To Investigate The Optimal Practical Proposal For Diagnosis And Management Of Cervical Precancerous Lesions

Objective:To investigate the optimal practical proposal for diagnosis and management of cervical precancerous lesions from the clinical study and the combination with study of molecule biology markers. Methods:The practical value and significance of visual inspection with acetic acid and lugol’s iodine (VIA/VILI) in cervical cancer screening were assessed with example. The relationship of biomakers with CIN was studied. The methylation status of fragile histidine triad (FHIT) gene was detected by methylation-specific polymerase chain reaction (MS-PCR); the expression of FHIT protein and survivin protein was detected by immunohistochemical (IHC) method. Results:There were 116 cases of CINⅠgrade, 34 cases of CINⅡgrade,12cases of CINⅢgrade with 2 cases being cervical carcinoma in situ (CIS), and 2 cases of cervical cancer (CC) IA1 stage among 291 cases of colposcopy directed biopsy in 2006 screened women in 2008. The sensitivity and specificity of VIA and VILI were 98.78% and 100%;90.01% and 90.01% respectively. The positive predictive value and negative predictive value of VIA and VILI were 46.82% and 47.13%; 99.88% and 100% respectively. During the cervical cancer screening program in 2009, there were 2003 women attended. There were 199 cases who underwent colposcopy directed biopsy among whom 119 cases being CINⅠ,12 cases being CINⅡ,13 cases being CINⅢwith 2 cases being CIS. The sensitivity and specificity of VIA and VILI in 2009 were 99.31% and 100%,94.24% and 93.92% respectively. The positive predictive value and negative predictive value of VIA and VILI in 2009 were 57.20% and 56.03%,99.94% and 100% respectively. though the difference in the rates of colposcopy directed biopsy between 2008 and 2009 is not significant (P>0.05), the differences in the constituent ratio of benign changes and CIN lesions were significant (P<0.005), with the former was higher in 2008 than in 2009, the latter was lower in 2008 than in 2009. There were 1502 women who had attended the 2008 VIA/VILI screen took the follow year examination of VIA/VILI in 2009. The rates of CIN lesions were 81.76%o (164/2006) and 47.27‰(71/1502) respectively in originally screened group in 2008 and in follow-up examination of the same group, and the difference was highly significant (P＜0.005). For lesions of severe than CINⅡ, the difference of positive rates in the above groups was also highly significant with the follow-up examination group had a much lower incidence than the originally screened group (P＜0.005). The positive rates and staining strengths of survivin protein expression rising with the progress of CIN grade, with the positive rates of survivin protein expression in CINⅠ, CINⅡ, and CINⅢwere 74.07%,100%, and 100% respectively, and the staining strength was stronger in CINⅢthan in CINⅡ(P＜0.05). The rates of declined expression of FHIT protein rising with the progress of CIN grade, with the rates of declined FHIT protein expression in CINⅠ, CINⅡ, and CINⅢwere 29.63%(16/54),45.45%(10/22) and 53.33%(32/60) respectively. There was a rising trend in the rates of FHIT gene methylation status, with the methylation rates of FHIT gene in CINⅠ, CINⅡ, and CINⅢwere 37.04%(20/54),45.45%(10/22) and 48.33%(29/60) respectively. The positive rates and staining strength of survivin protein expression was related with specific HPV genotype infected in the CIN lesions. Of all CINⅡ/Ⅲmonotype HPV infected cases; the most common types were HPV-16, HPV-33, and HPV-58. The expression of survivin was strongest in HPV-16 infected cases, weakest in HPV-58 infected cases with modest in HPV-33 infected cases, and the differences were significant (P＜0.01). The expression of survivin was also related with the atypia of cervical cells. The staining strength of survivin was stronger in groups of high-grade squamous intraepithelial lesion (HSIL) than in groups of low-grade squamous intraepithelial lesion (LSIL), and it was stronger in LSIL group than in groups of atypical squamous cells of undetermined significance (ASCUS) and negative for intraepithelial lesion or malignancy (NILM) (P<0.001). The positive rate of survivin expression in CINⅠlesions which reversed afterward was 59.38%, while in CINⅠlesions which persisted or progressed afterward was 95.45%, the staining strength of the former was mean 0.59, standard deviation 0.50; and the later was mean 1.05, standard deviation 0.38, and the difference was statistically significant (P＜0.01). The declined expression of FHIT protein had no obvious relationship with the described above HPV genotype and morphological changes of cervical cells (P>0.05). The rate of declined expression of FHIT protein in CINⅠlesions which regressed afterward was 25%(8/32), and in CINⅠlesions that persisted or progressed afterward was 36.36%(8/22). The methylation rate of FHIT gene was higher in HPV-33 monotype infected CINⅡ/Ⅲlesions that was 83.33%(5/6) than in HPV-16 and HPV-58 monotype infected CINⅡ/Ⅲlesions, which were 46.15%(12/26) and 50%(3/6) respectively. There was no obvious relationship in the methylation status of FHIT gene with morphological changes of cervical cells (P>0.05). The methylation rate of FHIT gene in CINⅠlesions which revered afterward was 25%(8/32), and that in CINⅠlesions that persisted or progressed afterward was 4.55%(12/22); and the difference was statistically significant(P<0.05). Conclusions:The screen method of VIA and VILI have a good sensitivity and low probability. To control the excessive cervical biopsy just need to improve the skill of the diagnosis of colposcopy physician. So the screening method of VIA and VILI for cervical precancerous lesions and cervical cancer are the optimal practical methods for most people in our country. The positive rates and staining strengths of survivin protein expression rise with the progress of CIN grade. The rates of declined expression of FHIT protein rise with the progress of CIN grade. There is a rising trend of the FHIT gene methylation rates accompanying the progress of CIN grade. The positive expression of survivin protein, the declined expression of FHIT protein and the methylation of FHIT gene can be applied as references for the judgment of the severity of CIN lesions. The negative expression of survivin protein and the low methylation status are valuable biomakers for the prediction of the regression of CINⅠlesions, which might provide reference for the management of CINⅠ.