CA-IX, p16, Proliferative Markers, and HPV in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells

PRIMARY OBJECTIVES:

I. To examine CA-IX, p16, Ki-67, and mini-chromosome maintenance complex component 2 (MCM2)
expression in liquid-based cytology (LBC) specimens to see which subset of markers can
provide the optimal diagnosis of significant cervical lesions in women in North America with
a cytologic diagnosis of atypical glandular cells (AGC) and a positive test for high risk
human papillomavirus (HPV).

II. To examine high risk HPV, CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens to see
which subset of markers can provide the optimal diagnosis of significant cervical lesions in
women in Japan and Korea (with each country?s cohort analyzed separately) with a cytologic
diagnosis of AGC.

SECONDARY OBJECTIVES:

I. To determine whether the accuracy of diagnosis based on high risk HPV and expression of
CA-IX, p16, Ki-67, and/or MCM2 varies with patient age at enrollment and country of
enrollment.

TERTIARY OBJECTIVES:

I. To assess biomarker expression, loss of heterozygosity, and chromosome gains/losses in
formalin-fixed, paraffin-embedded tissue from the highest grade or most abnormal lesion in
women from North America, Japan, or Korea presenting with a cytologic diagnosis of AGC or
with a cytologic/histologic diagnosis of adenocarcinoma in situ (AIS).

II. To determine CA-IX, p16, Ki67, and MCM2 expression in LBC specimens to see which subset
(or combination) of markers will provide higher sensitivity in the diagnosis of cervical
adenocarcinoma in situ (AIS).

OUTLINE:

Patients undergo liquid-based cytology specimen sample collection for analysis of CA-IX, p16,
Ki-67, and MCM2 expression via immunohistochemistry (IHC) and for the presence of high risk
HPV deoxyribonucleic acid (DNA) and HPV genotyping.

Inclusion Criteria:

- Patients with a cytologic diagnosis of AGC (AGC, atypical endocervical cells [AEC],
atypical endometrial cells [AEmC]) or a cytologic/histologic diagnosis of AIS
documented within the last 6 months who can wait at least one week after the AGC or
AIS diagnosis to have an LBC specimen (i.e., ThinPrep) collected and then receive any
other intervention; acceptable time frame range is 4 days prior to registration to 7
days after registration

- Patients with positive HPV results who are willing to undergo a complete histologic
examination of the uterus and cervix, including the cervical transformation zone,
within 6 months of the AGC or AIS diagnosis (histologic examination includes a loop
electrosurgical excision procedure [LEEP], loop excision of the transformation zone
[LETZ], excisional cone biopsy, or hysterectomy)

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

Exclusion Criteria:

- Patients who have had a hysterectomy

- History of endometrial hyperplasia or cancer of the endometrium, vagina, or cervix

- Patients who have previously been treated, or are currently being treated with
radiation therapy or chemotherapy for vaginal or cervical cancer

- Patients who are known to be human immunodeficiency virus (HIV)-positive

- Patients who are pregnant and thought to be at risk for excessive bleeding or preterm
labor if a cone biopsy is performed