For in vitro diagnostic use. Others CINtec PLUS Cytology IVD Cervical Carcinoma CINtec® PLUS Cytology RTD001259 US-FDA Mouse Rabbit p16INK4a - E6H4 mouse monoclonal antibody, Ki-67: 274-11AC3V1 rabbit monoclonal antibody 07 478 496 001 7 478 496 001 07478496001 7478496001 07478496001 CINtec PLUS CYTOLOGY PMA CINtec PLUS Cytology 04015630977215 Reagents, kits 760-100 100 test Not Available true The CINtec® PLUS Cytology test is a qualitative immunocytochemical assay intended for the simultaneous detection of the p16INK4a and Ki-67 proteins in cervical specimens collected by a clinician using an endocervical brush/spatula or broom collection device and placed in the ThinPrep® Pap Test PreservCyt® Solution. The CINtec PLUS Cytology test includes a ready-to-use cocktail of primary antibodies which contains a mouse monoclonal antibody directed against human p16INK4a (p16) protein (clone E6H4), and a recombinant rabbit monoclonal antibody directed against human Ki-67 protein (clone 274-11AC3V1) for use on the BenchMark ULTRA instrument with 3,3ʹ-diaminobenzidine tetrahydrochloride (DAB) and Fast Red detection systems. The CINtec PLUS Cytology test is indicated: To be used in women 25 – 65 years old with 12 Other High Risk (HR) HPV positive test results using cobas® HPV for use on the cobas® 6800/8800 Systems (cobas® HPV) or the cobas® 4800 HPV Test in primary HPV screening, to determine the need for referral to colposcopy. To be used in women 25 – 65 years old with HPV16/18 positive test results using cobas® HPV or the cobas® 4800 HPV Test in primary HPV screening where the CINtec PLUS Cytology test results will be used in conjunction with the physician’s assessment of patient screening history, other risk factors, and professional guidelines to guide patient management. To be used in women 30 – 65 years old with NILM (Negative for Intraepithelial Lesion or Malignancy) and 12 Other HR HPV positive test results using cobas® HPV or the cobas® 4800 HPV Test in adjunctive cervical cytology and HR HPV screening, to determine the need for referral to colposcopy. To be used in women 30 – 65 years old with NILM (Negative for Intraepithelial Lesion or Malignancy) and HPV16/18 positive test results using cobas® HPV or the cobas® 4800 HPV Test in adjunctive cervical cytology and HR HPV screening where the CINtec PLUS Cytology test results will be used in conjunction with the physician’s assessment of patient screening history, other risk factors, and professional guidelines to guide patient management. Results from the CINtec PLUS Cytology test should be interpreted by a qualified pathologist. en The CINtec PLUS Cytology test contains a set of reagents for the simultaneous immunocytochemical detection of the p16INK4a and Ki-67 proteins in cytological specimens obtained from the uterine cervix. The proteins are detected using a ready-to-use cocktail of primary monoclonal antibodies which contains a monoclonal mouse antibody directed against human p16INK4a protein (clone E6H4) and a primary recombinant rabbit antibody directed against human Ki-67 protein (clone 274-11AC3V1). Following cell conditioning, inhibition of endogenous peroxidase activity and incubation with the primary antibody cocktail, the assay uses two ready-to-use detection systems optimized for use on cervical cytology specimens collected in PreservCyt Solution: a goat anti-mouse secondary antibody covalently attached to HQ haptens (proprietary hapten) and an anti-HQ hapten, horseradish peroxidase (HRP)-conjugated tertiary antibody optimized for the detection of the monoclonal mouse antibody clone E6H4, as shown in Figure 2. a goat anti-rabbit secondary antibody covalently attached to NP haptens (proprietary hapten) and an anti-NP hapten, alkaline-phosphatase (AP)-conjugated tertiary antibody optimized for the detection of the rabbit recombinant antibody clone 274-11AC3V1, as shown in Figure 3. The chromogenic reactions are based on the HRP-mediated conversion of 3,3′-diaminobenzidine tetrahydrochloride (DAB) and the AP-mediated conversion of Fast Red with Naphthol Phosphate resulting in a brown precipitate at the p16INK4a antigen site and a red precipitate at the Ki-67 antigen site, respectively. After automated counterstaining and bluing, a two-step mounting procedure is followed. First, the slide is mounted using an aqueous mounting medium. Subsequently, the slide is coverslipped using a permanent mounting medium. The staining results are evaluated by light microscopy. Figure 2. Detection of human p16INK4a protein. Figure 3. Detection of human Ki-67 protein en

CINtec^® PLUS Cytology

US-FDA

IVD

A woman looking relieved after receiving her CINtec plus cytology test results.

CINtec PLUS Cytology, a biomarker-based triage test to identify transforming HPV infection

Not every HPV-positive woman will develop cervical cancer, so triage can determine who is most at risk and will benefit from more immediate follow-up, and who is at low risk and can be given more time to clear the infection on her own. CINtec PLUS is a triage cytology test that helps stratify disease risk immediately, giving clinicians confidence when selecting the appropriate management for women at every level of risk.

Detect changes at the cellular level:

The CINtec PLUS Cytology test is the only FDA approved triage test that uses dual biomarker technology to simultaneously detect p16 and Ki-67 in women with HPV-positive results.

The co-expression of these two biomarkers within the same cell is a strong indicator that an HPV infection is undergoing oncogenic transformation.

CINtec PLUS Cytology test is approved as a triage test with the cobas HPV test

In HPV primary screening of women ages 25-65

* For HPV16/18+ use as additional information in conjunction with the physician’s assessment of patient screening history, other risk factors, and professional guidelines to guide patient management.

Source: Adapted from CINtec PLUS Cytology package insert; Refer to the CINtec PLUS Cytology package insert for the FDA approved intended use.

For discrepant co-testing results of women ages 30-65 when a woman is HPV positive but has a normal Pap

Source: Adapted from CINtec PLUS Cytology package insert; Refer to the CINtec PLUS Cytology package insert for the FDA approved intended use.

CINtec PLUS Cytology is approved for use on cobas^® 4800/6800/8800 instruments.

The IMPACT Trial:
The landmark registational cervical cancer portfolio trial

Included cobas^® HPV test, CINtec PLUS Cytology test, and CINtec^® Histology
Multicenter, prospective trial enrolling ~35,000 women at 32 collection sites across the US
Representative of routine cervical cancer screening population in the US:
- Ages 25-65
- Non-vaccinated and vaccinated
- Diverse races and ethnicities
More than 5,000 HPV-positive subjects
More than 530 ≥CIN2 disease cases

Risk of disease in Pap normal/HPV+ women (≥CIN2, age 30-65)

CINtec PLUS Cytology provides further risk stratification in 12 other HPV+ women

The addition of the CINtec PLUS Cytology test can provide a more accurate quantification of a woman's risk for high grade disease.

Increased testing sensitivity

When added as a triage to discrepant co-testing results, CINtec PLUS Cytology identified 7 our of 10 women as having cells undergoing oncogenic transformation allowing identification of disease earlier in their screening process.

Percentage of disease detected with CINtec PLUS in Pap normal/HPV+ women (≥CIN2, age 30-65)

CINtec PLUS Cytology offers greater sensitivity compared to Pap cytology

CINtec PLUS Cytology improves disease detection independent of genotype, patient age, or vaccination status.

Percentage of disease detected with CINtec PLUS (≥CIN2, age 25-65)

Integrates with automated testing procedures to improve efficiency

CINtec PLUS Cytology is performed from the same ThinPrep sample as HPV and Pap tests, and run on the BenchMark ULTRA. The BenchMark ULTRA system is a fully automated immunohistochemistry and in situ hybridization slide staining system, offering multiple features designed to provide diagnostic confidence to histopathology laboratories worldwide. With 30 independent slide drawers, the system gives histotechnologists continuous random access and supports single-piece workflow, which numerous studies have shown improves laboratory operational efficiency.

Learn more

Key resources to learn more

The following publications provide further evidence of the clinical utility of p16/Ki-67 dual staining in cervical cancer screening:

CINtec PLUS Cytology package insert.
T.C. Wright Jr. et al., Triaging HPV-Positive Women with p16/Ki-67 Dual-stained Cytology: Results from a Sub-study Nested into the ATHENA Trial. Gynecologic Oncology 144 (2017) 51–56.Gynecol Oncol. 2017 Jan;144(1):51-56. doi: 10.1016/j.ygyno.2016.10.031.
Wentzensen N., et al., Performance of p16/Ki-67 Immunostaining to Detect Cervical Cancer Precursors in a Colposcopy Referral Population. Clin Cancer Res. 2012 Aug 1;18(15):4154-62. doi: 10.1158/1078-0432.CCR-12-0270. Epub 2012 Jun 6.

Considering implementing CINtec PLUS Cytology in your lab?

Roche experts will be with you every step of the way

Complete this form if you would like more information about implementing CINtec PLUS Cytology in your lab

Here is a checklist of what you need to implement CINtec PLUS Cytology in your lab:

☐ VENTANA BenchMark ULTRA instrument with required software

☐ Required bulks and ancillaries

BenchMark ULTRA
Ordering code	Material description
5424534001	ULTRA LCS
5353955001	Reaction Buffer Concentrate (10X)
5424569001	ULTRA CCI
5266726001	Hematoxylin
5266769001	Bluing reagent

☐ Additional supplies

Supplies required but not provided
Part of Catalogue #	Vendor	Material description
70126-002	Hologic	ThinPrep^® Arcless Microscope Slides or ThinPrep^® Microscope Slides for Special Processing—75 slides/box
1001350487	Sigma	CC Mount^™ aqueous mounting media

☐ 25-30 residual HSIL or known positive ThinPrep® sample vials

☐ Schedule lab implementation & training with a Roche expert

Lab Implementation & Training sessions are offered to all customers to ensure a smooth, successful implementation of CINtec PLUS Cytology into the laboratory. Sessions can last approximately 2-5 days depending on the size of the lab and number of staff requiring training.

Training includes:

Slide preparation & staining with laboratory staff
Interpretation training sessions, including interactive glass slide review, with Cytotechnologists and Pathologists
Interpretation proficiency testing

Reagent catalog

IHC and ISH reagents and ancillaries

To view associated reagents, ancillaries and bulks, please visit the Roche Tissue Diagnostics reagent catalog.

Reagent catalog

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CINtec^® PLUS Cytology

Detect changes at the cellular level: