Human Papillomavirus Infection
Conditions
Keywords
Cervix Cancer, Cervical Intraepithelial Neoplasia (CIN), Human Papillomavirus Virus (HPV), APTIMA HPV Assay, FDA-Approved HPV DNA Test, TIGRIS DTS (direct tube sampling) System, Clinical Sensitivity (%), Clinical Specificity (%), Positive Predictive Value [PPV] (%), Negative Predictive Value [NPV] (%), Atypical Squamous Cells Undetermined Significance (ASC-US), Relative Risk
Brief summary
The purpose of this study is to provide data on the performance of the APTIMA HPV Assay using the TIGRIS System in detecting HPV types that may cause cervical cancer.
Detailed description
The primary objective of the clinical trial is to evaluate the APTIMA HPV Assay, using the TIGRIS System, in cervical cancer screening programs. This will be achieved by determining the performance of the assay for detecting high-risk human papillomavirus (HPV) types in women with known cervical disease status. The assay will be evaluated in sample populations of women with ASC-US Pap test results (ASC-US results) and women 30 years of age or older (30+ years of age) with negative (NILM) cytology results.
Interventions
DEVICEAPTIMA HPV Assay
The APTIMA HPV Assay is an in vitro nucleic acid amplification test (NAAT) that qualitatively detects human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) from 14 HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) that are associated with cervical cancer (high-risk types). The assay cannot determine the specific high-risk HPV type(s) present and does not cross-react with 5 HPV types that are considered non-oncogenic (not associated with cervical cancer; types 6, 11, 42, 43, and 44).
DEVICEFDA-Approved HPV DNA Test
A FDA-Approved HPV DNA Test is used as the comparator assay.
Sponsors
Gen-Probe, Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Female 21 years or older (ASC-US study only) * Female 30 years or older (Adjunct and ASC-US studies) * Subject attending a participating clinic and undergoing a Pap screening exam during the clinic visit * Ability to comprehend and sign an IRB-approved Informed Consent Form
Exclusion criteria
* Diagnosis of cervical disease (cancer or precancerous condition) in the past 12 months * Abnormal Pap test result in the past 12 months * Subject under 18 years of age and consenting to the study without the presence of their parent or legal guardian * Known to be pregnant * Having an illness or medical condition that could interfere with or affect the conduct, results, and/or completion of the clinical trial * Having an illness or medical condition that the investigator or physician feels would create an unacceptable risk to the subject if she enrolled into the clinical trial * Prior vaccination for HPV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Baseline Evaluation | Adjunct 30+ yrs. Population: Aptima HPV Assay Performance for Detecting CIN2+: Compare Clinical Performance of the Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ |
| Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Baseline Evaluation | Adjunct Study Arm: 30+ yrs. Population: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+: Compare Clinical Performance of the Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Baseline Evaluation | ASC-US Study Arm: 21+ yrs. Population: Aptima HPV assay performance on Tigris System for detecting CIN2+ (All Biopsies) |
| ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies) | Baseline Evaluation | ASC\_US Study Arm: 21+ yrs. Population for Detecting CIN2+ (All Biopsies): FDA-Approved HPV DNA Assay |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adjunct (i.e. Normal Pap) The Adjunct study will evaluate APTIMA HPV Assay performance for detecting high-risk HPV types in female subjects 30+ years of age with negative (NILM) cytology results from routine Pap testing. This will be accomplished by evaluating the assay performance compared to known cervical disease status at baseline and after a 3-year follow-up period.
APTIMA HPV Assay: The APTIMA HPV Assay is an in vitro nucleic acid amplification test (NAAT) that qualitatively detects human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) from 14 HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) that are associated with cervical cancer (high-risk types). The assay cannot determine the specific high-risk HPV type(s) present and does not cross-react with 5 HPV types that are considered non-oncogenic (not associated with cervical cancer; types 6, 11, 42, 43, and 44). | 10,871 |
| ASC-US The ASC-US study will determine the sensitivity and specificity of the APTIMA HPV Assay for detecting high-risk HPV types in subjects with ASC-US Pap test results from routine Pap testing and known cervical disease status (based on colposcopic biopsy results).
APTIMA HPV Assay: The APTIMA HPV Assay is an in vitro nucleic acid amplification test (NAAT) that qualitatively detects human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) from 14 HPV types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) that are associated with cervical cancer (high-risk types). The assay cannot determine the specific high-risk HPV type(s) present and does not cross-react with 5 HPV types that are considered non-oncogenic (not associated with cervical cancer; types 6, 11, 42, 43, and 44). | 958 |
| Total | 11,829 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 3-Year Follow-up | Lost to Follow-up | 17 | 0 |
| Baseline Evaluation | Inevaluable | 686 | 223 |
| Baseline Evaluation | No colposcopy visit | 62 | 0 |
| Baseline Evaluation | W/D, later determined to be ineligible | 25 | 0 |
Baseline characteristics
| Characteristic | Adjunct (i.e. Normal Pap) | ASC-US | Total |
|---|---|---|---|
| Age, Continuous | 44.1 Years STANDARD_DEVIATION 10.1 | 33.8 Years STANDARD_DEVIATION 10.3 | 43.3 Years STANDARD_DEVIATION 10.5 |
| Age, Customized 21 - <30 years | 0 participants | 418 participants | 418 participants |
| Age, Customized 30 - <40 years | 4199 participants | 266 participants | 4465 participants |
| Age, Customized 40+ years | 6672 participants | 274 participants | 6946 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3421 Participants | 195 Participants | 3616 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6881 Participants | 712 Participants | 7593 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 569 Participants | 51 Participants | 620 Participants |
| Gender Female | 10871 Participants | 958 Participants | 11829 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 76 Participants | 12 Participants | 88 Participants |
| Race (NIH/OMB) Asian | 622 Participants | 27 Participants | 649 Participants |
| Race (NIH/OMB) Black or African American | 1358 Participants | 218 Participants | 1576 Participants |
| Race (NIH/OMB) More than one race | 128 Participants | 28 Participants | 156 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 48 Participants | 1 Participants | 49 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1808 Participants | 106 Participants | 1914 Participants |
| Race (NIH/OMB) White | 6831 Participants | 566 Participants | 7397 Participants |
| Region of Enrollment United States | 10871 participants | 958 participants | 11829 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11,644 | 0 / 1,252 |
| serious Total, serious adverse events | 0 / 11,644 | 0 / 1,252 |
Outcome results
Primary
Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+
Adjunct 30+ yrs. Population: Aptima HPV Assay Performance for Detecting CIN2+: Compare Clinical Performance of the Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+
Time frame: Baseline Evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Positive, CIN2+ | 15 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Negative, CIN2+ | 5 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Positive, No Disease | 299 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Negative, No Disease | 500 participants |
95% CI: [53.1, 88.8]
95% CI: [59.2, 65.9]
95% CI: [3.4, 5.8]
95% CI: [98.1, 99.6]
95% CI: [1.8, 13.1]
Primary
Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+
Adjunct Study Arm: 30+ yrs. Population: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+: Compare Clinical Performance of the Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+
Time frame: Baseline Evaluation
Population: 18 women with Aptima HPV results did not have FDA-Approved DNA test results due to insufficient volume of the cytology specimen for a N of 801 compared to a N of 819 for the Aptima HPV assay results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Positive, CIN2+ | 16 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Negative, CIN2+ | 3 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Positive, No Disease | 401 participants |
| APTIMA HPV Assay | Adjunct Study Arm: Compare Assay Performance for FDA-Approved HPV DNA Assay to a FDA-Approved HPV Assay for Detecting CIN2+ | Assay Negative, No Disease | 381 participants |
95% CI: [62.4, 94.5]
95% CI: [45.2, 52.2]
95% CI: [2.9, 4.4]
95% CI: [98.1, 99.8]
95% CI: [1.4, 16.7]
Secondary
ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies)
ASC-US Study Arm: 21+ yrs. Population: Aptima HPV assay performance on Tigris System for detecting CIN2+ (All Biopsies)
Time frame: Baseline Evaluation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| APTIMA HPV Assay | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, CIN2+ | 79 participants |
| APTIMA HPV Assay | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, CIN2+ | 12 participants |
| APTIMA HPV Assay | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, No Disease | 315 participants |
| APTIMA HPV Assay | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, No Disease | 533 participants |
| FDA-Approved HPV DNA Test | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, No Disease | 433 participants |
| FDA-Approved HPV DNA Test | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, CIN2+ | 79 participants |
| FDA-Approved HPV DNA Test | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, No Disease | 343 participants |
| FDA-Approved HPV DNA Test | ASC-US Study Arm: Aptima HPV Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, CIN2+ | 10 participants |
95% CI: [78.4, 92.3]
95% CI: [59.6, 66]
95% CI: [18.1, 22]
95% CI: [96.5, 98.8]
Secondary
ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies)
ASC\_US Study Arm: 21+ yrs. Population for Detecting CIN2+ (All Biopsies): FDA-Approved HPV DNA Assay
Time frame: Baseline Evaluation
Population: 74 women with Aptima HPV assay results did not have FDA-Approved HPV DNA test results primarily due to insufficient volume of the cytology specimen for an N of 865 results for the FDA-Approved HPV DNA assay compared to 939 results for the Aptima HPV assay.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| APTIMA HPV Assay | ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, CIN2+ | 79 participants |
| APTIMA HPV Assay | ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, CIN2+ | 10 participants |
| APTIMA HPV Assay | ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Positive, No Disease | 343 participants |
| APTIMA HPV Assay | ASC-US Study Arm: FDA-Approved HPV DNA Assay Performance for Detecting CIN2+ (All Biopsies) | Assay Negative, No Disease | 433 participants |
95% CI: [80.5, 93.8]
95% CI: [52.3, 59.3]
95% CI: [17, 20.4]
95% CI: [96.2, 98.8]