Uterine Cervical Neoplasms, Uterine Cervical Cancer, Neoplasms, Squamous Cell, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Papilloma
Conditions
Keywords
Liquid based cytology, Surepath
Brief summary
This study will provide data on the performance of the BD SurePath Plus™ Pap test for identifying high grade cervical disease. This study will be conducted with approximately 12,500 women undergoing routine cervical cancer screening, of whom women with abnormal cytology and/or positive HPV test will be selected to undergo colposcopy and biopsy/ECC. Subjects with abnormal cytology results with biopsy results of less than or equal to CIN1 or CIN2 untreated will be asked to return in 6-8 months for follow-up testing. Subjects may be asked to proceed to a longer-term follow-up study and undergo cytological evaluation annually for 3 years (separate study).
Detailed description
This is a pivotal, multi-center in vitro diagnostic study comparing the BD SurePath Plus Pap test to current practice (cytologic examination utilizing the BD SurePath liquid-based Pap test with conjunctive HPV testing) for the detection of cervical cancer and high-grade cervical disease (collectively referred to as CIN2+) in women. The new BD SurePath Plus Pap Test combines a traditional Papanicolaou staining for cellular morphology, with brown nuclear immunostaining resulting from the over-expression of specific protein biomarkers, on one slide, to improve the detection of high-grade cervical disease and cervical cancer (collectively referred to as CIN2+).
Interventions
DEVICEBD SurePath Plus Pap test
BD SurePath Plus Pap test
DEVICEBD SurePath Pap test
BD SurePath Plus Pap test
PROCEDUREcolposcopy with biopsy/ECC
Colposcopy with biopsy/ECC for subjects with 1)BD SurePath Pap NILM, but HPV positive, or 2) BD SurePath Plus Pap test result of ASC-US or higher 3)BD SurePath Pap ASC-US or higher
DEVICEHPV DNA test
digene HC2 HPV DNA test
Sponsors
Becton, Dickinson and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Study subjects must give voluntary written informed consent to participate in this study. \- Females ages 18 - 35 years, inclusive; or women at high- risk for cervical cancer or its precursor lesions. High-risk is defined as: * Have had a previous high-risk HPV positive test in the last 5 years; or * Have had an abnormal Pap test (ASC-US or higher) in the last 5 years; or * Have not been screened for cervical cancer by either a Pap test or HPV test in the last 5 years.
Exclusion criteria
* Subjects who are 36 years of age or greater who are not high risk, and/or: 1. Have not had an abnormal Pap in the last 5 years; or 2. Have not had a positive HPV test in the last 5 years; or 3. Have been screened in the last 5 years without an abnormal Pap or HPV result * Subjects known to be pregnant or planning to become pregnant prior to the potential six months follow-up visit (self-reported). Subjects who decide to become pregnant prior to the six-month follow up visit or found to be pregnant after the first visit, but prior to the six-month follow-up visit will be terminated from further study participation at that time * Subjects who have had a prior complete or partial hysterectomy involving removal of the cervix. * Subjects who have had an application of chemical compounds to the cervical area within the 24 hours prior to study entry, e.g., acetic acid, iodine, spermicide, douche, anti-fungal medications, etc. * Subjects on whom conization, LEEP, laser surgery, or cryosurgery has been performed within the past five months. * Subjects currently undergoing radiation and/or chemotherapy. * Subjects under the age of 18. * Subjects who have previously received a HPV vaccine with any number of doses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | 10 months | Estimate the sensitivity, specificity, positive predictive value and negative predictive value of the BD SurePath Plus Pap test in detecting cervical disease as defined as CIN2 or higher |
Secondary
| Measure | Time frame |
|---|---|
| Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection. | 10 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Evaluable Participants All participants with satisfactory samples at completion of the study. | 3,731 |
| Total | 3,731 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | >36/Normal History | 50 |
| Overall Study | Age | 3 |
| Overall Study | HPV Vaccine after Enrollment | 17 |
| Overall Study | HPV Vaccine History | 28 |
| Overall Study | Hysterectomy | 2 |
| Overall Study | Hysterectomy post enrollment | 1 |
| Overall Study | Inclusion/Exclusion Violation | 3 |
| Overall Study | Incorrect Visit | 3 |
| Overall Study | Informed Consent Form Violation | 30 |
| Overall Study | Missing Sample | 9 |
| Overall Study | No Florida Lab License | 20 |
| Overall Study | Out of Window | 42 |
| Overall Study | Pregnancy | 88 |
| Overall Study | Sample Processing/Storage | 92 |
| Overall Study | Site Amendment prohibited colposcopy | 11 |
| Overall Study | Site/Subject non-compliance | 44 |
Baseline characteristics
| Characteristic | All Evaluable Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3731 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 889 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2842 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 3731 participants |
| Sex/Gender, Customized Female | 3731 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3,731 |
| other Total, other adverse events | 0 / 3,731 |
| serious Total, serious adverse events | 0 / 3,731 |
Outcome results
Primary
Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher
Estimate the sensitivity, specificity, positive predictive value and negative predictive value of the BD SurePath Plus Pap test in detecting cervical disease as defined as CIN2 or higher
Time frame: 10 months
Population: All evaluable non-missing samples.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (ASC-H+) | 23.2 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (ASC-US+) | 84.9 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (ASC-US+) | 84.7 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (ASC-US+) | 16.7 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (ASC-US+) | 99.4 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (ASC-H+) | 65.5 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (ASC-H+) | 92.2 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (ASC-H+) | 98.7 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (LSIL+) | 58.0 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (LSIL+) | 93.4 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (LSIL+) | 24.0 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (LSIL+) | 98.4 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (HSIL+) | 37.8 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (HSIL+) | 98.3 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (HSIL+) | 45.0 Percent |
| SurePath Plus | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (HSIL+) | 97.8 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (ASC-H+) | 97.9 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (HSIL+) | 97.1 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (LSIL+) | 97.8 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (ASC-US+) | 71.4 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (LSIL+) | 40.3 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (ASC-US+) | 88.7 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (HSIL+) | 99.8 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (ASC-US+) | 18.5 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (LSIL+) | 94.7 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | NPV (ASC-US+) | 98.9 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (HSIL+) | 16.0 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Sensitivity (ASC-H+) | 43.7 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (LSIL+) | 21.4 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | Specificity (ASC-H+) | 94.4 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (ASC-H+) | 21.8 Percent |
| SurePath Pap | Sensitivity, Specificity, PPV, and NPV of BD SurePath Plus Pap Test for the Determination of Cervical Disease as Defined by CIN2 or Higher | PPV (HSIL+) | 76.0 Percent |
Secondary
Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection.
Time frame: 10 months
Population: Evaluable samples that had also had HPV reflex testing
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SurePath Plus | Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection. | Sensitivity (ASC-US) | 78.8 percent |
| SurePath Plus | Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection. | Specificity (ASC-US) | 45.7 percent |
| SurePath Pap | Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection. | Sensitivity (ASC-US) | 87.9 percent |
| SurePath Pap | Compare the Sensitivity and Specificity of the BD SurePath Plus Pap Test to the SurePath Pap With HPV Reflex Testing for CIN2+ Disease Detection. | Specificity (ASC-US) | 41.5 percent |