The Expression And Shunt Value Of P16 Protein In Women With ASCUS Or LSIL

ObjectiveCervical cancer is one of most common gynecological malignant tumor.Around the world,especially in the developing or less developed countries,cervical cancer has high morbidity and mortality.The main cause of the disease is the persistent infection of high-risk type of human papilloma virus.Some high-grade squamous intraepithelial lesion(HSIL)will progress to cancer,and low-grade squamous intraepithelial lesion often round into normal except a few patients will evolve.At present,there is still no useful biological marker to predict who will progress to cancer in the crowd with LSIL or ASCUS cytology.In this study,we will evaluate the expression and significance of P16 protein in these people who was ASCUS and LSIL cytology.To investigate the expression of p16 protein is for exploring it’s function in predicting high-grade squamous epithelial lesions(CIN2).MethodsWe collected 5485 patients who received colposcopy in Qilu Hospital of Shandong University because of high-risk type HPV infection or unusual cytology during January 2017 to October 2017.There are 3,332 women were biopsied due to abnormal cytology or abnormal acetic acidor and iodine test or which showed ulcerative masses or was suspected infiltrating carcinoma.Histopathological examination was performed by a pathologist.2397 specimens tested P16 protein.727 women were eliminate because the data were incomplete.The other 169 women were eliminate because with a history of hysterectomy and cervical lesions.The remaining 1501 women were included in the study.There are 421 women with ASCUS cytology and 268 women with LSIL cytology.The gold standard is the histopathology.According to different clinical treatment methods,these women were divided into two groups,one group is the histopathology ≤CIN1 and the other group is the histopathology ≥ CIN2.The p16 protein test is either positive or negative.HPV is classified as high risk positive and negative.According to different ages,they were divided into four groups:younger than 25 years old,26 to 45 years old,46 to 60 years old and older than 60 years old.Statistical software SPSS 20.0 was used for statistical analysis these datas.The rate or percentage(%)was used for statistical description.The sensitivity(SE),specificity(SP),positive predictive value(PPV),negative predictive value(NPV),positive likelihood ratio(+LR),negative likelihood ratio(-LR)and 95%CI of HR-HPV and P16 protein test for ≥CIN2 detection in the total screened population were calculated respectively.Chi-squared Test was used for comparison between different groups.Kruskal-wallis was used to examine the differences between age groups.P<0.05 was statistically significant.Results1.There are 28.05%(421/1501)women with ASCUS cytology,17.85%(268/1501)women with LSIL cytology.The high proportion of these two cases is related to the subjective influence of cytological diagnosticians from different regions and hospitals.2.According to the pathological classification,there were 147 cases in the group of NILM,among which 22 cases were P16 positive(15.00%)in the patients with ASCUS cytology.There were 109 cases in the group of CIN1,among which 47(43.12%)were P16 positive.There were 128 patients in the group of CIN2,among which 127 patients(99.22%)were P16 positive.There were 34 patients in CIN3 group,all patients(100.0%)with P16 positive.There were 3 cases in the group of cancer,all the 3 cases were P16 positive(100%).HR-HPV in the ASCUS cytology was determined.There are 124(84.35%)cases of HR-HPV were positive in NILM group,96 cases(88.07%)of HR-HPV were positive in CIN1 group;124(96.87%)cases of HR-HPV were positive in CIN2 group;34 cases(100.0%)of HR-HPV were positive in CIN3 group,three cases(100.0%)were hr-HPV positive in the cancer group.The positive rates of P16 and HR-HPV in ASCUS cytology increased with the rise of histological classification.3.Among the LSIL cytology patients,there were 63 cases in the group of NILM,among which 11 cases were P16 positive(17.46%).There were 76 cases in the group of CIN1,among which 39(51.32%)were P16 positive.There were 104 patients in the group of CIN2,among which 101 patients(97.12%)were P16 positive.There were 24 patients in CIN3 group,all patients(100.0%)with P16 positive.There were lcase in the group of cancer with P16 positive(100%).HR-HPV in the LSIL cytology was determined.There are 55(87.3%)cases of HR-HPV were positive in NILM group,72 cases(94.74%)of HR-HPV were positive in CIN1 group;101 cases(97.12%)cases of HR-HPV were positive in CIN2 group;24 cases(100.0%)of HR-HPV were positive in CIN3 group,One case(100.0%)were HR-HPV positive in the cancer group.The positive rates of P16 and HR-HPV in LSIL cytology increased with the rise of histological classification.4.In all abnormal cytology there are 49.36%(421/853)were ASCUS cytology,and the histological examination results showed that there are 39.19%(165/421)patients with ≥CIN2 lesion.The sample age ranged from 15 to 74.The average age is 41 years and the median age is 40 years.The difference between different age groups was statistically significant,and it was thought that the influence of age on ≥CIN2 lesions in patients with ASCUS cytology was different.5.In all abnormal cytology there are 31.42%(268/853)were LSIL cytology,and the histological examination results showed that there are 48.13%(129/268)patients with≥CIN2 lesion.The sample age ranged from 23 to 67.The average age is 40 years and the median age is 40 years also.Comparison between age groups X2=4.212,P=0.239(P>0.05),there was no statistically significant difference between age groups.It can be concluded that different ages have the same effect on>CIN2 lesions in patients with LSIL cytology.6.P16 protein was detected in patients with ASCUS and LSIL cytology.The sensitivity(SE)of P16 protein were 99.39%and 97.67%,and specificity(SP)were 73.04%and 64.03%,the positive predictive value(PPV)were 70.39%and 71.59%,and the negative predictive value(NPV)were 99.47%and 96.74%.The sensitivity(SE)of HR-HPV were 97.58%and 97.67%,and specificity(SP)were 14.06%and 8.63%,the positive predictive values(PPV)were 42.26%and 49.80%,and the negative predictive values(NPV)were 90.00%and 80.00%.The detection of P16 protein and HR-HPV have high sensitive in ASCUS and LSIL patients,but the specificity of HR-HPV was lower.The difference in sensitivity between P16 protein detection and HR-HPV have no statistically significant(P>0.05),the difference between specificities have statistically significant(P<0.05).7.The negative likelihood ratio(-LR)of P16 protein detection in ≥ CIN2 lesions were 0.008 and 0.036 in ASCUS and LSIL patients.The negative likelihood ratio(-LR)of HR-HPV were 0.17 and 0.27.There is less possibility sufferring from≥CIN2 lesions when the p16 protien test was negative.In summary,the sensitivity of P16 protein detection and HR-HPV in the diagnosis of>CIN2 lesions was high,but the specificity of P16 protein detection was much higher than HR-HPV,and the difference between the two was statistically significant(P<0.05).The-LR of P16 in both groups of ASCUS and LSIL cytology all less than 0.1.It indicated that the possibility of patients developing≥CIN2 lesions is very small when P16 is negative.These patients can be followed up for observation.Conclusion1.The p16 protein test is useful in identifing women who have higher risk for CIN 2 in patients with ASCUS or LSIL cytology;2.The P16 protein test could be used as a shunt mean of ASCUS and LSIL cytology;3.When the P16 protein test was negative,the patients who were ASCUS or LSIL cytology can be followed up for observation.