p16 and Ki-67 Stainings and Natural Killer (NK) Cells in CIN-II Management

Cervical Cancer Clinical Trial

Official title:

Predictive Value of p16 and Ki-67 Immunohistochemical Staining and NK Cells in Expectant Management of Cervical Intraepithelial Neoplasia Grade 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02522585
• Other study ID #: CIN-II p16 NK
• Status: Completed
• Phase: N/A
• First received: August 7, 2015
• Last updated: April 19, 2016
• Start date: December 2011
• Est. completion date: December 2015

Study information

• Verified date: April 2016
• Source: Parc de Salut Mar
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Observational

Clinical Trial Summary

The objective of this study is to evaluate the outcome of cervical intraepithelial neoplasia grade 2 (CIN-II) patients followed up without treatment for 24 months according to p16 and ki-67 immunohistochemical staining and to the expression of NK cell receptors.

Description:

Cervical cancer and its precursor lesions, cervical intraepithelial neoplasia (CIN), represents a significant public health problem,induced by persistent infection of human papillomavirus (HPV). It is known that a significant percentage of CIN regresses spontaneously and only a minority of these lesions progress to cervical cancer. CIN-II is an intermediate state that can regress to CIN-I or less, or progress to CIN-III spontaneously. The rate of spontaneous regression and progression in follow-up studies are around 40-60% and 10-20%, respectively. Overestimating CIN-II lesions may cause overtreatment by excisional treatment and increase the risk of subsequent obstetric complications.

Patients newly diagnosed with CIN-II colposcopy-directed biopsy who agreed to follow up at four months intervals for at least 12 months with cervical cytology and colposcopy, were prospectively recruited. p16, ki-67 and NK receptors expression were analyzed in all CIN-II biopsies. Total regression, partial regression, persistence and progression rates of CIN-II were defined as a final outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• preferred expectant management than immediate treatment

• exocervical histological diagnosis of CIN-II

• lesion completely visualized by colposcopy

• entire squamocolumnar junction of the cervix was visible

• showing no evidence of any immunodeficiency disease

• no history of previous cervical treatment

• could be followed-up every four months during one year

• signed consent form

Exclusion Criteria:

• not coming to follow up appointments

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cervical Cancer
• Cervical Intraepithelial Neoplasia
• Uterine Cervical Neoplasms

Intervention

Other:
• Conservative management
Control of CIN-II with cytology and colposcopy to try to avoid unnecessary surgery

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Parc de Salut Mar

References & Publications (6)

del Pino M, Garcia S, Fusté V, Alonso I, Fusté P, Torné A, Ordi J. Value of p16(INK4a) as a marker of progression/regression in cervical intraepithelial neoplasia grade 1. Am J Obstet Gynecol. 2009 Nov;201(5):488.e1-7. doi: 10.1016/j.ajog.2009.05.046. Epub 2009 Aug 15. — View Citation

Discacciati MG, de Souza CA, d'Otavianno MG, Ângelo-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. — View Citation

Galgano MT, Castle PE, Atkins KA, Brix WK, Nassau SR, Stoler MH. Using biomarkers as objective standards in the diagnosis of cervical biopsies. Am J Surg Pathol. 2010 Aug;34(8):1077-87. doi: 10.1097/PAS.0b013e3181e8b2c4. — View Citation

Guedes AC, Brenna SM, Coelho SA, Martinez EZ, Syrjänen KJ, Zeferino LC. p16(INK4a) Expression does not predict the outcome of cervical intraepithelial neoplasia grade 2. Int J Gynecol Cancer. 2007 Sep-Oct;17(5):1099-103. Epub 2007 Mar 15. — View Citation

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. — View Citation

Tsoumpou I, Arbyn M, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P, Malamou-Mitsi V, Paraskevaidis E. p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 2009 May;35(3):210-20. doi: 10.1016/j.ctrv.2008.10.005. Epub 2009 Mar 3. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Status of cervix pathology using cervical smear test (CIN grade)	Cervical cytology test and colposcopy every 4 months starting with diagnose CIN-II or CIN-III means presence of lesion, CIN-I is regression of the lesion, and Negative is abscence of lesion.	2 years	No