Strategies for Endocervical Canal Investigation in Women With Abnormal Screening Cytology and Negative Colposcopy

NCT05120167 | Completed

• 1 other identifier: 49006721.5.0000.5437
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 4

Brief Summary

cervical cancer is the fourth most frequent cancer in women worldwide and in Brazil, it occupies the third position for the triennium 2020/2022, with a high mortality rate and maintained in the last 10 years. It is associated with persistent human papillomavirus (HPV) infection. Primary prevention can be accomplished through vaccines that prevent HPV infection of the epithelial cells of the cervix. Secondary prevention in screening for precursor lesions through periodic repeat cervical sampling in a population of asymptomatic women. Women with abnormal cytology are more likely to have pre-invasive or invasive lesions and are referred for further testing, colposcopy. Colposcopy identifies suspicious areas and guides the best site for biopsy. In the situation of negative colposcopy and abnormal cytology, suspicion for high-grade lesion (HSIL). It recommends further investigation of the endocervical canal before the possible excisional procedure and obtaining an additional canal sample by brushing or curettage. However, to date, there is no consensus and studies lack consistent results on which is the best method for further investigation of the endocervix. Objectives: To compare the performance of additional strategies in the investigation and detection of precursor or invasive lesions in the endocervical canal in women with abnormal cytology (ASC H+) and with initial colposcopy without suspicious images.

Conditions

Diagnoses Disease; Screening; HSIL of Cervix; Cervical Cancer

Keywords

Diagnostic Methods; Additional Endocervical Brushing; Endocervical canal curettage; Screening and Prevention Cervical Cancer; Precancer lesion

Outcome Measures

Primary Outcomes (3)

• Acuracy of endocervical cytology sample preserved in a liquid-based in the evaluation of the endocervical canal

  calculation sensitivity (SENS), specificity (SPEC), negative predictive value (NPV) and positive predictive value (PPV) of cytology in the diagnosis of pre-invasive and invasive cervical lesion, considering histology as the gold standard or 12-month follow-up.

  12 months

• Acuracy of endocervical cell block sample preserved in a buffered formalin base in the evaluation of the endocervical canal

  calculation sensitivity (SENS), specificity (SPEC), negative predictive value (NPV) and positive predictive value (PPV) of endocervical cell block in the diagnosis of pre-invasive and invasive cervical lesion, considering histology as the gold standard or 12-month follow-up.

  12 months

• Acuracy of endocervical curettage sample preserved in a buffered formalin base in the evaluation of the endocervical canal

  calculation sensitivity (SENS), specificity (SPEC), negative predictive value (NPV) and positive predictive value (PPV) of endocervical curettage in the diagnosis of pre-invasive and invasive cervical lesion, considering histology as the gold standard or 12-month follow-up.

  12 months

Study Arms (3)

Endocervical cytology performed by liquid-based cytology

ACTIVE COMPARATOR

Endocervical sample collected by brushing and preserved in a liquid base, and evaluated as cytology.

Diagnostic Test: Endocervical liquid-base cytology

Endocervical cell block from a canal sample preserved in a buffered formalin base

ACTIVE COMPARATOR

Endocervical sample collected by brushing and preserved in a buffered formalin base for obtaining a "cell block", and evaluated similarly as histology.

Diagnostic Test: Endocervical cell block

Endocervical curettage

ACTIVE COMPARATOR

Endocervical curettage sample preserved in buffered formalin and evaluated by histology.

Diagnostic Test: Endocervical curettage

Interventions

Endocervical liquid-base cytology DIAGNOSTIC_TEST

Endocervical sample collected by brushing and preserved in a liquid-base.

Endocervical cytology performed by liquid-based cytology

Endocervical cell block DIAGNOSTIC_TEST

Endocervical sample collected by endocervical brush and preserved in a buffered formalin base for obtaining a "cell block" and evaluated as histology.

Endocervical cell block from a canal sample preserved in a buffered formalin base

Endocervical curettage DIAGNOSTIC_TEST

Endocervical sample obtained by curettage, preserved in buffered formalin, and evaluated as histology.

Endocervical curettage

Eligibility Criteria

• Age: 25 Years+
• Gender Eligibility Details: Women with abnormal cytology of the uterine cervix in the cervical cancer screening program
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women aged 25 years or older with altered cytology (ASC-H+) and attended the care unit and who consented to participate in the study by signing the Informed Consent Form
• Non-pregnant

You may not qualify if:

• colposcopy with abnormal findings;
• total hysterectomy (extirpation of the cervix);
• cervical stenosis or imperviousness near the external orifice.

Sponsors & Collaborators

• Cirbia Silva Campos Teixeira: lead

Study Sites (4)

Hospital de Cancer de Barretos

Campo Grande, Mato Grosso do Sul, 79085040, Brazil

Location

Sandra Moretti Jusselino Maniçoba Palopoli

Nova Andradina, Mato Grosso do Sul, 79750000, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784400, Brazil

Location

Hospital de Cancer de Barretos

Campinas, São Paulo, 13036225, Brazil

Location

Related Publications (16)

• Lei J, Ploner A, Elfstrom KM, Wang J, Roth A, Fang F, Sundstrom K, Dillner J, Sparen P. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020 Oct 1;383(14):1340-1348. doi: 10.1056/NEJMoa1917338.

  PMID: 32997908 BACKGROUND

• Possati-Resende JC, Fregnani JH, Kerr LM, Mauad EC, Longatto-Filho A, Scapulatempo-Neto C. The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL. PLoS One. 2015 Jul 31;10(7):e0134445. doi: 10.1371/journal.pone.0134445. eCollection 2015.

  PMID: 26230097 BACKGROUND

• Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12-9. doi: 10.1002/(SICI)1096-9896(199909)189:13.0.CO;2-F.

  PMID: 10451482 BACKGROUND

• Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003 Jan;16(1):1-17. doi: 10.1128/CMR.16.1.1-17.2003.

  PMID: 12525422 BACKGROUND

• Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, Clifford GM. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer. 2007 Aug 1;121(3):621-32. doi: 10.1002/ijc.22527.

  PMID: 17405118 BACKGROUND

• Munoz N, Bosch FX, Castellsague X, Diaz M, de Sanjose S, Hammouda D, Shah KV, Meijer CJ. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004 Aug 20;111(2):278-85. doi: 10.1002/ijc.20244.

  PMID: 15197783 BACKGROUND

• Zeferino LC, Derchain SF. Cervical cancer in the developing world. Best Pract Res Clin Obstet Gynaecol. 2006 Jun;20(3):339-54. doi: 10.1016/j.bpobgyn.2006.01.018. Epub 2006 Mar 24.

  PMID: 16563869 BACKGROUND

• Kjaer SK, van den Brule AJ, Paull G, Svare EI, Sherman ME, Thomsen BL, Suntum M, Bock JE, Poll PA, Meijer CJ. Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ. 2002 Sep 14;325(7364):572. doi: 10.1136/bmj.325.7364.572.

  PMID: 12228133 BACKGROUND

• Hall MT, Simms KT, Lew JB, Smith MA, Brotherton JM, Saville M, Frazer IH, Canfell K. The projected timeframe until cervical cancer elimination in Australia: a modelling study. Lancet Public Health. 2019 Jan;4(1):e19-e27. doi: 10.1016/S2468-2667(18)30183-X. Epub 2018 Oct 2.

  PMID: 30291040 BACKGROUND

• Derchain S, Teixeira JC, Zeferino LC. Organized, Population-based Cervical Cancer Screening Program: It Would Be a Good Time for Brazil Now. Rev Bras Ginecol Obstet. 2016 Apr;38(4):161-3. doi: 10.1055/s-0036-1582399. Epub 2016 Apr 18. No abstract available.

  PMID: 27088706 BACKGROUND

• El-Zein M, Gotlieb W, Gilbert L, Hemmings R, Behr MA, Franco EL; STAIN-IT Study Group. Dual staining for p16/Ki-67 to detect high-grade cervical lesions: Results from the Screening Triage Ascertaining Intraepithelial Neoplasia by Immunostain Testing study. Int J Cancer. 2021 Jan 15;148(2):492-501. doi: 10.1002/ijc.33250. Epub 2020 Aug 24.

  PMID: 32781481 BACKGROUND

• Fonseca FV, Tomasich FD, Jung JE, Maestri CA, Carvalho NS. The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment. Rev Col Bras Cir. 2016 Feb;43(1):35-41. doi: 10.1590/0100-69912016001008. English, Portuguese.

  PMID: 27096855 BACKGROUND

• Waxman AG, Chelmow D, Darragh TM, Lawson H, Moscicki AB. Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix. Obstet Gynecol. 2012 Dec;120(6):1465-71. doi: 10.1097/aog.0b013e31827001d5.

  PMID: 23168774 BACKGROUND

• Goksedef BP, Api M, Kaya O, Gorgen H, Tarlaci A, Cetin A. Diagnostic accuracy of two endocervical sampling method: randomized controlled trial. Arch Gynecol Obstet. 2013 Jan;287(1):117-22. doi: 10.1007/s00404-012-2542-9. Epub 2012 Sep 5.

  PMID: 22948805 BACKGROUND

• Tuon FF, Bittencourt MS, Panichi MA, Pinto AP. [Sensibility and specificity of cytology and colposcopy exams with the histological evaluation of cervical intraepithelial lesions]. Rev Assoc Med Bras (1992). 2002 Apr-Jun;48(2):140-4. doi: 10.1590/s0104-42302002000200033. Portuguese.

  PMID: 12205531 BACKGROUND

• Undurraga M, Catarino R, Navarria I, Ibrahim Y, Puget E, Royannez Drevard I, Pache JC, Tille JC, Petignat P. User perception of endocervical sampling: A randomized comparison of endocervical evaluation with the curette vs cytobrush. PLoS One. 2017 Nov 6;12(11):e0186812. doi: 10.1371/journal.pone.0186812. eCollection 2017.

  PMID: 29107949 BACKGROUND

Related Links

• Organization WH. International Agency for Reseach on Cancer. Cervix uteri Source: Globocan 2020. Internet, 2020.
• Brasil. Ministério da Saúde. Instituto Nacional de Câncer. Estimativa para 2020-22 do câncer do colo uterino no Brasil e diferentes regiões, 2020.
• ABPTGIC. Associação Brasileira de Patologia do Trato Genital Inferior e Colposcopia. Novas estratégias para o rastreamento cervical baseadas no teste para hpv, 2021.
• FEBRASGO. Federação Brasileira das Associações de Ginecologia e Obstetrícia Internet. Rastreamento para câncer de colo uterino: o que há de novo?, 2020.
• Brasil. Ministério da Saúde. Instituto Nacional de Câncer. Diretrizes para o rastreamento do Câncer do Colo do útero. Rio de Janeiro: INCA, 2016, 2016.
• ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Scre- ening Tests and Cancer Precursors. J Low Genit Tract Dis., 24:102 - 131, 2020.
• Miranda W, Miziara F, Saieg M, and Fronza H. Atualização Nomeclatura Brasileira para Laudos citopatológicos do colo uterino e Ano-Gentiais. Sociedade Brasileira de Citopatologia. 2020.
• Organization WH. International Agency for Reseach on Cancer. Citopatologia do colo uterino - atlas digital: Sistema Bethesda de 2001. Internet, 2001.
• Brasil. Ministério da Saúde. Instituto Nacional de Câncer. Resolução CNS 466/12.

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Cirbia SC Teixeira, MD

  Hospital de Cancer de Barretos

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Doctor

Model Details: Study design Clinical, randomized, controlled trial to evaluate the performance of tests for diagnosing precursor and invasive lesions in the endocervical canal.

Study Record Dates

• First Submitted: October 17, 2021
• First Posted: November 15, 2021
• Study Start: September 29, 2021
• Primary Completion: September 29, 2022
• Study Completion: November 30, 2022
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (4)