Yoshida Tomomi, Sano Takaaki, Kanuma Tatsuya, Inoue Hiroshi, Itoh Teruko, Yazaki Chiaki, Obara Mitsuo, Fukuda Toshio
Department of Laboratory Sciences, Gunma University, Maebashi, Japan.
Acta Cytol. 2011;55(5):413-20. doi: 10.1159/000331047. Epub 2011 Oct 8.
This study evaluated the usefulness of p16(INK4a)/Ki-67 as a new biomarker in the diagnosis of human papillomavirus (HPV)-related cervical lesions.
From 69 women with previous positive cytology, clinician-collected (CC) samples were obtained using a Cervex-Brush®. One month later, self-collected (SC) material was acquired using a Rovers® Viba-Brush. Liquid-based cytology specimens were prepared from both samples, and then the grades of squamous intraepithelial lesions (SIL) were determined; following immunostaining with CINtec® PLUS, HPV status was analyzed using a linear array.
The mean double-positive cell scores (SCORE) in the CC samples were 3.2 in samples negative for intraepithelial lesions or malignancy, 1.3 in atypical squamous cells of undetermined significance, 87.1 in low-grade SIL, and 367 in high-grade SIL. According to HPV risk type, the mean SCORE was 16 in samples negative for HPV, 8.4 in low-risk HPV, 143 in high-risk HPV other than type 16, and 420 in HPV16 - with a statistical significance between high-risk HPV and type 16 (p < 0.05). The SCORE of the SC group was lower than that of the CC group because of the limited number of cells collected.
The SCORE showed a significant correlation with HPV16 compared with lesser-degree lesions. CINtec PLUS is useful as a diagnostic marker of progression of lesions and a surrogate marker of an elevated risk of high-grade lesions with HPV16.
本研究评估p16（INK4a）/Ki-67作为一种新的生物标志物在诊断人乳头瘤病毒（HPV）相关宫颈病变中的作用。
从69例既往细胞学检查呈阳性的女性中，使用Cervex-Brush®获取临床医生采集（CC）的样本。1个月后，使用Rovers® Viba-Brush获取自我采集（SC）的样本。从这两种样本中制备液基细胞学标本，然后确定鳞状上皮内病变（SIL）的分级；在用CINtec® PLUS进行免疫染色后，使用线性阵列分析HPV状态。
CC样本中双阳性细胞的平均评分（SCORE）在无上皮内病变或恶性肿瘤的样本中为3.2，在意义不明确的非典型鳞状细胞中为1.3，在低级别SIL中为87.1，在高级别SIL中为367。根据HPV风险类型，HPV阴性样本的平均SCORE为16，低风险HPV样本为8.4，16型以外的高风险HPV样本为143，HPV16样本为420 - 高风险HPV与16型之间具有统计学意义（p < 0.05）。由于采集的细胞数量有限，SC组的SCORE低于CC组。
与程度较轻的病变相比，SCORE与HPV16显示出显著相关性。CINtec PLUS可作为病变进展的诊断标志物以及HPV16相关高级别病变风险升高的替代标志物。
