To explore the clinical efficacy of p16/minichromosome maintenance protein (MCM) 2 and p16/Ki-67 immunocytochemical double staining in screening cervical lesions in high-risk human papilloma virus (HR-HPV) positive women.

From April to October, 2015, a total of 62 women who were tested as HR-HPV positive in a cervical cancer screening program conducted in Shuangliu County, Chengdu, Sichuan Province and consistent with the inclusion and exclusion criteria of this study were selected as research subjects. The cervical exfoliative cytology specimens of these 62 HR-HPV positive women were collected and ThinPrep liquid-based cytology test (TCT) detection, p16/MCM2 and p16/Ki-67 immunocytochemical double staining were performed on the same specimen of each HR-HPV positive woman. Women infected with HPV-16/18, or other 12 types of HR-HPV (HPV-31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68) with cytological abnormalities in cervical exfoliated cells TCT detection (≥ atypical-squamous cells of undetermined signification, ≥ASCUS) were examined by colposcopy. And if the colposcopy result was abnormal, cervical biopsy was then conducted on the woman. The sensitivities, specificities and area under curve (AUC) of the operator characteristic (ROC) curves of p16/MCM2 and p16/Ki-67 double staining in HR-HPV positive women for the detection of cervical lesions were compared with those of cervical exfoliated cells TCT detection by statistical methods, in order to evaluate the efficiency of p16/MCM2 and p16/Ki-67 double staining. This study was approved by the Medical Ethics Committee of Sichuan University (No. K2014018). All women signed informed clinical research consents.

①Among the 62 HR-HPV positive women, the positive rates of p16/Ki-67 and p16/MCM2 were both significantly increased with the histological severity, and both the differences were statistically significant (χ²=21.947, P<0.001; χ²=5.268, P=0.022). While the positive rate of cervical exfoliated cells TCT detection had no obvious relationship with the histological severity, and the difference was not statistically significant (χ²=1.850, P=0.174). ②The positive rate of p16/Ki-67 in HPV-16/18 positive women was 69.2%(9/13), which was significantly higher than that in other 12 HR-HPV positive women 36.7%(18/49), and the difference was statistically significant (χ²=4.413, P=0.036), while there was no significant difference with regards to p16/MCM2 (χ²=2.510, P=0.113). ③Among the 62 HR-HPV positive women, the sensitivities of cervical exfoliated cells TCT detection, p16/MCM2 and p16/Ki-67 double staining and in HR-HPV positive women for the detection of cervical lesions were 47.1% (8/17), 94.1%(16/17), and 88.2% (15/17), respectively, and the specificities were 68.9% (31/45), 75.6% (34/45), and 42.2% (19/45), respectively. The ROC-AUC curve of p16/Ki-67 double staining in HR-HPV positive women for the detection of cervical lesions was 0.848, which was larger than that of cervical exfoliated cells TCT detection 0.580, and the difference was statistically significant (Z=2.736, P=0.006), while there was no significant difference between p16/MCM2 double staining and cervical exfoliated cells TCT detection (Z=0.651, P=0.515).

The sensitivity and specificity of p16/Ki-67 double staining are both higher than those of cervical exfoliated cells TCT detection in HR-HPV positive women for the detection of cervical lesions. And p6/Ki-67 double staining is simple to operate, its results are easy to interpret. It is highly prosperous to be used as an effective triage method for colposcopy referral in areas with serious shortage of medical resources and cytologist. However, the diagnostic value of p16/MCM2 double staining in HR-HPV positive women for the detection of cervical lesions needs further study to confirm.