Plus, Roche)

The enrolled patients underwent standard conventional cytology plus a test for the detection of high-risk human papilomavirus (hrHPV) with selective genotype specification (HPV 16, 18 and other hrHPV) - combined screening. In defined cases of positive hrHPV, the patient underwent reflexive examination by CINtec plus technology.

After the initial combined screening the patients continued in the standard Czech screening practice (annual conventional cytology) or be treated according to the particular finding of the initial episode. For three years, the incidence of pre-cancers and invasive cervix carcinomas were monitored and data were entered into an electronic register.

The second combined screening episode followed in year 3. An evaluation of its results immediately followed.

Intervention Type DIAGNOSTIC_TEST

standard conventional cytology PAP test

The enrolled patients underwent standard conventional cytology plus a test for the detection of high-risk human papilomavirus (hrHPV) with selective genotype specification (HPV 16, 18 and other hrHPV) - combined screening. In defined cases of positive hrHPV, the patient underwent reflexive examination by CINtec plus technology.

After the initial combined screening the patients continued in the standard Czech screening practice (annual conventional cytology) or be treated according to the particular finding of the initial episode. For three years, the incidence of pre-cancers and invasive cervix carcinomas were monitored and data were entered into an electronic register.

The second combined screening episode followed in year 3. An evaluation of its results immediately followed.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Informed consent signature
* Age 30 - 60
* Screening (not reviewing after previous abnormal cytological finding)
* Sampling of gravid women possible

Exclusion Criteria

* Refusal to take part
Minimum Eligible Age

30 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Institute of Biostatistics and analyses, Ltd.

UNKNOWN

Sponsor Role collaborator

AeskuLab Pathology Prague

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Markéta Trnková, MD

Role: PRINCIPAL_INVESTIGATOR

Aeskulab Patologie, ks

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Aeskulab Patologie, ks

Prague, Czech Republic, Czechia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Czechia

References

Explore related publications, articles, or registry entries linked to this study.

Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M, Scott DR, Rush BB, Glass AG, Schiffman M. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005 Jul 20;97(14):1072-9. doi: 10.1093/jnci/dji187.

Reference Type BACKGROUND
PMID: 16030305 (View on PubMed)

Kjaer SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010 Oct 6;102(19):1478-88. doi: 10.1093/jnci/djq356. Epub 2010 Sep 14.

Reference Type BACKGROUND
PMID: 20841605 (View on PubMed)

McMenamin M, McKenna M, McDowell A. Clinical Utility of CINtec PLUS Triage in Equivocal Cervical Cytology and Human Papillomavirus Primary Screening. Am J Clin Pathol. 2018 Oct 24;150(6):512-521. doi: 10.1093/ajcp/aqy073.

Reference Type BACKGROUND
PMID: 30169728 (View on PubMed)

Meijer CJ, Berkhof J, Castle PE, Hesselink AT, Franco EL, Ronco G, Arbyn M, Bosch FX, Cuzick J, Dillner J, Heideman DA, Snijders PJ. Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older. Int J Cancer. 2009 Feb 1;124(3):516-20. doi: 10.1002/ijc.24010.

Reference Type BACKGROUND
PMID: 18973271 (View on PubMed)

Petry KU, Schmidt D, Scherbring S, Luyten A, Reinecke-Luthge A, Bergeron C, Kommoss F, Loning T, Ordi J, Regauer S, Ridder R. Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology. Gynecol Oncol. 2011 Jun 1;121(3):505-9. doi: 10.1016/j.ygyno.2011.02.033. Epub 2011 Mar 21.

Reference Type BACKGROUND
PMID: 21420158 (View on PubMed)

Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA, Kenter GG, Cuzick J, Snijders PJ, Meijer CJ. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012 Jan;13(1):78-88. doi: 10.1016/S1470-2045(11)70296-0. Epub 2011 Dec 14.

Reference Type BACKGROUND
PMID: 22177579 (View on PubMed)

Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, Kitchener H, Segnan N, Gilham C, Giorgi-Rossi P, Berkhof J, Peto J, Meijer CJ; International HPV screening working group. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet. 2014 Feb 8;383(9916):524-32. doi: 10.1016/S0140-6736(13)62218-7. Epub 2013 Nov 3.

Reference Type BACKGROUND
PMID: 24192252 (View on PubMed)

Sehnal B, Slama J. What next in cervical cancer screening? Ceska Gynekol. 2020 Winter;85(4):236-243.

Reference Type BACKGROUND
PMID: 33562978 (View on PubMed)

Sheikh S, Biundo E, Courcier S, Damm O, Launay O, Maes E, Marcos C, Matthews S, Meijer C, Poscia A, Postma M, Saka O, Szucs T, Begg N. A report on the status of vaccination in Europe. Vaccine. 2018 Aug 9;36(33):4979-4992. doi: 10.1016/j.vaccine.2018.06.044. Epub 2018 Jul 4.

Reference Type BACKGROUND
PMID: 30037416 (View on PubMed)

Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Nov 15;155(10):687-97, W214-5. doi: 10.7326/0003-4819-155-10-201111150-00376. Epub 2011 Oct 17.

Reference Type BACKGROUND
PMID: 22006930 (View on PubMed)

Wright TC Jr, Behrens CM, Ranger-Moore J, Rehm S, Sharma A, Stoler MH, Ridder R. Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial. Gynecol Oncol. 2017 Jan;144(1):51-56. doi: 10.1016/j.ygyno.2016.10.031. Epub 2016 Oct 27.

Reference Type BACKGROUND
PMID: 28094038 (View on PubMed)

Hajjar DP, Marcus AJ, Etingin OR. Platelet-neutrophil-smooth muscle cell interactions: lipoxygenase-derived mono- and dihydroxy acids activate cholesteryl ester hydrolysis by the cyclic AMP dependent protein kinase cascade. Biochemistry. 1989 Oct 31;28(22):8885-91. doi: 10.1021/bi00448a030.

Reference Type BACKGROUND
PMID: 2557910 (View on PubMed)

Slama J, Dvorak V, Trnkova M, Skrivanek A, Hurdalkova K, Ovesna P, Novackova M. Importance of addition of HPV DNA testing to the cytology based cervical cancer screening and triage of findings with p16/Ki67 immunocytochemistry staining in 35 and 45 years old women LIBUSE trial data analysis. Ceska Gynekol. 2020 Winter;85(6):368-374.

Reference Type RESULT
PMID: 33711896 (View on PubMed)

Slama J, Dvorak V, Trnkova M, Skrivanek A, Hrabcova K, Ovesna P, Novackova M. Is phased implementation of HPV testing and triage with dual staining the way to transform organized cytology screening? Eur J Cancer Prev. 2024 Mar 1;33(2):168-176. doi: 10.1097/CEJ.0000000000000844. Epub 2023 Sep 21.

Reference Type DERIVED
PMID: 37751376 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

IBA1132

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.