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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Precancerous Condition, Stage 0 Cervical Cancer

Intervention / Treatment
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* Other: Cervical Papanicolaou Test
* Procedure: Conization
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic<br>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: Cervical Papanicolaou Test<br>* Undergo Pap smear<br>* Other names: Cervical Pap Test;Procedure: Conization<br>* Undergo cone biopsy<br>* Other names: Conization of Uterine Cervix;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |