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

Empowering greater certainty in identifying cervical disease with dual-stain cytology

Not every HPV-positive woman will develop cervical cancer, but CINtec PLUS Cytology can better stratify her risk and identify cervical disease earlier in her cervical screening journey

CINtec PLUS Cytology is a dual-stain biomarker test that empowers clinicians to determine if their patients need immediate intervention or routine follow-up testing. The dual-stain biomarker technology provides a more objective evaluation (when compared to Pap cytology) to go beyond risk-based assessment alone and actually identify evidence of cervical disease in patients during their screening visit.

More than half of patients with abnormal cervical screening results will NOT return for follow-up testing, meaning cervical disease may be missed

The CINtec PLUS dual-stain cytology test can be performed on the same cervical sample that is collected for HPV testing and/or Pap cytology during a patient's cervical screening visit. From that same cervical sample, CINtec PLUS Cytology results stratify risk further than the initial co-testing or primary HPV screening results and provide objective evidence of HPV infection transitioning into cervical disease. In addition, a negative dual-stain cytology result provides greater reassurance than a negative Pap cytology result that there is truly no disease. Therefore, when it comes time to follow-up in one year, clinicians can be more confident that disease was not missed, especially knowing that over half of patients do not return for their follow-up testing.

Now included in
ASCCP* guidelines

The recommendations for use of dual-stain cytology with CINtec PLUS were added in April 2024.

*American Society for Colposcopy and Cervical Pathology

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Detect changes at the cellular level:

CINtec PLUS dual-stain cytology, based on immunocytochemistry staining, provides objective and enhanced visual clarity to detect co-expressing biomarkers of HPV-related oncogene activity strongly associated with precancerous cellular changes. This is in comparison to Pap cytology, where disease identification is based on morphological characteristics, which can be difficult to assess objectively.

CINtec <i>PLUS</i> dual-stain cytology is approved for use as:

CINtec PLUS dual-stain cytology is approved for use as:

Triage testing following HPV primary screening for HPV positive results in 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.

Reflex testing following discrepant co-testing results in women ages 30-65

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 IMproved Primary screening And Colposcopy Triage (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

CINtec PLUS Cytology provides greater risk stratification than Pap cytology

CINtec PLUS Cytology detects the co-expression of the biomarkers p16 and Ki-67 within a single cell to both identify evidence of HPV infections transitioning into cervical disease and further stratify risk beyond HPV genotpying alone. This means that a negative CINtec PLUS Cytology result substantially lowers the risk of remaining undetected disease in HPV-positive patients.

CINtec PLUS Cytology detects more disease than Pap cytology

Cervical disease detected in HPV positive patients when triage testing was done with CINtec PLUS Cytology versus Pap cytology

CINtec PLUS Cytology is an objective biomarker test used to triage abnormal cervical cancer screening results. By better informing clinicians, the most appropriate patient care can be determined: immediate intervention with colposcopy or routine follow-up testing.

The key to ELIMINATING cervical cancer is more than a product. It's a path. CINtec PLUS Cytology is one component of the Roche Cervical Cancer Portfolio—the only single portfolio covering every critical step in the cervical cancer pathway:

Key resources to learn more

CINtec PLUS Cytology - Method Sheet. 1018621US Rev D. 2024-06-13.
Tiro et al. Delivering Guideline-Concordant Care for Patients With High-Risk HPV and Normal Cytologic Findings. JAMA. 01/2025.
ASCCP Management Guidelines and the Enduring Guidelines Process https://www.asccp.org/clinical-practice/guidelines/enduring-guidelines Accessed 02/2025.
Kuroki et al. Addressing unmet basic needs to improve colposcopy adherence among women with abnormal cervical cancer screening. J Low Genit Tract Dis. 04/2022.
Wright TC Jr, et al. Clinical validation of p16/Ki-67 dual-stained cytology triage of HPV-positive women: Results from the IMPACT trial. Int J Cancer. 2022 Feb 1;150(3):461-471.
Wentzensen N, et al. Clinical Evaluation of Human Papillomavirus Screening With p16/Ki-67 Dual Stain Triage in a Large Organized Cervical Cancer Screening Program. JAMA Intern Med. 2019 Jul 1;179(7):881-888.
Clarke MA, et al. Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women. JAMA Oncol. 2019 Feb 1;5(2):181-186.

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

☐ VENTANA BenchMark ULTRA or ULTRA PLUS instrument with required software

☐ Required bulks and ancillaries

BenchMark ULTRA and ULTRA PLUS
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. Roche also offers a Lab to Clinician Education Program (LCEP) to notify and train clinicians on why and how to order CINtec PLUS Cytology from your lab.

Training includes:

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

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CINtec^® PLUS Cytology

Not every HPV-positive woman will develop cervical cancer, but CINtec PLUS Cytology can better stratify her risk and identify cervical disease earlier in her cervical screening journey