Trial Information

Observational - Comparative Analysis of CA-IX, p16, Proliferative Markers and Human Papilloma Virus (HPV) in the Diagnosis of Significant Cervical Lesions in Patients With a Cytologic Diagnosis of Atypical Glandular Cells (AGC)

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.