Evaluation of the Cobas® 4800 HPV Test for the Detection of High-grade Cervical Disease

• ClinicalTrials.gov Identifier: NCT00709891
• Recruitment Status: Completed
• First Posted: July 3, 2008
• Results First Posted: February 9, 2015
• Last Update Posted: February 9, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Diagnostic
• Condition: Human Papilloma Virus (HPV)
• Intervention: Device: cobas® 4800 HPV Test
• Enrollment: 47208

Participant Flow

Recruitment Details
Pre-assignment Details	Participants who had not met the study primary clinical endpoint of ≥ CIN2 were invited to participate in the longitudinal follow-up phase.

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Period Title: Baseline, Cross-sectional Phase
Started	47208
Completed	45758
Not Completed	1450
Period Title: Longitudinal Follow-up Phase
Started	10002 [1]
Completed	5020
Not Completed	4982
[1] Only participants who met study criteria in the Baseline phase started the Follow-up phase.

Baseline Characteristics

Arm/Group Title		Cobas® 4800 HPV Test
Arm/Group Description		The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Overall Number of Baseline Participants		46887
Baseline Analysis Population Description		Eligible population: All participants who met the study inclusion/exclusion criteria, had not been enrolled in the study previously, and had not withdrawn consent before undergoing any study procedures. Of the enrolled population, 321 participants did not meet these criteria.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	46887 participants
		39.8 (12.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	46887 participants
	Female	46887 100.0%
	Male	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Diagnosis of ≥ CIN2
Description	A diagnosis of ≥ CIN2 (cervical intraepithelial neoplasia) included histology results of CIN2, CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.
Time Frame	Baseline to the end of the Baseline period (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

Evaluable ASC-US participant population: All enrolled participants with a diagnosis of atypical squamous cells of undetermined significance (ASC-US).

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description:	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Overall Number of Participants Analyzed	1578
Measure Type: Number; Unit of Measure: Percentage of participants
Positive cobas 4800 HPV test result - n=514	14.0
Negative cobas 4800 HPV test result - n=1064	0.8

2. Secondary Outcome

Title	Percentage of Participants With a Diagnosis of ≥ CIN3
Description	A diagnosis of ≥ CIN3 (cervical intraepithelial neoplasia) included histology results of CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.
Time Frame	Baseline to the end of the study (up to 5 years, 1 month)

Outcome Measure Data

Analysis Population Description

Evaluable ASC-US participant population: All enrolled participants with a diagnosis of atypical squamous cells of undetermined significance (ASC-US).

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description:	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Overall Number of Participants Analyzed	1578
Measure Type: Number; Unit of Measure: Percentage of participants
Positive cobas 4800 HPV test result - n=514	8.4
Negative cobas 4800 HPV test result - n=1064	0.3

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Safety population: All enrolled participants. Non-serious adverse events were not recorded in this study.
Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
All-Cause Mortality
	Cobas® 4800 HPV Test
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Cobas® 4800 HPV Test
	Affected / at Risk (%)
Total	1/47208 (0.00%)
Vascular disorders
Urogenital haemorrhage † 1	1/47208 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Cobas® 4800 HPV Test
	Affected / at Risk (%)
Total	0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Monsonego J, Cox JT, Behrens C, Sandri M, Franco EL, Yap PS, Huh W. Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: data from the ATHENA trial. Gynecol Oncol. 2015 Apr;137(1):47-54. doi: 10.1016/j.ygyno.2015.01.551. Epub 2015 Feb 8.

Wright TC Jr, Stoler MH, Behrens CM, Sharma A, Sharma K, Apple R. Interlaboratory variation in the performance of liquid-based cytology: insights from the ATHENA trial. Int J Cancer. 2014 Apr 15;134(8):1835-43. doi: 10.1002/ijc.28514. Epub 2013 Oct 29.

Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011 Sep;12(9):880-90. doi: 10.1016/S1470-2045(11)70188-7. Epub 2011 Aug 22.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00709891
• Other Study ID Numbers: RD000649; MWP-HPV-159 ( Other Identifier: Roche Molecular Systems, Inc. )
• First Submitted: June 30, 2008
• First Posted: July 3, 2008
• Results First Submitted: January 20, 2015
• Results First Posted: February 9, 2015
• Last Update Posted: February 9, 2015