Patients
A total of 28 consecutive patients were enrolled to this study and 54 images excluding 2 images that were insufficient images were evaluated. The mean age of the patients was 43 (range, 25−68) years, and 2 patients showed local recurrences after the operation (cervical cancer and vaginal cancer). Colposcopy and biopsy were performed in 27 patients before enrolment, and CIN 3 or VAIN 3 or worse was diagnosed in 21 patients. Characteristics of the patients are shown in Table 1.
Table 1. Characteristics of patients.
Numbers, n
|
28
|
Age (mean, range), years
|
43 (25-68)
|
Preoperative diagnosis, n VAIN
CIN
|
2
26
|
Diagnosis of colposcopy guided biopsy, n
< VAIN 3 and < CIN 3
CIN 3
SCC
|
6
17
4
|
Intervention, n Cervical and resection of vagina
Mapping biopsy
|
24
4
|
Final diagnosis, n No dysplasia
CIN 2
VAIN 3 and CIN 3
SCC
|
4
1
19
4
|
VAIN: vaginal intraepithelial neoplasia, CIN: cervical intraepithelial neoplasia, SCC: squamous cell carcinoma.
Primary endpoint
Twenty-eight endoscopic images from the most prominent sites in the patients were analyzed. Table 2 shows the relationship between the ECS classification and grade of histological dysplasia. Sensitivity, specificity, PPV, NPV and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Endocytoscopy significantly increased the diagnostic performance compared to colposcopy-guided biopsy (P < 0.01).
Table 2. Correlations between ECS classification and histological diagnosis (the most prominent sites).
Biopsy
ECS classification
|
< CIN 3
< VAIN 3, n
|
≥ CIN 3
≥ VAIN 3, n
|
Total, n
|
ECS 1-3, n
|
7
|
1
|
8
|
ECS 4, 5, n
|
1
|
19
|
20
|
Total, n
|
8
|
20
|
28
|
CIN: cervical intraepithelial neoplasia, VAIN: vaginal intraepithelial neoplasia, ECS: endocytoscopy.
Sensitivity; 95.0 (84.8-98.6), specificity; 87.5 (61.9-96.5), PPV; 95.0 (84.8-98.6), NPV; 87.5; (61.9-96.5), accuracy; 92.9 (78.2-98.0) (95% CI).
Secondary endpoints
Excluding 2 images with poor staining, a total of 54 images including the most prominent site and surrounding area for each patient were evaluated (Table 3). Sensitivity, specificity, PPV, NPV and accuracy of endocytoscopic images were 92.0% (79.9-97.6%), 82.8% (72.4-87.5%), 82.1% (71.4-87.1%), 92.3% (80.7-97.6%) and 87.0% (75.9-92.2%), respectively. The ROC curve is shown in Figure 3 and the AUC was 0.89.
Table 3. Correlations between ECS classification and histological diagnosis (including the most prominent sites and surrounding area).
Biopsy
ECS classification
|
< CIN 3
< VAIN 3, n
|
≥ CIN 3
≥ VAIN 3, n
|
Total, n
|
ECS 1-3, n
|
4
|
2
|
26
|
ECS 4, 5, n
|
5
|
23
|
28
|
Total, n
|
29
|
25
|
54
|
CIN: cervical intraepithelial neoplasia, VAIN: vaginal intraepithelial neoplasia, ECS: endocytoscopy
Sensitivity; 92.0 (79.9-97.6), specificity; 82.8 (72.4-87.5), PPV; 82.1 (71.4-87.1), NPV; 92.3 (80.7-97.6), accuracy; 87.0 (75.9-92.2) (95% CI).
The relationship between colposcopy-guided biopsy and final histological diagnosis based on the operation is shown in Table 4. The accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%), which was similar to that in previous reports. On the other hand, the accuracy of ECA classification to final diagnosis was 85.7% (73.2-85.7%).
Table. 4 Correlations of histological diagnosis between colposcopy guided biopsy and final procedures.
Final procedure
Colposcopy
|
< CIN 3
< VAIN 3, n
|
≥ CIN 3
≥ VAIN 3, n
|
Total, n
|
< CIN 3
< VAIN 3 , n
|
2
|
5
|
7
|
≥ CIN 3
≥ VAIN 3, n
|
2
|
18
|
20
|
Total, n
|
4
|
23
|
27
|
CIN: cervical intraepithelial neoplasia, VAIN: vaginal intraepithelial neoplasia
Sensitivity; 78.3 (72.3-84.1), specificity; 50.0 (16.0-83.5) PPV; 90.0 (83.2-96.7), NPV; 28.6 (9.1-47.7), accuracy; 74.1(64-84.0) (95% CI).
The diagnostic performance of each observer is shown in Table 5. Inter-observer agreement among the three reviewers using Fleiss’ κ was 0.78 (0.08-9.88, P < 0.01), and indicating good agreement. There were no adverse events and endocytoscopy had no adverse effects on scheduled procedures and final diagnosis.
Table 5. Diagnostic performance of each observer.
Observer
|
Sensitivity
|
Specificity
|
PPV
|
NPV
|
Accuracy
|
A
(endoscopist)
|
88.0
(75.4-95.1)
|
82.8
(71.9-88.9)
|
81.5
(69.8-88.1)
|
88.9
(77.2-99.5)
|
85.2
(73.5-91.8)
|
B
(gynecologist)
|
92.0
(79.7-97.6)
|
79.3
(68.7-84.1)
|
79.3
(68.7-84.1)
|
92.0
(79.7-97.6)
|
85.2
(73.8-90.4)
|
C
(pathologist)
|
95.7
(83.1-99.2)
|
77.4
(68.1-80.1)
|
75.9
(65.9-78.7)
|
96.9
(84.4-99.3)
|
85.2
(74.5-88.2)
|
PPV: positive predictive value, NPV: negative predictive value.