Predicate Devices

Not Applicable (De Novo request)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes an immunohistochemistry (IHC) test and its associated detection kit and automated staining instrument. There is no mention of any software, algorithms, image processing, or data analysis that would suggest the use of AI or ML. The test is interpreted by a pathologist using light microscopy.

Therapeutic

No

Explanation: This device is an in-vitro diagnostic (IVD) test intended to aid in the diagnosis of cervical intraepithelial neoplasia (CIN) by improving the consistency of diagnosis through immunohistochemistry. It does not directly treat or prevent a disease; rather, it provides diagnostic information that informs treatment decisions.

Diagnostic

Yes

The device is intended as an adjunct to examination of H&E stained slides to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN), which is a diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device is described as an immunohistochemistry (IHC) test comprised of an antibody and detection kit, which are physical reagents used in a laboratory setting. It is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's a "qualitative immunohistochemistry (IHC) test" for assessing a protein (p16thK4a) in "formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues." This involves testing a sample taken from the human body in vitro (outside the body).
Purpose: The test is intended as an "adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN)." This is a diagnostic purpose, aiding in the identification and classification of a disease state.
Device Description: It describes a "single dispenser IHC assay system" and a "detection kit," which are components used in laboratory testing of biological samples.
Anatomical Site: It specifies "Cervical punch biopsy tissues," which are human biological specimens.
Intended User / Care Setting: It indicates "Pathologist / Clinical laboratory setting," which are typical users and settings for IVD tests.

The core function of the device is to perform a test on a biological sample (cervical tissue) outside the body to provide information that assists in a medical diagnosis (CIN). This aligns directly with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

CINtec Histology is a qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4. and is intended for use in the light microscopic assessment of the p16thK4a protein in formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues using OptiView DAB IHC Detection Kit on a VENTANA BenchMark ULTRA instrument. The test is indicated as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN). Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information.

Product codes (comma separated list FDA assigned to the subject device)

PRB

Device Description

The CINtec Histology test is a single dispenser IHC assay system comprised of an anti-p16 primary antibody optimized for use with the BenchMark ULTRA automated slide staining instrument and the OptiView DAB IHC Detection Kit. The antibody is diluted in a Tris-HCl buffer containing carrier protein and 0.1% ProClin 300 as a preservative, and provided as a ready-to-use liquid in a FloLock dispenser. CINtec Histology is available in a 50 test size and a 250 test size.

The OptiView DAB IHC Detection Kit (OptiView) is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit primary antibodies and is comprised of 6 dispensers packaged together in one box. The components of the OptiView DAB IHC Detection Kit are as follows:

Component	Content
OptiView Peroxidase Inhibitor	3.0% hydrogen peroxide solution.
OptiView HQ Universal Linker	Cocktail of HQ-labeled antibodies (goat anti-mouse IgG, goat anti-mouse IgM and goat anti-rabbit) (

Regulation Number and Section

§ 864.1865 Cervical intraepithelial neoplasia (CIN) test system.

(a)
Identification. A cervical intraepithelial neoplasia (CIN) test system is a device used to detect a biomarker associated with CIN in human tissues. The device is indicated as an adjunct test and not to be used as a stand-alone device. The test results must be interpreted in the context of the patient's clinical history including, but not limited to, prior and current cervical biopsy results, Papanicolaou (Pap) test results, human papillomavirus (HPV) test results, and morphology on hematoxylin and eosin (H&E) stained sections. This device is not intended to detect the presence of HPV.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information:
(i) The indications for use must specify the biomarker that is intended to be identified and its adjunct use (
e.g., adjunct to examination of H&E stained slides) to improve consistency in the diagnosis of CIN.(ii) Summary of professional society recommendations, as applicable.
(iii) A detailed device description including:
(A) A detailed description of all test components, including all provided reagents and required, but not provided, ancillary reagents.
(B) A detailed description of instrumentation and equipment, including illustrations or photographs of non-standard equipment or manuals.
(C) If applicable, detailed documentation of the device software, including, but not limited to, stand-alone software applications and hardware-based devices that incorporate software.
(D) A detailed description of appropriate positive and negative controls that are recommended or provided.
(E) Detailed specifications for sample collection, processing, and storage.
(F) A detailed description of methodology and assay procedure.
(G) A description of the assay cutoff (the medical decision point between positive and negative) or other relevant criteria that distinguishes positive and negative results, including the rationale for the chosen cutoff or other relevant criteria and results supporting validation of the cutoff.
(H) Detailed specification of the criteria for test results interpretation and reporting.
(iv) Detailed information demonstrating the performance characteristics of the device, including:
(A) Analytical specificity studies such as, but not limited to, antibody characterization (
e.g., Western Blot, peptide inhibition analysis), studies conducted on panels of normal tissues and neoplastic tissues, interference by endogenous and exogenous substances as well as cross-reactivity, as applicable.(B) Device analytical sensitivity data generated by testing an adequate number of samples from individuals with the target condition including limit of blank, limit of detection, and limit of quantification, as applicable.
(C) Device precision/reproducibility data to evaluate within-run, between-run, between-day, between-lot, between-site, between-reader, within-reader and total precision, as applicable, using a panel of samples covering the device measuring range and/or the relevant disease categories (
e.g. No CIN, CIN1, CIN2, CIN3, cervical cancer) and testing in replicates across multiple, nonconsecutive days.(D) Device robustness/guardbanding studies to assess the tolerance ranges for various critical test and specimen parameters.
(E) Device stability data, including real-time stability and shipping stability under various storage times, temperatures, and freeze-thaw conditions.
(F) Data from a clinical study demonstrating clinical validity using well-characterized prospectively or retrospectively obtained clinical specimens, as appropriate, representative of the intended use population. The study must evaluate the consistency of the diagnosis of CIN, for example, by comparing the levels of agreements of diagnoses rendered by community pathologists to those rendered by a panel of expert pathologists. Agreement for each CIN diagnostic category (
e.g., No CIN, CIN1, CIN2, CIN3, cancer) and for alternate diagnostic categories (e.g., No CIN, low grade squamous intraepithelial lesion (LSIL)-histology, high grade squamous intraepithelial lesion (HSIL)-histology, cancer) between reference diagnosis by expert pathologist and community pathologist must be evaluated, as applicable. In addition, agreements for CIN binary categories as ≥CIN2 (i.e., CIN2 or CIN3 or cancer) and ≤CIN1 (i.e., No CIN or CIN1) between reference diagnosis by expert pathologist with H&E staining and community pathologist with H&E staining and agreements for alternate CIN binary categories as ≥HSIL-histology (i.e., HSIL-histology or cancer) and ≤LSIL-histology (i.e., No CIN or LSIL-histology) between reference diagnosis by an expert pathologist with H&E + [biomarker specified in paragraph (b)(1)(i) of this section] and a community pathologist with H&E + [biomarker specified in paragraph (b)(1)(i) of this section] must be evaluated and compared, as applicable.(G) The staining performance of the device as determined by the community pathologists during review of the study slides must be evaluated. The staining performance criteria assessed must include overall staining acceptability, background staining acceptability, and morphology acceptability, as applicable.
(H) Appropriate training requirements for users, including interpretation manual, as applicable.
(I) Identification of risk mitigation elements used by the device, including a description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing.
(2) The device's 21 CFR 809.10(b) compliant labeling must include a detailed description of the protocol, including the information described in paragraph (b)(1)(ii) of this section, as applicable, and a detailed description of the performance studies performed and the summary of the results, including those that relate to paragraph (b)(1)(ii) of this section, as applicable.

Summary

0

EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR CINtec Histology

DECISION SUMMARY

A. DEN Number:

DEN160019

B. Purpose for Submission:

De Novo request for evaluation of automatic class III designation of the CINtec Histology device

C. Measurand:

p16™K4a protein

D. Type of Test:

Immunohistochemistry, qualitative

E. Applicant:

Ventana Medical Systems, Inc.

F. Proprietary and Established Names:

CINtec Histology

G. Regulatory Information:

1. Regulation section: 21 CFR § 864.1865
1. Classification: Class II (special controls)
1. Product code:

PRB

1. Panel:

1

H. Indications for use:

1. Indications for use:

CINtec Histology is a qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4. and is intended for use in the light microscopic assessment of the p16thK4a protein in formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues using OptiView DAB IHC Detection Kit on a VENTANA BenchMark ULTRA instrument. The test is indicated as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN). Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information.

2. Special conditions for use statement(s):

For in vitro diagnostic (IVD) use only

For prescription use only

3. Special instrument requirements:

VENTANA BenchMark ULTRA instrument

I. Device Description:

The CINtec Histology test is a single dispenser IHC assay system comprised of an anti-p16 primary antibody optimized for use with the BenchMark ULTRA automated slide staining instrument and the OptiView DAB IHC Detection Kit. The antibody is diluted in a Tris-HCl buffer containing carrier protein and 0.1% ProClin 300 as a preservative, and provided as a ready-to-use liquid in a FloLock dispenser. CINtec Histology is available in a 50 test size and a 250 test size.

The OptiView DAB IHC Detection Kit (OptiView) is an indirect, biotin-free system for detecting mouse IgG, mouse IgM, and rabbit primary antibodies and is comprised of 6 dispensers packaged together in one box. The components of the OptiView DAB IHC Detection Kit are as follows:

Component	Content
OptiView Peroxidase
Inhibitor	3.0% hydrogen peroxide solution.
OptiView HQ Universal
Linker	Cocktail of HQ-labeled antibodies (goat anti-mouse IgG, goat anti-mouse IgM and goat anti-rabbit) ( 0.5). The study confirmed specificity of the anti-p16 mK40 (E6H4) primary antibody to only its immunizing peptide.

iii. Immunoreactivity:
Analytical specificity and sensitivity were determined by staining a variety of normal and neoplastic human tissues with the CINtec Histology. For the purposes of this study, any nuclear and/or cytoplasmic staining was considered as positive staining, unless otherwise specified. Many normal tissues demonstrated staining of a few cells or specific cell types as noted. This may be expected due to the role of the p16 mK4a protein in cell cycle regulation. No unexpected staining was observed with the CINtec Histology on the normal and neoplastic tissues.

| Tissue | #
Positive
/ Total
cases | Cell Type |---------------------------|----- | Cerebrum | 1/3a,b | Cerebellum | 3/3 | Adrenal gland | 3/3a | Ovary | 2/2a | Pancreas | 3/3c | Tissue | #
Positive
/ Total
cases | Cell Type | Parathyroid
gland | 1/1 | Hypophysis | 3/3 | Testis | 2/3c | Thyroid | 2/5c | Breast | 3/3 cells, and stromal cells |
| Spleen | 3/3a | Tonsil | 3/3a lymphocytes and follicular cells |
| Endometrium | 2/3a | Skeletal
muscle | 0/3 | Nerve (sparse) | 1/3a | Thymus | 1/3a | Myeloid (bone
marrow) | 0/3 | Lung | 0/4 | Heart (cardiac
muscle) | 0/3 | Esophagus | 0/3 | Stomach | 0/3 | Small intestine | 3/3a | Colon | 3/3a | Liver | 2/3c | Salivary gland | 2/3a | Kidney | 0/3 | Prostate | 0/3 | Cervix | 2/3a | Tissue | #
Positive
/ Total
cases | Cell Type | Skin | 0/2 | Mesothelium | 0/2 |
------------------------------|-----------------------------------------------------------------------------|
| Glial cells |
| Purkinje cells |
| Adrenocortical epithelial cells |
| Stromal cells and endothelial cells |
| Acinar cells |
|
| Chief cells |
| Anterior pituitary epithelial cells |
| Spermatogenic and Leydig cells |
| Follicular and parafollicular cells |
| Myoepithelial cells, luminal epithelial
| Lymphocytes, follicular dendritic cells |
| Squamous epithelial cells,
dendritic
| Stromal cells |
| No specific staining |
| Schwann cells |
| Epithelial reticular cells |
| No specific staining |
| No specific staining |
| No specific staining |
| No specific staining |
| No specific staining |
| Lymphocytes |
| Lymphocytes and plasma cells |
| Hepatocytes |
| Striated duct epithelial cells |
| No specific staining |
| No specific staining |
| Stromal cells and endocervical cells |
|
| No specific staining |
| No specific staining |

Table 8: CINtec Histology staining in FFPE normal tissues

14

15

4 few cells staining; 8 nuclear staining only; 8 cytoplasmic staining only

	Table 9: CINtec Histology staining in a variety of FFPE neoplastic tissues
	t and and the province of the first of the first of the first of the first of the first of the first of the first of the first of the first of the first of the first of the f

| Neoplasm | # Positive /
Total cases | Neoplasm | # Positive /
Total cases |
|--------------------------------------------------|-----------------------------|---------------------------------------------|-----------------------------|
| Glioblastoma | 1/1 | Hepatocellular
carcinoma | 0/1 |
| Atypical meningioma | 0/1 | Hepatoblastoma | 0/1 |
| Malignant ependymoma | 1/1 | Renal clear cell
carcinoma | 0/1 |
| Malignant
oligodendroglioma | 0/1a | Prostatic
adenocarcinoma | 1/2 |
| Ovarian Serous papillary
adenocarcinoma | 1/1 | Leiomyoma | 1/1 |
| Ovarian adenocarcinoma | 0/1 | Uterine endometrial
adenocarcinoma | 1/1 |
| Islet cell carcinoma | 0/1 | Uterine endometrial
clear cell carcinoma | 1/1a |
| Pancreatic
adenocarcinoma | 0/1 | Cervical squamous cell
carcinoma | 2/2 |
| Seminoma | 0/1 | Embryonal
rhabdomyosarcoma | 1/1 |
| Embryonal carcinoma | 0/1 | Malignant melanoma | 1/1 |
| Thyroid Medullary
carcinoma | 1/1 a,b | Basal cell carcinoma* | 1/1 |
| Thyroid Papillary
carcinoma | 0/1 | Squamous cell
carcinoma | 0/1 |
| Breast intraductal
carcinoma | 1/1 | Neurofibroma | 0/1 |
| Breast invasive ductal
carcinoma | 2/2 | Neuroblastoma | 0/1 |
| Neoplasm | # Positive /
Total cases | Neoplasm | # Positive /
Total cases |
| Diffuse B-cell lymphoma | 1/3 | Epithelial malignant
mesothelioma | 1/1 |
| Lung small cell
undifferentiated
carcinoma | 1/1 | Hodgkin lymphoma | 1/1 |
| Lung squamous cell
carcinoma | 0/1 | Anaplastic large cell
lymphoma | 1/1 |
| Lung adenocarcinoma | 1/1 | Bladder transitional cell
carcinoma | 0/1 |
| Esophageal squamous cell
carcinoma | 0/1 | Low grade
leiomyosarcoma | 1/1 |
| Esophageal
adenocarcinoma | 0/1 | Osteosarcoma | 1/1 |
| Gastric mucinous
adenocarcinoma | 1/1 | Spindle cell
rhabdomyosarcoma | 1/1 |
| Gastrointestinal
adenocarcinoma | 3/3 | Intermediate grade
leiomyosarcoma | 1/1 |
| GIST | 3/3 | | |

16

ª few cells staining; b nuclear staining only

f. Robustness:

i. Tissue Thickness:
Robustness of staining performance due to tissue thickness was evaluated using 3 unique human cervical cases (cervical carcinoma, CIN1, and normal cervix). Tissues were sectioned and tested in duplicate at 3, 4, 5, 6, and 7 microns. Results for all samples were compared to the recommended 4 micron thickness. All tissue thicknesses demonstrated appropriate specific staining and background levels with CINtec Histology.

ii. Fixation:

The impact of pre-analytical factors (fixation type and fixation time) on the p16 mK4 antigen as detected by the CINtec Histology was assessed using fresh xenograft tumors derived from cancer cell line. Tumors were fixed for 1 hour, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours and 72 hours with each of the following fixatives: 10% neutral buffered formalin (10% NBF), zinc formalin, alcohol formalin, alcohol formalin acetic acid (AFA), Prefer solution and Z-fix. The resulting fixed tissues were paraffin embedded, then sectioned and stained with the CINtec Histology. Slides were read by a single reader and scored for p16 staining intensity and background. Results for all fixation types and times were

17

compared to those for tissues fixed for 12 hours with 10% NBF. Tissues fixed in 10% NBF, zinc formalin, and Z-Fix across all seven fixation times performed equivalently to tissue fixed in 10% NBF for 12 hours. It is recommended that tissues be fixed with 10% NBF for a minimum of 6 hours before staining with the ClNtec Histology device. Alcohol formalin and Prefer fixatives are not recommended for use with CINtec Histology due to demonstrated weaker or variable staining.

iii. Staining Options:
All user selectable options in the CINtec Histology staining procedure on the BenchMark ULTRA stainer were validated using 6 cervical samples (1 CIN1, 3 CIN2, 2 normal cervix) stained with all possible combinations allowed within the CINtec Histology staining procedure, for a total of 6 staining conditions. Results from each sample were compared against the recommended protocol. All samples tested for all staining conditions yielded equivalent results to the recommended condition with regard to both the CINtec Histology staining pattern and CINtec Histology positive/negative status.
1. Comparison studies:
- a. Method comparison with predicate device:

Not applicable

b. Matrix comparison:
FFPE uterine cervical punch biopsy specimen is the only recommended matrix.
1. Clinical studies:
  To demonstrate that the CINtec Histology results in an improvement in consistency of the diagnosis of cervical intraepithelial neoplasia (CIN), levels of agreement between Community pathologists' (CP) and Expert pathologists' (XP) readings of cervical punch biopsy tissue were evaluated in a clinical study. The clinical study was performed on 1,100 retrospectively collected FFPE cervical punch biopsy specimens, which represent a colposcopy referral population. An XP derived reference diagnosis was established for each study case using the hematoxylin & eosin (H&E) stained slides only and using the H&E and CINtec Histology stained slides. Study slides were assessed by CPs reviewing H&E stained slides only in the first round (Round 1, CP1) and by reviewing H&E and CINtec Histology stained slides in the second round (Round 2, CP2) for each study case by same pathologists after a 4-week washout period. The results were compared to XP diagnosis for each study case to evaluate positive, negative and overall agreements. Two XPs established their independent diagnoses [No CIN, CIN1, CIN2, CIN3, adenocarcinoma in situ (ACIS), or invasive carcinoma] based on the H&E-stained slides for each of the 1,100 cases. The pathologists were also provided with the following clinical information: patient age. Pap cytology result and HPV test result (if available). Discordant cases were evaluated by a third XP. Cases for which a 2 out of 3 majority diagnosis was not achieved were reviewed during an adjudication review meeting that

18

included all three XPs. Majority (or consensus) results established the Expert-derived Reference Diagnosis for each case evaluated in the study. After a minimum of 4 week washout period, the same XPs evaluated both the H&E and CINtec Histology slides to establish their diagnosis (No CIN, LSIL-histology, HSIL-histology, (ACIS, or invasive carcinoma). The process of establishing the majority diagnoses was that used for establishing the Reference Diagnosis on H&E-stained slides only.

Seventy (70) Board Certified CPs, from across the United States, participated in the study. In the first round (Round 1, CP1), the 1,100 H&E-stained cases were divided into 4 reading sets of 275 cases with comparable distributions of individual diagnostic categories per Reference Diagnosis. The 70 CPs were assigned to 4 groups consisting of either 17 or 18 pathologists per group. For each case within their assigned reading set, the pathologists were provided with the following clinical information: patient age, Pap cytology result and HPV test result (if available). The CPs independently rendered their diagnoses on the H&E-stained slide for each of their assigned cases (No CIN, CIN1, CIN2, CIN3, ACIS, or invasive carcinoma). In addition, CPs were asked during Round 1 reading whether they would request an adjunctive p16 IHC stain (CINtec Histology) in alignment with the following criteria from the LAST recommendations ': 1) the H&E morphologic differential diagnosis is between pre-cancer (CIN2 or CIN3) and a mimic of pre-cancer; 2) the H&E morphologic diagnosis is CIN2; or 3) the H&E morphologic diagnosis is 1 Darragh TM, Colgan TJ, Cox JT, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med - Vol 136. October 2012

19

| | | Reference Diagnosis =
Majority/Consensus Diagnosis by Expert Panel
H&E Only | | | | | Total |
|------------------------------------------------------------------------------------------------------|--------------------|-----------------------------------------------------------------------------------|------|------|------|-------------------|-------|
| | | No
CIN | CIN1 | CIN2 | CIN3 | ACIS or
Cancer | |
| Reference
Diagnosis =
Majority/
Consensus by
Expert Panel
H&E and CINtec
Histology | No CIN | 175 | 4 | 4 | 0 | 0 | 183 |
| | LSIL-
histology | 15 | 61 | 4 | 1 | 0 | 81 |
| | HSIL-
histology | 24 | 29 | 79 | 37 | 0 | 169 |
| | ACIS or
cancer | 0 | 0 | 0 | 0 | 3 | 3 |
| Total | | 214 | 94 | 87 | 38 | 3 | 436 |

Table 10: XP Agreement, H&E only vs. H&E and CINtec Histology (LAST Cases)

The levels of agreement between CPs using H&E alone vs. the Reference Diagnosis by XPs using H&E alone and agreements between CPs with H&E and CINtec Histology vs. the Reference Diagnosis by XPs with H&E and CINtec Histology are presented in Table 11 below.

Table 11: CP Agreement with Reference Diagnosis, H&E only vs. H&E+CINtec histology (LAST Cases)

	H&E Only				H&E and CINtec Histology
	Reference Diagnosis =
Majority/Consensus Diagnosis by
Expert Panel				Reference Diagnosis =
Majority/Consensus Diagnosis by Expert
Panel
	No CIN	CIN1	CIN2	≥CIN3	No CIN	LSIL-
histology	HSIL-
histology	ACIS
or
Cancer
Number of cases	214	94	87	41	183	81	169	3
Percent of cases with
CP majority
diagnosis the same as
Reference Diagnosis	29.0%
(62/214)	73.4%
(69/94)	72.4%
(63/87)	53.7%
(22/41)	39.3%
(72/183)	72.8%
(59/81)	96.4%
(163/169)	66.7%
(2/3)
Number of CP with
diagnosis the same as
CP majority averaged
over all cases	10.5	11.8	10.6	10.1	11.3	12.6	14.8	16.5

20

| | H&E Only
Reference Diagnosis =
Majority/Consensus Diagnosis by
Expert Panel | | H&E and CINtec Histology
Reference Diagnosis =
Majority/Consensus Diagnosis by Expert
Panel | |
|--------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|-------------------|------------------------------------------------------------------------------------------------------|--------------------|
| | ≤CIN1 | ≥CIN2 | ≤LSIL-histology | ≥HSIL-histology |
| Number of cases | 308 | 128 | 264 | 172 |
| Percent of cases with
CP majority
diagnosis the same as
Reference Diagnosis | 42.5%
(131/308) | 66.4%
(85/128) | 49.6%
(131/264) | 95.9%
(165/172) |
| Number of CP with
diagnosis the same as
CP majority averaged
over all cases | 11.2 | 10.5 | 11.9 | 14.8 |

The estimate of positive percent agreement (PPA) was based on the comparison of the agreement between CPs using H&E and CINtec Histology vs. Reference Diagnosis by XPs using H&E and CINtec Histology for cases with reference diagnoses of ≥HSILhistology and the agreement between CPs using H&E vs Reference Diagnosis by XPs using H&E for cases with reference diagnoses of ≥CIN2. The estimate of negative percent agreement (NPA) was based on the comparison of the agreement between CPs using H&E and CINtec Histology vs. Reference Diagnosis by XPs using H&E and CINtec Histology for cases with reference diagnoses of