Conservative Management of HSIL in Patients With Future Pregnancy Aspiration

NCT04783805 | Recruiting

• 1 other identifier: IIBSP-CIN-2020-126
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Conservative management of high-grade squamous intraepithelial lesions (HSILs) seems safe and justified in young women (\<30 years), but evidence is insufficient on whether it is also advisable for older women. This study will be conducted to analyze spontaneous HSIL regression rates in women of reproductive age and establish whether conservative HSIL management could be safely recommended to women of childbearing potential, irrespective of age. This is a single-center prospective observational study that will include consecutive women of reproductive age, referred to a tertiary hospital due to HSIL between March 2021 and December 2025, who prefer conservative management rather than immediate cervical conization. All patients will be followed-up regularly with colposcopy, cytology, human papillomavirus (HPV) testing and biopsies. In case their lesions progress or HSIL persists after 24 months of follow-up, conization will be indicated. Rates of spontaneous regression or resolution, as well as progression rates, will be assessed. Furthermore, the association between potential predictive factors and HSIL resolution will be analyzed.

Conditions

Cervical Intraepithelial Neoplasia; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Dysplasia

Keywords

H-SIL; Conservative management; CIN

Outcome Measures

Primary Outcomes (4)

• HSIL regression

  Abscence of colposcopic lesion or regression of colposcopic lesion

  2 years

• Cytology

  normal, LSIL or ASCUS

  2 years

• Biopsy

  normal, LSIL or ASCUS

  2 years

• VPH

  negative HPV for the HPV type initially detected

  2 years

Study Arms (2)

Spontaneous HSIL regression

Patients that have spontaneous regression of HSIL throughout follow-up. Patients in this group will be further classified into 3 subgroups: total resolution (no colposcopic lesion, normal pathology by biopsy and cytology, and negative HPV for the HPV type initially detected); partial resolution (regression of colposcopic lesion, negative cytology and biopsies, but persistence of the initial hrHPV detected); and lesion regression (HSIL no longer detected, but persistent LSIL in either cytology, histology or colposcopy).

Diagnostic Test: Conservative management with regular follow-up

Conization

Women who have cervical conization for any reason during follow-up. Patients in this group will be further classified according to indication criteria: failure to meet criteria for conservative management or persistence of HSIL after 24 months of follow-up.

Procedure: Conization

Interventions

Conservative management with regular follow-up DIAGNOSTIC_TEST

Women will be followed-up every 4 months, with colposcopy and cytology at each visit.

Spontaneous HSIL regression

Conization PROCEDURE

Women with progression of HSIL, HSIL persistence after 24 months of follow-up, or that no longer meet the criteria for surveillance will have conization

Conization

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women referred to the PTGI Unit of a tertiary hospital (Hospital de la Santa Creu i Sant Pau, Barcelona, Spain) with a biopsy-confirmed histological diagnosis of HSIL (CIN2 or CIN3) from February 2021 to December 2025, who meet the inclusion criteria and have freely decided on conservative management, with a minimum follow-up of 2 years and maximum 7.

You may qualify if:

• Reproductive age and aspirations of future pregnancies
• Acceptance of conservative management
• Commitment to attend scheduled follow-up visits
• Colposcopy with transformation zone (ZT) type 1 or 2 (fully visible squamous-columnar union) with lesion with grade 2 changes visible in its entirety. No endocervical involvement
• Colposcopy with grade 2 changes that are not extensive: \<50% of the cervical surface

You may not qualify if:

• Pregnancy at first visit or during follow-up.
• Immunosuppression (either iatrogenic or due to human immunodeficiency virus (HIV))
• Suspected or diagnosed Atypical Glandular Cells (ACG), In Situ Adenocarcinoma (AIS) or Cervical Cancer (CC)

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead

Study Sites (1)

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Related Publications (8)

• Tainio K, Athanasiou A, Tikkinen KAO, Aaltonen R, Cardenas J, Hernandes, Glazer-Livson S, Jakobsson M, Joronen K, Kiviharju M, Louvanto K, Oksjoki S, Tahtinen R, Virtanen S, Nieminen P, Kyrgiou M, Kalliala I. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018 Feb 27;360:k499. doi: 10.1136/bmj.k499.

  PMID: 29487049 BACKGROUND

• Discacciati MG, de Souza CA, d'Otavianno MG, Angelo-Andrade LA, Westin MC, Rabelo-Santos SH, Zeferino LC. Outcome of expectant management of cervical intraepithelial neoplasia grade 2 in women followed for 12 months. Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):204-8. doi: 10.1016/j.ejogrb.2010.12.002. Epub 2010 Dec 28.

  PMID: 21193261 BACKGROUND

• Ho GY, Einstein MH, Romney SL, Kadish AS, Abadi M, Mikhail M, Basu J, Thysen B, Reimers L, Palan PR, Trim S, Soroudi N, Burk RD; Albert Einstein Cervix Dysplasia Clinical Consortium. Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting. J Low Genit Tract Dis. 2011 Oct;15(4):268-75. doi: 10.1097/LGT.0b013e3182216fef.

  PMID: 21811178 BACKGROUND

• McAllum B, Sykes PH, Sadler L, Macnab H, Simcock BJ, Mekhail AK. Is the treatment of CIN 2 always necessary in women under 25 years old? Am J Obstet Gynecol. 2011 Nov;205(5):478.e1-7. doi: 10.1016/j.ajog.2011.06.069. Epub 2011 Jun 25.

  PMID: 21872201 BACKGROUND

• McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008 May;9(5):425-34. doi: 10.1016/S1470-2045(08)70103-7. Epub 2008 Apr 11.

  PMID: 18407790 BACKGROUND

• Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006 Feb 11;367(9509):489-98. doi: 10.1016/S0140-6736(06)68181-6.

  PMID: 16473126 BACKGROUND

• Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P, Arbyn M, Bennett P, Paraskevaidis E. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ. 2016 Jul 28;354:i3633. doi: 10.1136/bmj.i3633.

  PMID: 27469988 BACKGROUND

• Kyrgiou M, Athanasiou A, Kalliala IEJ, Paraskevaidi M, Mitra A, Martin-Hirsch PP, Arbyn M, Bennett P, Paraskevaidis E. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst Rev. 2017 Nov 2;11(11):CD012847. doi: 10.1002/14651858.CD012847.

  PMID: 29095502 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Squamous Intraepithelial Lesions of the Cervix

Interventions

Conization

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Squamous Intraepithelial Lesions; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Cristina Vanrell Barbat, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  STUDY DIRECTOR

• Nerea Nerea

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalia Teixeira, MD, Ph.D.

CONTACT

+34604311873; nteixeira@santpau.cat

Nerea Nerea, MD

CONTACT

+34935537041; nluqui@santpau.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 5, 2021
• Study Start: March 3, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 5, 2021

Record last verified: 2021-03

Locations

ES (1)