FDA Approves Expanded Use of CINtec PLUS Cytology Test to Prevent Cervical Cancer in HPV+ Women


The FDA has approved the expanded use of the CINtec PLUS Cytology assay for women who undergo cervical cancer screening and test positive for high-risk types of human papillomavirus.

The FDA has approved the expanded use of the CINtec PLUS Cytology assay for women who undergo cervical cancer screening and test positive for high-risk types of human papillomavirus (HPV), according to an announcement from Roche.1

The test is capable of identifying the presence of p16 and Ki-67 simultaneously. If a single cell expresses both of these biomarkers, there is a higher likelihood that the patient will have transforming HPV infection capable of progressing to either pre-cancer or cancer.

The regulatory decision was based on findings from the registrational IMPACT trial, for which publication of the full data is pending, according to Roche. In the trial, investigators examined the CINtec PLUS Cytology test as a triage tool in several screening scenarios among a population of over 35,000 women. The approval for expanded use provides laboratories with access to the complete Roche Cervical Cancer Portfolio in the United States; this is comprised of the cobas HPV test, CINtec PLUS Cytology, and CINtec Histology.

“With our portfolio of cervical cancer tests and automated testing platforms, we are committed to providing clinicians and laboratories with the best tools possible to protect women’s health,” Thomas Schinecker, CEO of Roche Diagnostics, stated in a press release.

“This expanded indication for CINtec PLUS Cytology gives laboratories the flexibility to triage cobas HPV test results on their choice of cobas Systems and deliver accuracy needed to reliably detect HPV infections that are starting to cause cellular changes that could lead to cancer,” Schinecker added. “The biomarker information helps to clarify a women’s risk of disease, reduce the potential for over- or under-treatment, and is a major step forward in individualizing a woman’s care.”

The potential of the CINtec PLUS Cytology test has also been demonstrated in a retrospective analysis which compared the CINtec PLUS Cytology with Pap cytology triage in HPV-positive test results collected from a subset of 7727 women aged 25 years of age or older who were enrolled in the ATHENA trial.2 All participants had a valid cervical biopsy and cobas HPV Test results, and all had been referred to colposcopy. The investigators retrospectively conducted p16/Ki-67 dual-stained cytology by utilizing residual cytologic material that had been collected at the time of enrollment on the trial.

Results showed increased sensitivity with the CINtec PLUS Cytology test, at 74.9% versus 51.9% with Pap cytology (P <.0001). The specificity rates between the 2 approaches proved to be similar, at 74.1% versus 75%, respectively (P = .3198).

In the PALMS study, investigators evaluated CINtec PLUS Cytology in a total of 27,349 women aged 18 years or older across 5 countries in Europe who underwent routine screening for cervical cancer.3 All of those included in the analysis received HPV testing, pap cytology, and p16/Ki-67 immunostaining with CINtec PLUS Cytology. Women who tested positive were referred for colposcopy, with the exception of women who were younger than 30 years and who only tested positive for HPV.

Comparable rates of p16/Ki-67 dual-stained cytology positivity as the incidence of abnormal Pap cytology results were reported. Moreover, the p16/Ki-67 positivity rates were less than 50% of the HPV-positive testing rates.

Across all women, the sensitivity of CINtec PLUS Cytology was found to be higher than that of Pap cytology, at 86.7% versus 68.5% (P <.001), respectively, for detecting high-grade cervical intraepithelial neoplasia, which was the study’s criterion for referral for colposcopy. As had been observed with the ATHENA substudy data, specificity rates proved to be comparable between the arms, at 95.2% versus 95.4%, respectively (P = .15).

Before the FDA approvals for the use of CINtec PLUS Cytology for the triage of women with HPV positivity using the cobas HPV test on the cobas 4800 or cobas 6800/8800 Systems, this assay was also utilized as a triage test for HPV-positive results and mildly abnormal Pap cytology results in Europe, Asia, South America, Canada, and Australia.


  1. Roche receives FDA approval for expanded use of the CINtec PLUS Cytology test to aid clinicians in preventing cervical cancer. News release. Roche. September 16, 2020. Accessed September 16, 2020. https://bit.ly/3hxW0m8.
  2. 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
  3. 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
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