**3.1 ThinPrep integrated imager system mirror inspection support system**

In Japan, the cervical cancer screening uptake rate is lower than in Europe and the USA. In addition to improving the uptake rate, training cytologists for screening have

#### *Cytological Evaluation DOI: http://dx.doi.org/10.5772/intechopen.109886*

become an issue [25–27]. In Europe and the USA, the introduction of liquid-based cytology (LBC) and automatic screening support devices with artificial intelligence (AI) has been progressing to support the high cervical cancer screening uptake rate. Such automatic screening support devices are expected to become widespread in Japan in the future. When one hears the term "automated screening support system,"

#### **Figure 8.**

*ThinPrep® integrated imager. Marketing authorization number; 13B1X10179001003.*

one may wonder if it is safe. However, when a cytotechnologist performs the screening, it is undertaken by a human, which entails the risk of oversight and other issues. The concept of this system is to avoid overlooking high-grade squamous intraepithelial lesion (HSIL) lesions.

The system performs two ThinPrep smears for each case. One of them is stained using ThinPrep stain, a staining solution that differs from the usual Papanicolaou stain. The ThinPrep-stained specimens are then set in the machine in advance and

**Figure 10.**

*Manual screening vs. integrated imager screening (I2 screening). (a) M screening: LSIL histology: HSIL/CIN3. (b) I2 screening: HSIL histology: HSIL/CIN3. (c) M screening: Lost histology: HSIL/CIN.*

read through, and 22 areas that need to be checked again are selected. These areas are checked with the cytologist using the special microscope shown in **Figure 8** to make a final determination (see **Figure 9**).

This machine (special microscope) shown in **Figure 10** is available from Hologic. A comparison of actual cytologist specimens (M-microscopy) and I2-microscopy (machine) is also shown (see **Table 3**).

ThinPrep-stained specimens appear very dark compared with the normal Papanicolaou stains. However, many of the cells with some atypia have increased chromatin, so they are not likely to be observable by eye unless they are stained somewhat darkly.

The machine then identifies atypical cells at a certain percentage of sensitivity without tiring, unlike humans. In the near future, Japan's aging population is expected to become a serious issue, and this and other factors will increase the need to rely on machines.

However, the author believes that this system would not be effective unless we can make an accurate judgment by looking at the cells presented by this special


*Agreement rate with tissue diagnosis: LSIL.*

*M screening: 95.0%.*

*I2 screening: 97.5%.*

*Agreement rate with tissue diagnosis: HSIL or higher.*

*M screening: 60.0%*

*I2 screening: 86.6% 26.6% up!*

*Notes)*

*M screening: Manual screening. I2 screening: Integrated Imager screening. Quoted from reference [26], partially modified. Materials from department of Pathology, Osaka Police Hospital and Hologic, Inc.*

#### **Table 3.**

*Comparison of M screening and I2 screening with Histology.*

microscope. It may be meaningless unless the cytologist has the skills to make accurate judgments when presented with several fields of view.

Although Hologic's system requires the preparation of LBC specimens, other companies have developed and marketed systems that allow the use of conventional smears. However, it is assumed that it is quite difficult to create a database based on the conventional method. The system is actually being used by a major testing company, and it is assumed that a considerable number of specimen images are being compiled into a database before it can be used in the current system.

#### **3.2 Combination with HPV testing**

HPV testing can now be performed on the same vial from which the LBC specimen is taken for the purpose of cytological diagnosis testing. HPV detection reagents are available from Qiagen, Roche, and BD [28–30]. This seems to be an excellent system for the early detection of dysplastic lesions and the eradication of cervical cancer from both the polymerase chain reaction data and the morphology on the cytogram. In addition, HPV vaccination, which had been on the decline because of adverse reactions, has been actively resumed in Japan.
