Clinical Evaluation of the APTIMA® HPV Assay and Comparison With the HR HC2® Test Using LBC ThinPrep® Specimens

Study Overview
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Brief Summary
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To assess and compare the performance of the HR HPV HC2® test (Qiagen/Digene) and the APTIMA® HPV Assay (Hologic) using LBC Specimens (ThinPrep® Pap Test) for the detection of HPV infection and high-grade CIN lesions in a screening population of women 30 years of age or older in Germany.

Detailed Description
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The study is conducted in the areas of Tuebingen, Freiburg and Saarbruecken in Germany. In total, 10.000 ThinPrep® LBC cervical samples were collected from June 2009 to May 2012. Liquid based cytology (LBC) was performed by a central laboratory in Saarbruecken. Human papilloma virus (HPV) testing with the HR HPV HC2® test and APTIMA® HPV Assay were performed at the Section of Experimental Virology, Institute of Medical Virology, University Clinic of Tuebingen, Germany (UKT). Within a follow-up phase women who tested positive in any test at baseline will be monitored over a period of 10 years. Study close out visit: In addition, approximately 5 years after baseline ThinPrep® LBC cervical samples will be collected from a random sample of 4000 study participants who tested triple negative at baseline for determination of the longitudinal negative predictive value (NPV) and HPV related disease after a 5 year period. Women who tested positive in any test will undergo colposcopy.

Official Title
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Clinical Evaluation of the APTIMA® HPV Assay and Comparison With the HR HPV HC2® Test in Women 30 Years of Age or Older Using LBC ThinPrep® Pap Test Specimens

Conditions
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Human Papilloma Virus Infection

Intervention / Treatment
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* Other: Thinprep® LBC
* Other: APTIMA® HPV Assay
* Other: HR HC2® HPV DNA
* Other: Colposcopy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Women aged 30 - 60 years Women attending gynaecological practices for routine screening Women who gave informed consent to participation in the study Exclusion criteria: Women with hysterectomy or known destructive therapy to the cervix Women who are pregnant Women with an abnormal cytology result during the previous 6 months Women with known HIV infection or history of transplants Women vaccinated against HPV Women participating in another research protocol

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Triple negative women<br>Women 30 years of age or older coming for routine cervical screening who tested triple negative at baseline with the interventions: Thinprep® LBC, HR HC2® HPV DNA and APTIMA® HPV Assay | Other: Thinprep® LBC<br>* liquid based cytology<br>Other: APTIMA® HPV Assay<br>* in vitro diagnostic test<br>Other: HR HC2® HPV DNA<br>* in vitro diagnostic test<br>Other: Colposcopy<br>* Colposcopy<br>|
| Women tested positive<br>Women who tested positive in any of the tests Thinprep® LBC, HR HC2® HPV DNA or APTIMA® HPV Assay will undergo colposcopy and be followed up over a ten year period and subjects who tested positive during the follow up assessment will be followed up over a 5 year period on a yearly basis | Other: Thinprep® LBC<br>* liquid based cytology<br>Other: APTIMA® HPV Assay<br>* in vitro diagnostic test<br>Other: HR HC2® HPV DNA<br>* in vitro diagnostic test<br>Other: Colposcopy<br>* Colposcopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall high risk (HR) HPV prevalence with HR HC2® HPV and APTIMA® test |  | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of LBC, HC2® and APTIMA® tests |  | Baseline, 5 years | 
| Specificity of LBC, HC2® and APTIMA® tests |  | Baseline, 5 years | 
| Positive Predictive Value (PPV) of LBC, HC2® and APTIMA® tests |  | Baseline | 
| Negative Predictive Value (NPV) of LBC, HC2® and APTIMA® tests |  | Baseline | 
| Prevalence of HR HPV infection by age with HC2® and APTIMA |  | Baseline, 5 years | 
| Cross sectional association between HR HPV infection (HC2® and APTIMA) and LBC diagnosis | Linear regression models will be used for determination of cross sectional associations between HR HPV Infection and LBC diagnosis. | Baseline, 5 years | 
| Relative risk of cervical disease for positive tested women | Analysis of study results at baseline and follow-up visits. Calculation of relative risks of cervical disease for women who are positive for LBC, HC2® and/or APTIMA® test compared to those being negative for any of the three tests at the baseline visit. | Baseline, 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years | 
| Cumulative risk of cervical diseases for positive tested women at 5 years |  | Baseline, 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical cancer screening, High risk Human Papillomavirus, Aptima HPV Assay