Brief Summary
This research trial studies carbonic anhydrase 9 (CA-IX), p16, proliferative markers, and human papilloma virus (HPV) 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.
Brief Title
CA-IX, p16, Proliferative Markers, and HPV in Diagnosing Cervical Lesions in Patients With Abnormal Cervical Cells
Detailed Description
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.
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.
Completion Date
Completion Date Type
Estimated
Conditions
Atypical Endometrial Hyperplasia
Human Papillomavirus Infection
Stage 0 Cervical Cancer AJCC v7
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00892866
Org Class
Network
Org Full Name
GOG Foundation
Org Study Id
GOG-0237
Overall Status
Active, not recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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)
Primary Outcomes
Outcome Description
CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and receiver operating characteristic (ROC)-type analysis will be performed.
Outcome Measure
Biomarker expression in patients from North America
Outcome Time Frame
Baseline
Outcome Description
CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and ROC-type analysis will be performed.
Outcome Measure
Biomarker expression in patients from Japan
Outcome Time Frame
Baseline
Outcome Description
CA-IX, p16, Ki-67, and MCM2 expression in LBC specimens is measured via IHC. A logistic regression and ROC-type analysis will be performed.
Outcome Measure
Biomarker expression in patients from Korea
Outcome Time Frame
Baseline
Secondary Ids
Secondary Id
NCI-2009-01103
Secondary Id
CDR0000632236
Secondary Id
GOG-0237
Secondary Id
GOG-0237
Secondary Id
GOG-0237
Secondary Id
N01CM62201
Secondary Id
U10CA101165
Secondary Id
UG1CA189867
Secondary Outcomes
Outcome Description
Logistic regression analyses will be performed to assess the effect of age and country on sensitivity, specificity, false positive rate (FPR), and complement negative predictive value (NPVC.). For each country and at each age, an upper 95% confidence limit will be calculated for the NPVC.
Outcome Time Frame
Baseline
Outcome Measure
Effect of patient age on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression in the North American population
Outcome Description
Logistic regression analyses will be performed to assess the effect of age and country on sensitivity, specificity, FPR, and NPVC. For each country and at each age, an upper 95% confidence limit will be calculated for the NPVC.
Outcome Time Frame
Baseline
Outcome Measure
Effect of patient age on the accuracy of diagnosis based on CA-IX, HPV, p16, Ki-67, and/or MCM2 expression in the Korean and Japanese populations
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mark Einstein
Investigator Email
meinstei@montefiore.org
Investigator Phone