Role of Ultrasound in Cervical Cancer Assessment

Abstract

Cervical cancer is a common gynecological cancer worldwide. The use of imaging modalities for pre-treatment workups for cervical cancer is growing. Ultrasound is less expensive, faster, and more generally available than other imaging modalities for the evaluation of cervical cancer. It is also a portable imaging radiological imaging modality. The clinical application of ultrasonography in cervical cancer has been improved by sophisticated ultrasonography techniques. Ultrasound provides very precise information on the presence of tumors and the extent of localized tumors. It is also important for precise preoperative staging and assessing treatment response. In this chapter, the role of ultrasound in assessing cervical cancer will be discussed.

1. Introduction

Cervical cancer is a frequent gynecologic malignancy in women. In terms of both incidence and death, it ranks fourth in global cancer statistics for 2018. About 90% of the 342,000 cervical cancer-related deaths took place in low- and middle-income nations. South-East Asia, Central America, and Sub-Saharan Africa (SSA) have the greatest incidence and fatality rates of cervical cancer [1]. The updated 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system includes imaging and pathology assessments for cervical cancer [2].

Cervical cancer pre-treatment work-up is using more and more imaging modalities [3]. To create treatment plans, imaging modalities like positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) were used. However, these services are expensive, not readily available everywhere, especially in low-income nations, necessitate the administration of intravenous contrast media, take a long time to scan, and are not real time [4].

Nonetheless, in recent years, ultrasonography has gained popularity as an imaging method for examining women with cervical cancer [5]. In comparison to other imaging techniques for the evaluation of cervical cancer, ultrasound is faster, radiation-free, less expensive, non-invasive, does not need a contrast agent, and is more readily available [6]. Furthermore, modern ultrasound technology has advanced in recent decades, and image quality has improved. High-frequency transvaginal and transrectal ultrasound, when the probe is placed close to the tumor, can produce detailed images of the cervical tumor [6]. This chapter attempted to present the role of ultrasound in cervical cancer assessment.

2. Cervical cancer screening with ultrasound

Using three-dimensional (3D) power Doppler ultrasound indices, the characteristics of cervix blood flow in normal women and women with precancerous lesions or invasive cancers were reported, comprising blood flow and vascularization as well as the number of vessels in the volume of interest and the flow intensity at the time of volume acquisition [7]. Enhancing ultrasound-based cervical cancer screening could be important, especially for women who are fertile. This would help reduce the unnecessary use of cervical biopsy or conization treatments [4].

3. Cervical cancer: local staging

A comprehensive evaluation to determine the extent of cervical cancer should be performed if the diagnosis has been identified. Several investigations were conducted to detect the spread of cervical cancer lesions.

3.1 Transvaginal/transrectal ultrasound for local staging of cervical cancer

The use of ultrasound for cervical cancer staging was first described in the early 1990s [8].

Transrectal ultrasound (TRUS) reliability for cervical cancer staging was previously documented [9]. Innocenti et al. compared clinical staging to transrectal ultrasonography in a group of 124 women diagnosed with cervical cancer. TRUS was found to be more sensitive (78%) than clinical exams (50%) for detecting parametrial infiltration. The sensitivity, specificity, and accuracy of TRUS for the extent of parametrial involvement were 78%, 89%, and 87%, respectively [9].

TRUS and MRI were compared in early-stage cervical carcinoma by Fischerova et al. [10]. In a group of 95 cases, they found that TRU was more sensitive than MRI for detecting parametrial involvement (83% vs. 50%) and was able to more clearly detect tiny cervical tumors (1 cm) [11].

In a study employing histology as the gold standard, Gaurilcikas et al. evaluated TVS’s capacity to define the location and quantify the size of early cervical cancer [12]. There was a strong connection.

The outcomes of a recent European multicenter trial comparing TVS and MRI for defining cervical malignancy were published by Epstein et al. These findings demonstrated that TVS was superior to MRI in both women who underwent a cone biopsy prior to surgery and those who did not [13].

A prospective study [14] focused on the diagnostic abilities of TVUS and MRI for determining the presence and extent of cervical cancer. Those with locally advanced cervical cancer scheduled surgery following neoadjuvant therapy, while those with early-stage cervical cancer planned for main surgery. The presence of the tumor was detected by TVUS or MRI in 56/60 (93%) and 53/60 (88%) patients, respectively. With regard to the parameters examined, such as the detection of the depth of stromal invasion to be greater than two-thirds, both ultrasonography and MRI exhibited equivalent sensitivity and specificity. The inexpensive cost and ubiquitous availability of ultrasound make it superior to MRI [14].

3.2 Three-dimensional ultrasound (3DUS) scan

The size of the tumor plays a key role in determining a patient’s prognosis for cervical cancer. A 3D ultrasound system was reported to have computed the true volume of cervical cancer more precisely than a 2D ultrasound system [15].

The study, which involved 14 cervical cancer patients who got transvaginal volume ultrasound examinations before surgery, showed that three-dimensional multiplanar sonography is a promising method for the local staging of cervical cancer. The results of 3D ultrasonography were consistent with pathology in 12 of the 14 instances [16].

In a series of 24 women with cervical cancer, Byun et al. compared 3DUS, MRI, clinical exam, and surgical staging [17]. According to their findings, 3DUS had a higher accuracy rate (67%) than the pelvic exam (62%) and MRI (41%).

In a recent study, local staging of cervical cancer was reported for 46 patients who had pelvic MRIs and high-resolution transvaginal ultrasound (TVUS) scans [18]. The analysis of the tumor volume in both early-stage and late cervical cancers revealed a significant association between TVUS and MRI. A useful and affordable imaging technique for local cervical cancer staging is ultrasound [18].

The stage of invasive cervical cancer was determined by three-dimensional transvaginal ultrasonography (3D-TVUS), which was then compared to MRI for locally advanced cervical cancer [17]. TVUS had a sensitivity of 75%, MRI had a sensitivity of 75%, and clinical exanimation had a sensitivity of 25%. TVUS had a specificity of 90%, MRI had a specificity of 55.6%, and TVUS had an accuracy of 87.5%. According to the authors, preoperative 3D-TVUS may prove to be a very effective method for evaluating cervical cancer that has already spread locally [17].

4. Ultrasound findings as prognostic factors

Angiogenesis has been demonstrated to be an independent prognostic factor and to predict recurrence in cervical cancer [19, 20]. Using transvaginal Doppler ultrasound, tumor angiogenesis can be evaluated in vivo and non-invasively [21].

4.1 Transvaginal color doppler in cervical cancer

Transvaginal Color Doppler in cervical cancer allows non-invasive assessment of tumor angiogenesis.

Hsieh et al. published a paper in 1995 [22] that examined the intratumoral arteries in cervical cancer. Transvaginal color Doppler sonography was used by these authors to determine that 46.2% of cervical tumors showed blood flow color signals. When compared to individuals with no discernible color signals, they found that lymph node involvement was more common in those with detectable color signals (33% vs. 5.7%), and this was similarly correlated with a higher cell proliferation index.

For the in vivo evaluation of angiogenesis in patients with cervical cancer, Cheng et al. reported the development of a novel vascular index (VI) [23]. They used transvaginal power Doppler ultrasound to assess 35 patients with stage Ib-IIa cervical cancer, and they used image processing software to create a vascular index for each tumor. It was found that the probability of pelvic lymph node metastases increased with a higher vascular index, deeper stromal invasion, and a higher incidence of lymphovascular space invasion. In order to evaluate intratumoral vascularization in 35 women with cervical cancer and 30 healthy women, Wu et al. compared color and power Doppler [24]. They discovered that color signals were present in 97% of malignancies and that patients with cervical cancer had considerably lower levels of both PI and a vascular ratio (defined as the cross-sectional area of intratumoral arteries divided by the cross-sectional area of the tumor). Given that the vascular ratio provided more sonographic features among the various sub-classifications of cervical cancer, they came to the conclusion that power Doppler angiography was more beneficial than color Doppler.

According to Alcazar et al., tumor blood flow as measured by transvaginal color Doppler was linked with some tumor features in 100% of cases of cervical cancer. Squamous cell malignancies, moderately or poorly differentiated lesions, and advanced-stage tumors all had increased levels of tumor vascularization [25].

With contentious findings, some investigations assessed the function of the three-dimensional power Doppler in cervical cancer. In a group of 74 cervical cancers, Testa et al. [26] found no association between 3D-derived vascular indices and clinic-pathological characteristics. However, 141 women with early-stage cervical cancer were studied using 3D Power Doppler, and Hsu et al. have presented their findings. They found blood flow in 85% of the tumors and discovered a correlation between tumor volume and tumor vascularization [27]. On the other hand, Alcazar et al. [28], Tanaka and Umesaki [29], and Belitsos et al. [7] found a correlation between specific tumor features, such as tumor stage and histologic grade, and tumor vascularization as determined by 3D power ultrasound.

5. Ultrasound for therapy response prediction

Several studies have been conducted to assess the role of ultrasound in predicting treatment response in women with cervical cancer.

5.1 Prediction of neoadjuvant chemotherapy response

Utilizing 3D Power Doppler Ultrasound, researchers examined the usefulness of transvaginal ultrasound in the early prediction of the pathological response in a large series of patients with locally advanced cervical cancer who underwent major surgery followed by neoadjuvant chemotherapy. The study included 88 of the 108 patients. Patients with a partial response showed significantly larger tumor volumes after 2 weeks of neoadjuvant treatment than those with a complete response. The partial response group had a lower vascularization index (VI) before and after 2 weeks of treatment than the complete response group [30].

The use of the Power Doppler vascularity index (PDVI) to predict response to neoadjuvant chemotherapy (NACT) in bulky early-stage cervical cancer was described. A transvaginal power Doppler was used to evaluate the response to NACT in 25 women with bulky early-stage cervical carcinoma treated with NACT followed by surgery. Twelve (48%) individuals responded to NACT, while thirteen (52%) remained stable or had worsening disease after NACT [31].

42 cervical cancer patients who were referred for NACT and had locally progressing disease participated in a prospective trial. Women with locally advanced cervical cancer had TRUS and MRIs to determine the size of their tumors after neoadjuvant treatment. For patients with cervical cancer undergoing neoadjuvant chemotherapy (NACT), TRUS may be a reliable diagnostic tool for assessing tumor volume [32].

5.2 Response to neoadjuvant chemotherapy and radiation prediction

Using 2D ultrasound parameters, 3D power Doppler, or contrast-enhanced indices, patients with locally advanced cervical cancer who underwent radical surgery after chemoradiation were assessed for the remaining tumor [33]. The results showed that in patients with locally advanced cervical cancer, grayscale and color Doppler ultrasonography perform poorly as a diagnostic tool for identifying disease that persists following neoadjuvant chemotherapy and radiation [33].

Two investigations were carried out by Alcazar et al. [34, 35] to evaluate the function of transvaginal color Doppler in predicting the clinical and pathological response to chemoradiotherapy in cases of locally advanced cervical cancer. They discovered that malignancies with fewer blood vessels responded more favorably than those with more.

5.3 Radiotherapy response prediction

Grayscale and color Doppler ultrasonography were used to assess the treatment response in cervical cancer patients [36]. Thirteen patients with advanced stages of cervical cancer were included in this study. Six months prior to and six months following radiation therapy, the patients underwent transvaginal color Doppler ultrasound and MRI exams. A complete response to treatment was significantly correlated with greater resistance indices. There was a substantial association between the MRI findings and resistive indices. The characteristics obtained with transvaginal color Doppler ultrasonography could be a useful alternative to MRI in evaluating the response of cervical cancer to treatment [36].

5.4 Response to concurrent chemoradiation

Transvaginal color Doppler sonography has been shown to be beneficial in predicting clinical response to concomitant chemoradiation for locally advanced cervical cancer [35]. There were 21 individuals with locally advanced cervical cancer in the study. Before starting concurrent chemoradiotherapy, the patients had their tumor vascularity assessed with TVCD. The metrics included the lowest pulsatility index (PI), lowest resistance index (RI), and highest peak systolic velocity (PSV) from intratumor central vessels [35]. Complete clinical response (CR) was achieved in 11 patients (52%), while partial clinical response (PR) was reached in 10 patients (48%). PI was higher in CR tumors than in PR cancers; RI was higher in CR tumors than in PR tumors. In PSV, no differences were discovered.

5.5 Ultrasound in intraoperative guidance

A recent retrospective study explored the role of intraoperative ultrasonography guidance in intracavitary brachytherapy for cervical cancer. Ultrasound guidance was used for tandem selection and proper application. Intracavitary brachytherapy was performed under ultrasound guidance for 412 insertions in 113 cervical cancer patients. One of the 113 patients treated with ultrasound guidance had uterine perforation, one had tandem myometrium, and one had a short tandem length. Intraoperative sonographic guidance improved the efficiency of intracavitary brachytherapy for cervical cancer and reduced perforation rates [37]. The earlier study, which involved intraoperative ultrasonography guidance during intracavitary brachytherapy applicator placement for cervical cancer patients, yielded similar outcomes [38]. Intraoperative ultrasonography guidance enhanced the success rate of applicator placement [38].

6. Conclusion

Accurately identifying the extent of the tumor and choosing the best course of therapy for patients with cervical cancer depend on the imaging performed during the basic diagnostic work-up. In cervical cancer, sonography could be a valuable technique for assessing the local extent of the illness. This approach is only useful for determining the status of lymph nodes. Doppler ultrasonography tumor vascularization could be used to monitor and predict response to therapy. Including ultrasound examination in cervical cancer screening, staging, and predicting therapy response plays a significant role, particularly in low-income countries where advanced imaging modalities are not available.

Conflict of interest

The authors have declared that no competing interest exists.