摘要目的 探讨阴道镜下隐匿子宫颈上皮内瘤变Ⅲ级(CINⅢ)病变的HPV亚型感染特征及鳞状上皮厚度.方法 对2009—2010年期间进行的深圳子宫颈癌筛查项目Ⅱ(SHENCCASTⅡ)研究中有完整资料、病理诊断为CINⅢ的93例患者的169个象限的CINⅢ组织的石蜡标本采用"三明治"法重新制作6张连续切片,其中第1张和最后1张行HE染色以明确病理诊断并确保其间的切片中含有同样级别的病变,第3~5张(第2张用于其他研究)共3张白片用于行基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)法HPV分型检测,并在显微镜下(×10)对CINⅢ病变部位的鳞状上皮厚度进行测量.其中,由阴道镜指示对可见病灶进行活检发现的CINⅢ定为"可见CINⅢ",通过子宫颈随机多点活检发现的CINⅢ定为"隐匿CINⅢ".结果(1)169个象限中,43个象限为隐匿CINⅢ、126个象限为可见CINⅢ,其HPV16型阳性率分别为37.2%(16/43)和55.6%(70/126),两者比较,差异有统计学意义(χ2=4.318,P=0.038).93例CINⅢ患者中,HPV16型阳性和非HPV16型阳性患者分别为49和44例,其中年龄≥45岁患者所占比例分别为20.4%(10/49)和40.9%(18/44),两者比较,差异有统计学意义(χ2=4.630,P=0.031);CINⅢ病灶>1个象限患者所占比例分别为79.6%(39/49)和52.3%(23/44),两者比较,差异也有统计学意义(χ2=7.786,P=0.005).(2)阴道镜下可见CINⅢ病变的鳞状上皮厚度为(161±9)μm,较隐匿CINⅢ病变者[(140±12)μm]厚,两者比较,差异有统计学意义(t=4.383,P=0.038).HPV16型阳性与非HPV16型阳性患者的CINⅢ病变的鳞状上皮厚度分别为(172±11)和(130±10)μm,两者比较,差异有统计学意义(t=4.784,P=0.031).结论 阴道镜下隐匿CINⅢ不易识别,可能与非HPV16型阳性、病灶范围小、病灶的鳞状上皮较薄有关.对非HPV16型阳性及年龄偏大者行阴道镜检查时,通过在子宫颈转化区域行病灶活检及多点随机活检,可提高CINⅢ的检出率,减少漏诊率.

abstractsObjective 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 Ⅲwere extracted from the Shenzhen cervical cancer screening trialⅡ(SHENCCASTⅡ).The SHENCCASTⅡwas 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 CINⅢwas 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(χ2=4.318,P=0.038).Forty-nine cases of the 93 CINⅢpatients 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; χ2=4.630, P=0.031).Patients with HPV16 positive were more likely to have lesions ≥1 quadrant(χ2=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 Ⅲtissue(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 Ⅲwith 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 CINⅢand to reduce miss diagnosis.