**5. Discussion**

The role of ultrasound in the pre-treatment evaluation of cervical cancer is well established [2,16–18]. However, some factors hinder the ultrasound evaluation of some tumor characteristics, such as lesion margins (especially the small exophytic ones), fornix involvement, and vascular patterns [9,11,19].

To the best of our knowledge, this is the first study that investigates the accuracy of VGS in the assessment of early-stage cervical cancer. VGS is an inexpensive and welltolerated ultrasound technique that can increase the image quality of cervical tumors. The acoustic windows created by saline solution results in a distance of the probe to the lesion, the distension of vaginal walls, and the exclusion of hindering factors, including vaginal collapse, bleeding, and/or mucus secretions.

Compared to histology (used as the gold standard), VGS and MRI assess the dimension of the lesion with similar accuracy. However, we found that VGS tended to overestimate the dimensions, whereas MRI underestimated them. Previous studies have reported that ultrasounds overestimate tumor dimensions [7,17]. Despite avoiding confounding factors, such as adjacent normal tissues, by using liquid distension in order to create an acoustic window, our data showed that the small difference between VGS and histology was statistically significant, while the difference between MRI and histology was not. Even if overestimating the tumor size could be better than underestimating it in oncological cases, it may compromise the opportunity for fertility-sparing surgery in selected patients.

The value of Lin's concordance in the assessment of the lesion dimensions was better between VGS and histology than MRI and histology. This is because MRI did not detect some small tumors, recorded as 0 mm in our study. Indeed, when the tumor was <2 cm, MRI was not able to identify 38.1% of the tumors. Therefore, the real detection rate of MRI was 47% (10 out of 21) versus 76.1% of VGS (16 out of 21). Hence, VGS is more sensitive than MRI in identifying small lesions. Prior studies did not find that TVUS was better than MRI in the detection of lesions <2 cm [9,20]. Only one previous study showed that TRUS was superior to MRI in the identification of very small lesions (<1 cm) [7].

As our study focuses on early-stage cervical cancers, we have limited data on fornix infiltration. Nevertheless, we found that VGS was more sensitive than MRI in excluding fornix infiltration, with an NPV of 100% and 88.9%, respectively. Recently, similar results have been reported by comparing the accuracy of histology to TVUS, MRI, and clinical examination under anesthesia [21]. TVUS can be a good method to exclude but not to predict vaginal infiltration, which is often overestimated. Probably, VGS could play a role in the assessment of more advanced stages of cervical cancer with vaginal involvement.

We confirmed that different histotypes have different echogenicities, as demonstrated in a previous report [11]. Epstein et al. found that the echogenicity/histotype correlation was statistically significant, with a hypoechoic pattern in the squamous tumor cells and an isoechoic pattern in adenocarcinoma tumor cells. In our study, squamous tumor cells were predominantly hypoechoic, while the adenocarcinoma tumor cells were hyperechoic. These differences could be explained by the changes in the echogenicity of surrounding tissues due to the acoustic windows placed between the ultrasound probe and the tumor.

As observed in previous studies [7,9,11,22], almost all tumors analyzed presented moderate or intense vascularization (96.4%). The power Doppler can be useful in the assessment of the presence and borders of the tumor, especially when the echogenicity does not help. Only two adenocarcinomas were poorly vascularized. These two cases did not present any other special characteristic; both tumors were >15 mm, and the patients did not receive prior therapy nor conization; one tumor showed > 2/3 stromal invasion and the other <2/3 stromal invasion.

Stromal infiltration is another interesting issue. Some studies reported that comparing ultrasound and MRI results with the final histology report led to high false-positive rates [8,17,18], and a prospective multicenter study found that the subjective assessment of TVUS or TRUS was better than objective measurements at predicting deep stromal invasion in patients with cervical cancer [23]. In our study, we observed a good concordance between

VGS and histology (89%), with a low false-positive rate (11%). The comparison between MRI and VGS for stromal invasion was not possible because MRI data were not available in all cases.

It is a well-known matter that the incidence of lymph node metastasis in cervical cancer depends on the stage: 2% in IA2, 14–36% in IB, 38–51% in IIA, and 47% in IIB (14). Stromal infiltration is one of the independent factors identified for the risk of lymph node metastases in patients with cervical cancers, along with age, tumor size, lymph vascular space invasion, histological grade, and type [23,24]. In our series, we found six patients (11%) with lymph node metastasis; all cases were FIGO stage IB. In these patients, the stromal invasion was >2/3 in five patients out of six at the histology of cervical specimens. VGS correctly identified four out of five tumor cases with stromal invasion >2/3. The only discordant patient had a not-usual histotype of cervical cancer (adenoid basal carcinoma), with an extension of 17 mm.
