Protein Expression as a Potential Diagnostic Biomarker of Cervical Dysplasia and/or Cancer

Expression of the MN Protein in Atypical Glandular Cells of Undetermined Significance (Agus or Agcus) As a Potential Diagnostic Biomarker of Cervical Dysplasia/Neoplasia

This diagnostic trial is studying the presence of a specific protein as a potential biomarker of cervical dysplasia and/or cancer. The presence of specific proteins may allow a doctor to determine whether a patient has cervical dysplasia and/or cancer.

Study Overview

• Status: Completed
• Conditions: Precancerous Condition; Stage 0 Cervical Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Cervical Papanicolaou Test; Procedure: Conization

Detailed Description

OBJECTIVES:

I. Evaluate the utility of MN protein, a novel tumor-associated antigen, as a potential diagnostic biomarker for cervical glandular and/or squamous neoplasia in patients with a cytologic diagnosis of atypical glandular cells of undetermined significance (AGUS).

II. Measure the frequency and type of cervical pathology associated with the diagnosis of AGUS in these patients.

III. Determine whether the presence of a high-risk type of human papilloma virus (HPV) in a ThinPrep cervical cell specimen predicts the presence of cervical glandular and/or squamous cell neoplasia in these patients.

IV. Determine the relationship between MN antigen expression and the presence of high-risk HPV in these patients.

OUTLINE: This is a multicenter study.

Patients undergo a Pap smear followed by a ThinPrep cervical cell specimen collection at the time of direct colposcopic examination. Patients then undergo a cone biopsy of the cervix using loop electrosurgical excision procedure with an endocervical curettage, an excisional cone biopsy of the cervix with or without endocervical curettage, or a hysterectomy. Patients who are perimenopausal or postmenopausal or have a negative cervical cone biopsy also undergo endometrial biopsy or curettage. The Pap smear specimen is analyzed to determine MN antigen expression and the ThinPrep specimen is analyzed for the presence of high-risk human papilloma virus and to determine MN antigen and other marker (e.g., P16) expression.

Patients who do not undergo hysterectomy are followed every 6 months for 2 years. All other patients are followed at 4, 26, and 30 weeks.

• Study Type: Interventional
• Enrollment (Actual): 684
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Gynecologic Oncology Group of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Cytologically confirmed atypical glandular cells of undetermined significance (AGUS)
• Must be scheduled to undergo complete histologic examination of the cervix by cone biopsy using loop electrosurgical excision procedure with an endocervical curettage, excisional cone biopsy with or without endocervical curettage, or hysterectomy within 6 months of the initial cytologic diagnosis of AGUS
• No history of endometrial hyperplasia
• No history of cancer of the endometrium, vagina, or cervix
• HIV negative
• No pregnant patients who are at high risk for excessive bleeding or preterm labor if a cone biopsy is performed
• No prior cytotoxic chemotherapy for vaginal and/or cervical cancer
• No prior radiotherapy to the vagina or cervix
• No concurrent radiotherapy to the vagina or cervix
• No prior hysterectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Diagnostic; Patients undergo a Pap smear followed by a ThinPrep cervical cell specimen collection at the time of direct colposcopic examination. Patients then undergo a cone biopsy of the cervix using loop electrosurgical excision procedure with an endocervical curettage, an excisional cone biopsy of the cervix with or without endocervical curettage, or a hysterectomy. Patients who are perimenopausal or postmenopausal or have a negative cervical cone biopsy also undergo endometrial biopsy or curettage. The Pap smear specimen is analyzed to determine MN antigen expression and the ThinPrep specimen is analyzed for the presence of high-risk human papilloma virus and to determine MN antigen and other marker (e.g., P16) expression. Patients who do not undergo hysterectomy are followed every 6 months for 2 years. All other patients are followed at 4, 26, and 30 weeks.

Other: Laboratory Biomarker Analysis; Correlative studies; Other: Cervical Papanicolaou Test; Undergo Pap smear; Other Names: Cervical Pap Test; Procedure: Conization; Undergo cone biopsy; Other Names: cone biopsy; Cone Biopsy of Cervix; Conization of Cervix; Conization of Uterine Cervix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Expression of the MN antigen in cytologic preparations that have been classified as AGUS	Baseline
Number of cervical specimens identified as having or not having glandular and/or squamous neoplasia	Baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Ability of the MN antigen marker to be able to correctly predict patients who do not have glandular and/or squamous neoplasia	Up to 2 years
Feasibility, based on the number of years required to complete the study, as determined by both the actual disease prevalence rate as well as the actual patient accrual rate	At 1 year
Sensitivity for HIV testing	Baseline
Sensitivity of the expression of the MN antigen	Baseline
Specificity for HIV testing	Baseline
Specificity of the expression of the MN antigen	Baseline

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): May 29, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Precancerous Conditions; Uterine Cervical Dysplasia
• Other Study ID Numbers: GOG-171 (OTHER: Gynecologic Oncology Group); NCI-2012-02269 (REGISTRY: CTRP (Clinical Trial Reporting Program)); CDR0000066380; GOG-0171 (OTHER: CTEP)