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.