Introduction
Cervical cancer is the third most common female cancer worldwide. With
the improvement of screening methods and the application of human
papillomavirus (HPV) vaccines, the cervical cancer elimination plan in
developed countries is accelerating1. More than 85%
of cervical cancer deaths currently occur in low- and middle-income
countries. Because of large population, significant regional
socioeconomic disparities, and insufficient medical resources, cervical
cancer continues to be a serious public health problem in the developing
world, including China2. Improving screening methods
for cervical cancer is crucial. Guidelines recommend that
women aged 21-29 years
should perform cervical cytology
test every three years and women aged 30-65 years should co-test with
cytology and HPV every 5 years3. When these cervical
cancer screening results are abnormal, colposcopy
and colposcopy-directed biopsies
are then recommended.
Colposcopy plays a pivotal role in reducing the incidence and mortality
of cervical cancer. Colposcopy can provide real-time observation and
evaluation of the cervix to detect cervical intraepithelial neoplasia
(CIN)/squamous intraepithelial lesion (SIL) and invasive cancer. 3% to
5% acetic acid and Lugol’s iodine
solution are usually applied to identify potential lesions. The
colposcopists give colposcopic
colposcopy assessment impressions
according to visual changes, such as response to acetic acid
(acetowhitening), characteristics
of lesion borders, sizes and contours, vascular patterns, and degree of
iodine uptake4. Cervicitis is common in colposcopy,
and infected cervical cells may also become acetowhite after application
of acetic acid, resulting in false positive results5.
Professional training and visual acuity are necessary for the screening
providers. Because of the subjective nature and inherent inaccuracy of
the colposcopic impression, its diagnostic efficiency varies greatly and
is limited. Acetic acid and
Lugol’s iodine co-testing showed a sensitivity ranging 64-100% and a
specificity ranging 62-97% in detecting CIN
2+ dysplasia6,
7. Therefore, the development of indicators with higher diagnostic
efficiency has bright application prospects.
Previously, we developed a dual modal fluorescence colposcope for
simultaneous visible reflectance imaging and fluorescence imaging. The
fluorescence colposcope combined with tumor-targeting near-infrared
(NIR) fluorescent dye TMTP1-PEG4-ICG could help to evaluate cervical
lesions in real time8. TMTP1-PEG4-ICG possesses
advantages of increased tissue penetration and high sensitivity, can
specifically bind to cervical cancer or intraepithelial neoplasia cells,
making it an ideal molecular diagnostic agent9. The
preliminary clinical study including 11 involvers showed that the
fluorescent colposcope combined with TMTP1-PEG4-ICG could display
positive fluorescent signal at the lesions for squamous cell carcinoma,
adenocarcinoma and CIN8.
In order to evaluate the diagnostic efficiency of this
fluorescence colposcope combined
with the tumor-targeting dye
TMTP1-PEG4-ICG, we designed this
randomized controlled trial (RCT). Patients with abnormal cervical
cancer screening results were randomized to fluorescence colposcope
group and conventional colposcope
group, then the diagnostic efficiency of the two groups were compared.