p16INK4a/Ki-67双免疫细胞化学染色对宫颈细胞学不能明确意义的不典型鳞状细胞和低级别鳞状上皮内瘤变患者的分流作用

Sorting role of p16INK4a/Ki-67 double immunostaining in the cervical cytology specimens of ASCUS and LSIL cases

目的 探讨p16INK4a/Ki-67双免疫细胞化学染色法对宫颈细胞学结果为不能明确意义的不典型鳞状细胞（ASCUS）和低级别鳞状上皮内瘤变（LSIL）患者的分流作用.方法 收集2014年4月至2015年2月宫颈液基细胞学结果为ASCUS（318例）或LSIL（102例）的420例患者资料,包括剩余细胞学样本、高危人乳头状瘤病毒（HPV）检测结果、活检结果和随访资料,采用p16INK4a/Ki-67双免疫细胞化学染色法检测细胞学样本.以活检结果为参照,比较p16INK4a/Ki-67双免疫细胞化学染色法和高危HPV检测法筛查宫颈癌前病变或宫颈癌[包括宫颈上皮内瘤变（CIN）2、CIN3、原位癌及浸润性癌,简称为CIN2＋]的灵敏度和特异度.结果 采用宫颈细胞学筛查CIN2＋时,p16INK4a/Ki-67双免疫细胞化学染色法与高危HPV检测相比,灵敏度略低（84.2%比94.7%）,特异度较高（84.0%比53.9%）.在ASCUS患者中,p16INK4a/Ki-67双免疫细胞化学染色法与高危HPV检测的灵敏度分别为82.6%和91.3%,特异度分别为88.8%和63.7%;在LSIL患者中,p16INK4a/Ki-67双免疫细胞化学染色法与高危HPV检测的灵敏度分别为86.7%和100.0%,特异度分别为67.8%和20.7%.在＆lt;30岁患者和≥30岁患者中,p16INK4a/Ki-67双免疫细胞化学染色法的特异度均较高（80.8%和84.5%）,而高危HPV检测的特异度明显较低,分别为42.3%和56.9%.结论 p16INK4a/Ki-67双免疫细胞化学染色对于筛查宫颈细胞学样本CIN2＋兼具较高的灵敏度和特异度,其特异度高于高危HPV检测,能有效分流细胞学ASCUS或LSIL中的高危人群.对于年龄〈30岁的女性患者,p16INK4a/Ki-67双免疫细胞化学染色法可能是一个潜在的细胞学联合筛查或初筛工具.

Objective To investigate the sorting effect of p16INK4a/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance （ASCUS） or low-grade squamous intraepithelial lesion （LSIL） cytology results. Methods Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS （n=318） and LSIL （n=102） were selected, and residual liquid-based cytology specimens were used for p16INK4a/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV. Taking histological follow-up as the gold standard, the test was considered positive when at least one cell exhibited p16INK4a/Ki-67 co-staining, without requirement of adjunct morphologic interpretation of positive cells. Results Further screening CIN2＋ in cytology ASCUS and LSIL group , the sensitivity of p16INK4a/Ki-67 double immunostaining was slightly lower than high risk HPV （84.2% vs. 94.7%）, while the specificity was higher （84.0% vs. 53.9%）. For ASCUS patients, the sensitivity of p16INK4a/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. For LSIL patients, the sensitivity of p16INK4a/Ki-67 double immunostaining and high risk HPV was 86.7% and 100.0%, and the specificity was 67.8% and 20.7%, respectively. For patients younger and older than 30 years, specificity of p16INK4a/Ki-67 double immunostaining was both higher than that of high risk HPV （80.8% vs. 42.3%;84.6% vs. 56.9%）. Conclusions p16INK4a/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. p16INK4a/Ki-67 double immunostaining may benefit patients younger than 30 years of age as a preliminary or potential cytology-combining screening tool..