[Characteristics of invisible cervical intraepithelial neoplasia Ⅲ under colposcopy]

Objective: To explore the human papilomavirus (HPV) genotypes and epithelial thickness of invisible cervical intraepithelial neoplasia Ⅲ (CIN Ⅲ) under colposcopy. Methods: One hundred and sixty-nine biopsies from 93 patients with a final diagnosis of CIN Ⅲ were extracted from the Shenzhen cervical cancer screening trial Ⅱ (SHENCCAST Ⅱ) . The SHENCCAST Ⅱ was conducted from 2009 to 2010. All the cervical blocks from these patients were re-cut and placed on 6 slides, i.e. sandwich model, with the top and bottom sections being stained with HE, the top second be processed for other studies, 3 sections for HPV genotypes by matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) assay. The thickness of squamous epithelium of CIN Ⅲ was measured by a microscope (×10) after re-cut. Colposcope directed CIN Ⅲ biopsies positively was defined as visible CIN Ⅲ, while random CIN Ⅲ biopsies positively was defined as invisible CIN Ⅲ. Results: HPV16 positivity was 37.2% (16/43) and 55.6% (70/126) between invisible and visible CIN Ⅲ biopsies, respectively (χ(2)=4.318, P=0.038) . Forty-nine cases of the 93 CIN Ⅲ patients were HPV16 positive, while 44 of them non-HPV16 positive. The proportion of patients with ≥45 years of age for other non-HPV16 positive 40.9% (18/44) was significantly higher than that HPV16 positive 20.4% (10/49; χ(2)=4.630, P=0.031) . Patients with HPV16 positive were more likely to have lesions ≥1 quadrant (χ(2)=7.786, P=0.005) than other non-HPV16 positive. Compared the average epithelium thickness of invisible CIN Ⅲ tissue (140±12) μm, the average epithelium thickness of visible CIN Ⅲ tissue (161±9) μm was thicker. There was statistical difference between two groups (t=4.383, P=0.038). The mean average epithelial thickness of CIN Ⅲ with HPV16 positive (172±11) μm was thicker than that the mean average epithelial thickness of CIN Ⅲ with non-HPV16 positive (130±10) μm (t=4.784, P=0.031) . Conclusions: Invisible lesions is difficult to identify under colposcopy and is related to non-HPV16 positive, small lesion size and thinner squamous epithelium. For non-HPV16 positive or older women should be performed colposcope directed biopsies and randomly multi-sites biopsies by colopscopy, which may be helpful to improve the detection of CIN Ⅲ and to reduce miss diagnosis.