| Objective:To explore the value of p16INK4a and Ki67 immunocytochemistry and Genotyping of HPV by flow-through hybridization on cell specimens of LCT to screen cervical squamous carcinoma and preneoplastic lesions of the uterine cervix.Method:A total of 194 cytology specimens and 91 tissue samples were analyzed. lmmunocytochemistry and immunohistochemistry were used to detect the expression of p16INK4a and Ki67 on exfoliated cells and the corresponding biopsies;the genotypes of 48 specimen of cervical cytology were detected with HybriMax and all samples were compared with that of histological diagnosis simultaneously.The results were analyzed by SPSS11.5 using chi-square test,Spearman' rank correlation,Kendall's tau-b correlation and One-Way ANOVA.Results:①The positive rates of p16INK4a in the groups of NILM,ASC-US,ASC-H,LSIL,HSIL,SCC were 4.17%(1/24),35.14%(26/74),85.71%(6/7),80%(36/45),100%(41/41),100 %(3/3) respectively.The differences between each two groups of NILM,ASC(ASC-US+ASC-H),LSIL and HSIL(HSIL+SCC) were significant(p＜0.0083).There was obvious distinction between the group ASC—US and ASC—H(X2 =87.58,P=0.0000).The intensity of p16INK4a immunocytochemistry correlated well with the degree of cervical neoplasia(r=0.722,p＜0.01).The sensitivity,specificity,positive predictive value,negative predictive value of cervical exfoliated cells immunostaining for p16INK4a to detect high grade squamous intraepithelial lesion were100%,65.63%,83.58%,100%respectively.②HSIL,SCC and ASC-H groups showed high count of Ki67 and the differences between each two groups of NILM,ASC(ASC-US+ASC-H),LSIL and HSIL(HSIL+SCC) were marked.There was positive correlation between the expression of Ki67 and degree of cervical lesions(r=0.577,P＜0.001) so was the expression of Ki67 and p16INK4a(r=0.716,P＜0.01). The sensitivity,specificity,positive predictive value,negative predictive value of cervical exfoliated cells immunostaining for Ki67 to detect high grade squamous intraepithelial lesion were 92.86%,75.00%,86.67%,85.71%respectively.③The accordance of immunocytochemistry about Ki67/p16INK4a and histological diagnosis were 87.30%(55/63) and 80.95%(51/63) respectively on LSIL and higher grade lesions in 91 samples.④In 48 cases the total infection positive rate of HPV was 70.83%(34/48) and the HR-HPV positive rate was 54.17%(26/48).Single infection rate of various HPV genotypes was 29.17%(14/48) in our study;Co-infection by 2,3,4,5 genotypes accounted for18.75%(9/48),18.75%(9/48),2.10%(1/48),and 2.10%(1/48) respectively.Viral genotype 16 ranked first with 31.25%,then followed by 6 with 20.83%,58 with 18.75%,33 with 14.58%,18with12.5%,53 with12.5%,52 with 8.33%,CP8304 with 6.25%,68 with 4.17%,31with 2.08%,66 with 2.08%,11 with 2.08%,39with2.08%,43with 2.08%,59 with 2.08%.And genotypes of 45,56,44,51,42,35 were not detected.The HR-HPV positive rate in the groups of NILM, ASC,LSIL and HSIL were 33.33%,53.85%,60%,100%respectively.The distinction among these four groups was significant(X2=9.7803,P= 0.0205).In the cases defined as CIN(CINI～CINIII),a significantly higher incidence of person with multiple HPV infection94.12%(16/17) than that with single infection 35.29%(6/17)(P=0.0167).For detecting high grade cervical intraepithelialneoplasia, the sensitivity,specificity,positive predictive value,negative predictive value were 100%,52.63%,55%,100%respectively.Conclusion:①HPV infection,up-regulated expression of p16INK4a and the elevation of Ki67 LI are closely related to cervical cancer and precancerous lesions of cervix.②HR-HPV infection is one of the reasions for the up-regulation of p16INK4a.③There is an important significance of HPV genotyping for the diagnosis,therapy,follow-up and efficacy evaluation of cervical squamous carcinoma and preneoplastic lesions of the uterine cervix.④High expression of p16INK4a and the LI of Ki67 have positive correlation with the degree of cervical lesions.And they can provide clinicians with valuable assistant indexes for evaluating patient's condition,estimating progress and predicting prognosis.⑤The detection of the expression about p16INK4a and Ki67 and genotyping of HPV are important for evaluating high grade cervical lesions,reducing omission diagnostic rate and early diagnosis of cervical cancer.⑥The detection of the expression about p16INK4a and Ki67 and genotyping of HPV can be used for the further classification of the ASC-US patients.⑦Using residual LCT specimens for immunocytochemistry and HPV genotyping simultaneously can alleviate patient's agony and economic burden.Meanwhile it can provide reliable auxiliary index to clinicians.⑧HybriMax combines flow-through hybridization with gene chip.It is a rapid hybridization platform which is high sensitive and efficient. |
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