The incidence and mortality of cervical cancer ranks as the fourth malignant tumor in women worldwide [1, 2]. Persistent infection with high-risk human papillomavirus (hrHPV) is the main cause of cervical cancer [3, 4]. Approximately 90% of cervical cancers occur in underdeveloped or developing countries with inadequate screening or lack of human papillomavirus (HPV) vaccination [5]. Early diagnosis and accurate staging are the basis for a good prognosis. At present, the diagnosis of cervical cancer is mainly through cervical cell scraping, and hrHPV testing, colposcopy, and pathological biopsy of the cervix and endocervical canal [6]. However, the coverage of cervical cancer screening and HPV vaccination is insufficient in China. Therefore, it is necessary to seek an economical, non-invasive and convenient auxiliary examination method, so as to timely remind clinicians to screen patients for cervical cancer.

Study has demonstrated that the elastography software installed on the ultrasound scanner can greatly improve the detection accuracy of ordinary ultrasound technology, increase its clinical application value and significantly improve the accuracy of disease diagnosis [7]. Shear wave elastography (SWE) is a kind of elastography, which is a new form of real-time dynamic elastography technology [8]. It can achieve real-time imaging and has good image quality. It displays tissue elastography in real time by color coding technology, where red indicates hard tissues, green indicates moderately stiff tissues and blue indicates softer tissues [9]. These are quantified as Young’s modulus (elastic modulus) values in kilpoascal (kPa), so this technique utilizes use numerical values to describe the hardness differences between tissues [10]. Pathological changes, such as the presence of tumors or inflammation, alter the composition and structure of the tissue and increase the stiffness of the diseased tissue [11]. The cervical tissue is of medium hardness, and in the presence of cervical cancer, the cervical tissue becomes significantly hard, allowing hardness to be one of the characteristics to distinguish benign and malignant cervical lesions [12]. SWE technology quantifies the hardness of cervical tissue by using Young’s modulus value [13], which is a form of quantitative elastography in real terms and has the advantages of being objective, economic, non-invasive, non-radiation, real-time dynamic and repeatable [14].

This study utilized SWE technology to detect cervical stiffness of the subjects and provide a quantitative evaluation index, in order to explore the application value of this objective, economical, convenient and non-invasive examination technology for patients with cervical cancer. This technique may contribute to the screening of cervical cancer, and provide a new reference index for assisting cervical cancer screening. Second, the relationship between cervical tissue stiffness and clinicopathological factors in patients with cervical cancer was further analyzed, and the value of SWE technology in clinical staging and treatment of cervical cancer was explored.

In 2010, Sebag et al. [16] first reported the use of SWE in the diagnosis of thyroid cancer, which made quantitative assessment of tissue stiffness possible. With different hardness, the quantitative value of elasticity is different. SWE technology is a major advance of ultrasound elastography technology, which can directly quantify the tissue hardness with the results being more objective [12]. At present, SWE, as a quantitative examination technique, analyzes tissue stiffness by measuring the elastic modulus value of tissue, and is widely used in the screening and efficacy evaluation of thyroid cancer [17], breast cancer [18], prostate cancer [19, 20] and other tumors. Some scholars have pointed out that elastography improves the ability of ultrasound to differentiate benign and malignant breast lesions, thereby reducing the number of biopsies of benign breast nodules [21].

SWE technology has potential in the research of cervix pathology, and its non-invasiveness and repeatability are favored by clinicians [22, 23]. Regarding repeatability, relevant studies have pointed out that it is affected by the expertise of the examiners, especially as some experience is required to obtain reproducible results [24, 25]. It is currently believed that if performed by an experienced sonographer, ultrasound can provide the same diagnostic accuracy as magnetic resonance imaging (MRI) [26]. How to overcome the differences in measurement values between different machines and different sonographers may be a further difficulty to be overcome in the future clinical application of this examination technology. For accuracy, it is necessary to improve the machine measurement and strengthen the training of sonographers.

In this study, it was found that the maximum, minimum and mean elastic modulus of the cervical cancer group were significantly different from those of the cervicitis group and the CIN group (p 0.001), and the value of the cervical cancer group was significantly higher than that of the cervicitis group and the CIN group. The results suggest that SWE technology has good clinical application value in the detection of cervical cancer. We speculate that the clinical application of this economical and convenient technology to the cervix can expand the screening scope of cervical cancer in economically underdeveloped areas, remind clinicians to be more vigilant in the targeted screening of cervical cancer, and have research and application value for the early detection, early diagnosis and treatment of cervical cancer.

Taking pathology as the gold standard, this study evaluated the application value of SWE technology in cervical cancer and determined its accuracy. In this study, the area under the ROC curve of the mean value was the largest, followed by the maximum value, and the minimum value being the smallest. For the commonly used indicators of accuracy evaluation, the positive likelihood ratios of the mean, maximum and minimum values were 21.74, 19.97 and 3.89, respectively, and the negative likelihood ratios of the mean, maximum and minimum values were 0.18, 0.25 and 0.22, respectively. Based on statistics, it is generally believed that the positive likelihood ratio $>$10 indicates that the diagnostic test has a relatively strong ability to confirm the disease, while the negative likelihood ratio being less than 0.1 is considered that the diagnostic test has a relatively strong ability to exclude the disease. In conclusion, the mean and maximum value of the elastic modulus have a higher ability to detect the disease and a higher ability to exclude the disease. When SWE technology is actually applied in clinical practice, the mean and maximum value of elastic modulus can be clinically useful.

The optimal cut-off point of the maximum elastic modulus was 82.2 kPa, with a sensitivity of 75.9% and a specificity of 96.2%. The optimal cut-off point of the mean value of elastic modulus was 66.5 kPa, with a sensitivity of 82.8% and a specificity of 96.2%. Clinically, if the best diagnostic cut-off point was used as the cut-off value to diagnose cervical cancer, compared with the original data and patient data, we found that the maximum value was less than 82.2 kPa in 3 patients with cervical cancer, and the mean value was less than 66.5 kPa in 1 patient with cervical cancer. After changing the diagnostic cut-off point dynamically, changes of sensitivity and specificity could be observed. The rate of missed diagnosis decreased, but the specificity also decreased. When the cut-off point of the maximum value was 68.6 kPa, the sensitivity increased to 89.7%, and when the cut-off point of the maximum value was 62.4 kPa, the sensitivity increased to 96.6%. When the diagnostic cut-off point of the mean value decreased to 58.2 kPa, the sensitivity increased to 89.7%, and when the diagnostic cut-off point of the mean value decreased to 52.6 kPa, the sensitivity increased to 96.6% (Fig. 2). Therefore, based on an auxiliary screening examination technology, for the purpose of early detection, early diagnosis and early treatment, reducing the diagnostic cut-off point in clinical application can reduce the rate of missed diagnosis. In conclusion, we suggest that when SWE technology is applied to the clinical screening of cervical cancer patients, it may be more suitable to consider the appropriate reduction of the diagnostic cut-off point (i.e., the appropriate reduction of the elastic modulus value). Before the actual application in clinical practice, we will increase the sample size and correlation analysis to make the results more meaningful.

This study attempted to further analyze the relationship between cervical stiffness and the clinicopathological factors. The results of statistical analysis showed that there were statistically significant differences according to different FIGO stages and tumor lesion size, but there was no statistically significant difference according to pathological type. The analysis may be related to the fact that only 3 patients with cervical adenocarcinoma had complete data, so the number of cases was quite small. In the future, if we increase the sample size of patients with cervical adenocarcinoma, the estimated results may be different. As can be seen from Table 6, as the tumor lesions gradually increased, according to the tumor size ($\le$2 cm/$>$2 cm and $\le$4 cm/$>$4 cm), the elasticity value had an obvious increasing trend, and the difference was statistically significant. The 2018 FIGO staging also re-divided some stages according to the tumor size [27]. The study of SWE technology in cervical cancer also verified the rationality of the 2018 FIGO staging from the perspective of tumor size.

In addition, the significance of SWE technology in staging is also reflected in the following two points: first, with the increase of FIGO stage, the elasticity value of cervical stiffness gradually increased (Table 6), and the difference was statistically significant; second, we found that patients with advanced cervical cancer have higher SCCA values and are more likely to have LVSI positivity. As shown in Table 6, according to whether SCCA is abnormal or not, the maximum value and the minimum value are statistically significant. According to whether LVSI is positive or not, the maximum value and the mean value are also statistically significant, which further illustrates the research value of SWE technology in clinical staging. As for the exploration of SWE technology in the clinical staging of cervical cancer, we need further clinical research in order to achieve the purpose of improving the accuracy of clinical staging of cervical cancer prior to surgery and guiding clinical treatment [28].

In this study, the elastic values of 7 patients with cervical cancer were measured before and after radiotherapy. It can be seen that the elastic values after radiotherapy were significantly lower than those before radiotherapy, and the differences before and after radiotherapy were statistically significant. This supports that SWE technology also has clinical guiding significance and application value in the treatment of cervical cancer, which supports research in increasing the sample size and performing further in-depth exploration.

SWE technology has an application value in the detection of cervical cancer. The mean and maximum values have higher diagnostic accuracy. SWE technology also has potential clinical application value in the clinical staging and treatment of cervical cancer, but further studies with larger sample sizes are needed.

All SWE data measured in this paper are stored in the ultrasound room machine of our hospital, and further enquiries can be directed to the corresponding author.

LC designed the study and wrote the manuscript. PS was the primary operator of the SWE technique. XL, WD and MW participated in data collection and supervision. All authors have read and approved the final manuscript. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was approved and informed consent was adopted by the institutional review board of Affiliated Hospital of Xuzhou Medical University (number: XYFY2020-KL154-01).

This research received no external funding.

The authors declare no conflict of interest.