Song Fangbin, Du Hui, Xiao Aimin, Wang Chun, Huang Xia, Yan Peisha, Liu Zhihong, Qu Xinfeng, Belinson Jerome L, Wu Ruifang
Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China.
Shenzhen Key Laboratory on Technology for Early Diagnosis of Major Gynecological Diseases, Shenzhen, People's Republic of China.
Cancer Manag Res. 2020 Sep 25;12:9067-9075. doi: 10.2147/CMAR.S273079. eCollection 2020.
When used for cervical cancer primary screening, liquid-based cytology (LBC) has a high specificity but a low sensitivity. For histological diagnosis of high-grade lesions, p16 immunostaining has proven to be useful. Therefore, our objective was to evaluate the use of p16 immuno-cytology as a primary screen and a secondary screen after primary high-risk human papillomavirus (hrHPV) screening or LBC screening.
A total of 1197 cytology slides were immuno-stained using automatic p16 staining system (PathCINp16) in two studies from cervical screening programs. In the primary screening study, 875 slides were randomly selected and analyzed for p16. In the secondary screening study, 322 of the remaining slides were chosen by virtue of being HPV 16/18+, other hrHPV+/LBC≥ASC-US, or HPV-negative/LBC ≥LSIL. The sensitivity and specificity for detection of cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+) were compared based on p16, LBC and HPV test results.
In combining two studies, there were 431 cases with biopsy pathology. They included 83 cases with CIN2+ and 41 cases with CIN3+. The p16 positivity rate increased with pathologic and cytologic severity (P<0.0001). For primary screening: p16 immuno-cytology was more specific than HPV testing and was similar in sensitivity. Also, p16 immuno-cytology compared favorably with routine LBC (≥ASC-US or ≥LSIL) in sensitivity and specificity. For secondary screening: after LBC screening, "Triaging ASC-US with p16" gave a higher specificity and a similar sensitivity as compared to the "Triaging ASC-US with hrHPV" algorithm. After HPV primary screening, p16 immuno-cytology was more specific than LBC (≥ASC-US); the calculated colposcopy referral rate was also decreased by using p16 immuno-cytology as triage. Triage of "HPV16/18 and p16" had higher specificity and similar sensitivity as compared to triage of "HPV16/18 and LBC ≥ASC-US".
For primary screening, p16 immuno-cytology compares favorably to routine LBC and HPV testing. p16 immunostaining could be an efficient triage to reduce the colposcopy referral rate after primary hrHPV screening or LBC screening. Therefore, p16 immuno-cytology may be applicable as a favorable technology for cervical cancer screening.
用于宫颈癌初筛时，液基细胞学检查（LBC）具有高特异性但低敏感性。对于高级别病变的组织学诊断，p16免疫染色已被证明是有用的。因此，我们的目的是评估p16免疫细胞学作为初筛以及在初次高危型人乳头瘤病毒（hrHPV）筛查或LBC筛查后的二次筛查的应用情况。
在两项宫颈癌筛查项目研究中，使用自动p16染色系统（PathCINp16）对总共1197张细胞学玻片进行免疫染色。在初筛研究中，随机选择875张玻片并分析p16情况。在二次筛查研究中，根据HPV 16/18阳性、其他hrHPV阳性/LBC≥非典型鳞状细胞不能明确意义（ASC-US）或HPV阴性/LBC≥低度鳞状上皮内病变（LSIL），从剩余玻片中选择322张。基于p16、LBC和HPV检测结果，比较检测宫颈上皮内瘤变2/3级或更严重病变（CIN2+/CIN3+）的敏感性和特异性。
两项研究合并后，有431例进行了活检病理检查。其中包括83例CIN2+病例和41例CIN3+病例。p16阳性率随病理和细胞学严重程度增加而升高（P<0.0001）。对于初筛：p16免疫细胞学比HPV检测更具特异性，敏感性相似。此外，p16免疫细胞学在敏感性和特异性方面与常规LBC（≥ASC-US或≥LSIL）相比具有优势。对于二次筛查：LBC筛查后，“用p16对ASC-US进行分流”与“用hrHPV对ASC-US进行分流”算法相比，具有更高的特异性和相似的敏感性。HPV初筛后，p16免疫细胞学比LBC（≥ASC-US）更具特异性；使用p16免疫细胞学进行分流计算得出的阴道镜转诊率也降低了。“HPV16/18和p16”分流与“HPV16/18和LBC≥ASC-US”分流相比，具有更高的特异性和相似的敏感性。
对于初筛，p16免疫细胞学与常规LBC和HPV检测相比具有优势。p16免疫染色可以作为一种有效的分流方法，以降低初次hrHPV筛查或LBC筛查后的阴道镜转诊率。因此，p16免疫细胞学可能是一种适用于宫颈癌筛查的良好技术。
