FDA Approves New Use for cobas HPV Cervical Cancer Screening Test

The cobas HPV test for cervical cancer screening is now FDA-approved for use on the high-throughput cobas 6800/8800 Systems, according to Roche (Genentech), the developer of the cobas platform.¹

The cobas HPV test identifies the existence of HPV DNA in cervical samples. High-risk, persistent HPV infections can become precancerous lesions and subsequently develop into cervical cancer if not properly treated.

The cobas 6800 and cobas 8800 Systems, which are used for routine molecular resting, deliver “fully integrated, automated solutions that serve the areas of viral load monitoring, donor screening, sexual health and microbiology,” Roche explained in a press release.

The technology provides “Increased throughput, fast turnaround time, and complete track connectivity validated for molecular testing, providing users with greater flexibility to consolidate their in vitro diagnostic and laboratory developed testing to a single system while increasing overall workflow efficiencies,” Roche added.

The cobas HPV test was clinically validated for use on the cobas 6800/8800 System in the registrational IMPACT trial, data from which the FDA evaluated when making its approval decision. The study enrolled approximately 35,000 women in the United States. The specific data from the study have not yet been made publicly available.

“The approval of our HPV test for the cobas 6800 and 8800 Systems enables molecular laboratories to achieve the efficiency and scale they need to meet the demands of high-volume cervical screening programs,” Thomas Schinecker, CEO, Roche Diagnostics, said in the press release. “This is critical as most healthcare providers in the US have adopted HPV testing as part of their cervical cancer screening protocol, with the ultimate goal of preventing cervical cancer in all women.”

The cobas HPV test was previously approved for the cobas 4800 System, based on data from the ATHENA trial (NCT00709891). The cobas 4800 HPV test specifically detects the presence of the DNA of HPV genotypes 16 and 18. These 2 genotypes are the cause of about 70% of all cervical cancers. The test, using only 1 patient sample, also reports on the presence of the 12 other high-risk HPV genotypes.

The FDA also recently approved the CINtec® PLUS Cytology test as the first biomarker-based triage test for women whose primary cervical cancer screening results are positive for the HPV using the cobas® 4800 HPV Test.²

The CINtec PLUS Cytology test allows clinicians to identify HPV-positive women who are more at risk of developing cervical precancers, identifying those patients who need to immediately receive additional diagnostic work.

The CINtec PLUS Cytology simultaneously detects p16 and Ki-67. When a cell expresses both of these biomarkers, there is a high likelihood that the patient has transforming HPV infections that can potentially progress to either precancer or cancer.³

The FDA made its decision based on data from the IMPACT trial. The study evaluated the CINtec PLUS Cytology test as a triage tool in several screening scenarios among a population of more than 35,000 women.

Previous research demonstrated the potential of the CINtec PLUS Cytology test. One study was a retrospective analysis that compared CINtec PLUS Cytology with Pap cytology triage in HPV-positive test results from a subset of 7727 women aged ≥25 years enrolled in the ATHENA trial.⁴ All of these patients had a valid cervical biopsy and cobas HPV Test results, and had been referred to colposcopy. The investigators were able to retrospectively conduct p16/Ki-67 dual-stained cytology using residual cytologic material collected at the time the patients were enrolled on the ATHENA trial.

The study showed increased sensitivity with the CINtec PLUS Cytology test at 74.9% compared with 51.9% with Pap cytology (P <.0001). The specificity rates were comparable at 74.1% versus 75%, respectively (P = .3198).

The PALMS study assessed CINtec PLUS Cytology in 27,349 women aged ≥18 years across 5 countries in Europe who received routine screening for cervical cancer.⁵ All women received HPV testing, pap cytology and p16/Ki-67 immunostaining with CINtec PLUS Cytology. Women with positive test results were referred for colposcopy, with the exception of women aged <30 years who only tested positive for HPV.

The investigators observed similar rates of p16/Ki-67 dual-stained cytology positivity as the incidence of abnormal Pap cytology results. The p16/Ki-67 positivity rates were <50% of the HPV+ testing rates.

Across all women, the sensitivity of CINtec PLUS Cytology was higher than Pap cytology at 86.7% versus 68.5% (P <.001) for detecting high-grade cervical intraepithelial neoplasia, the study’s criterion for referral for colposcopy; the specificity, as with the ATHENA substudy data, were comparable at 95.2% versus 95.4%, respectively (P = .15).

References

1. Roche receives FDA approval for cobas HPV test for use on the cobas 6800/8800 Systems to identify women at risk for cervical cancer. Published April 21, 2020. https://bit.ly/2RTO9pa. Accessed April 21, 2020.
2. Roche receives FDA approval for CINtec PLUS Cytology test to aid clinicians in improving cervical cancer prevention. Published online March 11, 2020. https://bit.ly/2IEgWc5. Accessed March 11, 2020.
3. CINtec® PLUS Cytology. Roche. Last updated March 11, 2020. https://diagnostics.roche.com/global/en/products/tests/cintec-plus.html. Accessed March 11, 2020.
4. Wright TC Jr, Behrens CM, Ranger-Moore J, et al. Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial. Gynecol Oncol. 2017;144(1):51-56. doi: 10.1016/j.ygyno.2016.10.031.
5. Ikenberg H, Bergeron C, Schmidt D, et al. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst. 2013;105(20):1550-1557. doi: 10.1093/jnci/djt235