Studying Biomarkers in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells

• CA-IX , high-risk HPV, p16, Ki-67, and MCM2 expression in patients in North America [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  A logistic regression and ROC-type analysis will be performed.
• CA-IX , high-risk HPV, p16, Ki-67, and MCM2 expression in patients in Japan [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  A logistic regression and ROC-type analysis will be performed.

• CA-IX , high-risk HPV, p16, Ki-67, and MCM2 expression as an optimal diagnosis of cervical lesions in patients in North America [ Designated as safety issue: No ]
• CA-IX , high-risk HPV, p16, Ki-67, and MCM2 expression as an optimal diagnosis of cervical lesions in patients in Japan [ Designated as safety issue: No ]

• Effect of patient age and country (North America or Japan) on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Logistic regression analyses will be performed.
• Inter- and intra-reviewer reproducibility of scoring CA-IX, p16, Ki-67 and MCM2 biomarkers [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Logistic regression analyses will be performed.

• Effect of patient age and country (North America or Japan) on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression [ Designated as safety issue: No ]
• Inter- and intra-reviewer reproducibility of scoring CA-IX, p16, Ki-67 and MCM2 biomarkers [ Designated as safety issue: No ]

This clinical trial is studying biomarkers in diagnosing cervical lesions in patients with abnormal cervical cells. Studying biomarkers in abnormal cervical cells may improve the ability to find cervical lesions and plan effective treatment.

Study Subtype: Ancillary/Correlative Observational Study Model: Case-only Time Perspective: Retrospective Biospecimen Retention: Samples With DNA Biospecimen Description: Tissue Study Population Description: Primary care clinic Sampling Method: Non-Probability Sample

PRIMARY OBJECTIVES:

I. To examine the expression of CA-IX, high-risk human papilloma virus (HPV), p16, Ki-67, and MCM2 in liquid-based cytology (LBC) specimens to determine which subset of markers will provide the optimal diagnosis of significant cervical lesions in patients in North America with atypical glandular cells (AGC).

II. To examine the expression of CA-IX, high-risk HPV, p16, Ki-67, and MCM2 in LBC specimens to determine which subset of markers will provide the optimal diagnosis of significant cervical lesions in patients in Japan with AGC.

SECONDARY OBJECTIVES:

I. To determine whether the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression varies with patient age at study enrollment and country of enrollment (North American or Japan).

II. To assess the inter- and intra-reviewer reproducibility of scoring CA-IX, p16, Ki-67, and MCM2.

OUTLINE: This is a multicenter study.

Patients undergo a cone biopsy of the cervix by loop electrosurgical excision procedure (LEEP)* with or without endocervical curettage, an excisional cone biopsy* of the cervix with or without endocervical curettage, or a hysterectomy within 6 months after the initial cytologic diagnosis of atypical glandular cells (AGC). A complete histological examination of the cervix, including the transformation zone is performed.

NOTE: *Patients 35 years of age with negative cervical LEEP or excisional cone biopsy must undergo endometrial biopsy or curettage.

Liquid-based cytology specimens are collected within 1 week of study entry (prior to colposcopy examination and/or any surgical procedure). Specimens are analyzed for CA-IX, p16, Ki-67, and MCM2 expression by immunohistochemistry assays and for the presence of high-risk human papilloma virus (HPV) by Digene Hybrid Capture II HPV testing and Roche Linear Array HPV genotyping.

• Atypical Endocervical Glandular Cell of Undetermined Significance
• Atypical Endometrial Hyperplasia
• Atypical Glandular Cell of Undetermined Significance
• Cervical Cancer
• Cervical Intraepithelial Neoplasia Grade 2
• Cervical Intraepithelial Neoplasia Grade 3
• Human Papilloma Virus Infection

Inclusion Criteria:

• Cytologically confirmed atypical glandular cells (AGC), including any of the following types:

  • AGC of unclear cell origin
  • Atypical endocervical cells (AEC)
  • Atypical endometrial cells (AEmC)
• Must be able to wait ≥ 1 week after initial AGC diagnosis before beginning intervention
• No history of endometrial hyperplasia or cancer of the endometrium, vagina, or cervix
• No known HIV positivity
• Not pregnant
• Negative pregnancy test
• No prior hysterectomy
• No prior or concurrent radiotherapy or chemotherapy for vaginal or cervical cancer