Interpretation
In this study, the sensitivity and specificity of the
conventional
colposcopy were 54.2% and 60.8%, which was at a relatively low level
compared with previous research6, 7. Most of the
statistics in previous studies referred to the detection efficiency of
CIN 2+ by colposcopy11, 16, 17, and our study included
CIN 1 as a positive pathological result. The sensitivity of the
conventional colposcopy to detect
CIN 1 was only 16.7% (1/6) in our research. CIN 1 lesions were too mild
to show the staining reactions of acetic acid and iodine. When CIN 1 was
included in the statistics, the efficiency of colposcopy would generally
be reduced. In addition, the diagnostic efficiency may also be related
to the population we included. Previous studies had shown that HPV 16+
was related to clearer visual acetowhite changes in the epithelium,
therefore reaching a better diagnostic efficiency for
colposcopy18. Patients infected with any of the 16
high-risk types of HPV could be included in our study. The colposcopic
impression also varied between different observers19,
20. The application of dynamic spectral imaging colposcopy and related
intelligent algorithms would significantly improve the diagnostic
efficiency of colposcopy in the future21, 22.
The main outcome measure for
fluorescence colposcope was the
level of SBR at the lesions. We set a cut-off value and defined the
positive result as the SBR of the cervical sampling site was greater
than the cut-off value. For the conventional colposcope, the positive
results included the colposcope assessment impression of low grade, high
grade and cancer. The two types of colposcope displayed similar
efficiencies in identifying cervical precancerous lesions
on per-patient basis. However, the
fluorescence colposcope possessed
higher sensitivity and better NPV on
per-site basis. One of the major
advantages of the fluorescence colposcope was its high sensitivity, and
the minimum detectable concentration of the fluorescent dye was
approximately 2.7 μg/mL8. Because it was too
sensitive, some inflammatory lesions could also be recognized after
being stained with fluorescent dyes, which leads to the prevalence of
false positives. In addition, the cut-off value we set was different on
the per-patient basis and the per-site basis. At present, this
fluorescence colposcope is in the preliminary research stage, and the
exact SBR reference value cannot be determined yet. And more detailed
and standardized procedures also need continuous improvement.
In addition to the fluorescence signal at the lesions, we could
sometimes see the arc-shaped non-specific fluorescence signals at the
vaginal vault of the fluorescence colposcopy group, as shown by patient
No. 68 in Figure 2A. Before fluorescence colposcopy, unbound fluorescent
dyes need to be scrubbed off, and the vaginal vault area was prone to
residual fluorescent dyes and resulted in non-specific fluorescent
signals. Therefore, this fluorescence colposcope was not suitable for
detecting vaginal intraepithelial
neoplasia (VIN). Conventional colposcopy-guided biopsy with acetic acid
and Lugol’s iodine was crucial in detecting VIN23, 24.
In order to avoid missed diagnosis of VIN or vaginal cancer in this
study, suspicious vaginal lesions were also sampled for biopsy. However,
the SBRs of the vaginal lesions in the fluorescence colposcope group
could not be accurately calculated, so
the vaginal lesions in both groups
were not included in the statistical analysis.
A variety of fluorescent probes targeting tumors at the molecular and
cellular levels have been developed for image-guided
surgery25-27. However, there are few relevant studies
in colposcopy-guided biopsy. The fluorescence colposcope combined with
tumor-specific dye TMTP1-PEG4-ICG provides a new idea for the
identification of cervical cancer and precancerous lesions.