摘要目的:探讨细胞学p16 INK4a免疫化学染色用于宫颈癌早期诊断的临床价值。 方法:募集2018年3—8月深圳周边地区902名25~60岁有性生活非妊娠期女性进行宫颈癌筛查，同时行宫颈新柏氏薄层液基细胞学（TCT）、高危型人乳头状瘤病毒（HPV）检测和细胞学p16 INK4a检测。任一检测结果阳性者均行阴道镜下宫颈四象限定点+随机活检+宫颈管搔刮方案，由2位细胞病理学主任医师对TCT和细胞学p16 INK4a进行判读阅片，评价p16 INK4a早期诊断宫颈上皮内瘤变（CIN）2+的效率和判读一致性。 结果:筛查人群中HPV、p16 INK4a和TCT≥低级别鳞状上皮内病变（LSIL）/不典型腺细胞（AGC）阳性率分别为8.1%（73/902）、6.8%（61/902）和4.7%（42/902），任一筛查结果阳性者共137例，阴道镜回叫率79.6%（109/137），组织病理诊断为5例CIN2、5例CIN3。HPV阳性、p16 INK4a阳性和TCT≥LSIL/AGC诊断CIN2+的灵敏度分别为100.0%、90.0%和80.0%，特异度分别为94.4%、95.3%和96.8%，差异均无统计学意义（均 P>0.05）。两位细胞病理学医师对p16 INK4a和TCT判读的Kappa值分别0.944和0.425。 结论:在宫颈癌筛查中，p16 INK4a检测具有与HPV、TCT检测相近的灵敏度和特异度，而且细胞病理学医师对p16 INK4a判读的主观差异小，提示p16 INK4a检测作为新的宫颈癌筛查方法具有一定优势。

abstractsObjective:To investigate the use of p16 INK4a immuno-stained cytology as the primary screening for cervical cancer prevention. Methods:From March to August 2018, 902 women from Shenzhen and surrounding area were recruited for cervical cancer screening with ThinPrep Cytologic Test (TCT), cobas4800 HPV test, and p16 INK4a co-test. Colpo/biopsies were performed using the point of interest biopsy protocol of directed and random cervical biopsies plus endocervical curettage for all women, any of whose tests was positive. Two senior cytopathologists interpreted TCT and p16 INK4a test. The performance of p16 INK4a for early detection of CIN2+ and inter-observer reproducibility of the interpretation of p16 INK4a were evaluated. Results:The positive rates of HPV test, p16 INK4a co-test and TCT diagnosed as LSIL/AGC or higher grade were 8.1% (73/902), 6.8% (61/902) and 4.7% (42/902), respectively. Colposcopy referring rate was 79.6% (109/137), among which 10 cases were diagnosed as CIN2+ (5 cases of CIN2 and 5 cases of CIN3). The sensitivity and specificity for CIN2+ of p16 INK4a test, TCT (LSIL/AGC or higher grade) and HPV test were 90.0%, 80.0%, 100.0% and 90.9%, 91.9%, 82.5%, respectively. Compared to TCT and HPV test, there was no significant difference in sensitivity and specificity between p16 INK4a and TCT/HPV test ( P>0.05). The Kappa value of the 2 cytopathologists in interpreting p16 INK4a and TCT was 0.944 and 0.425, respectively ( P<0.05). Conclusions:p16 INK4a for cervical cancer screening is equally sensitive to HPV test and specific to TCT while subjective difference of cytopathologists′ interpretation of p16 INK4a is small. Therefore, p16 INK4a can be used as a new cervical cancer screen method for its better diagnostic performance.