| Aims:To evaluate the feasibility and safety of conization with general electrosurgical knife in the management of cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma. Methods:A retrospective descriptive analysis was performed in a total of 1555 cases who underwent conization in Fudan University Shanghai Cancer Center between June 2004 and February 2010.The demographic data, comparison of histopathology by biopsy and conization, surgical complication were presented. The risk factors associated with disease recurrence were identified. Results:The mean age of all patients was 39.38 (18-72)years. The median volume of blood loss was 10ml, and the median duration of operation was 5 min. The histopathology of cone specimens and punch biopsies were consistent in 862 (78.36%) patients, while 81(7.36%) patients were confirmed to have more severe lesions in cone specimens.68 (6.18%) patients were diagnosed as invasive cervical cancer by conization. Positive surgical margins or endocervical curettage was found in 120 cases (10.39%). Among them,50 (4.33%) patients underwent subsequent surgery including secondary conization (3 cases), total abdominal hysterectomy (19 cases), radical hysterectomy(28 cases). Residual CIN2+ lesion were not found in 24 cases(48.00%) through the secondary surgery. Among 28 microinvasive carcinoma and 33 CIN2/3 patients, who had negative conization margins and had subsequent hysterectomy,52(85.25%) were clear of CIN2+ lesion in cervical specimens.916 patients (89.89%) were followed up from the end of conization till 2011/4/1. The median duration of follow-up was 33 months (14—81 months). Seventy-four (8.44%) case experienced surgical complications related to EKC including vaginal bleeding, pelvic infection, and cervical adhesion et al. Among them,14 (1.53%) patients underwent in-patient treatment. Twelve term pregnancies and one spontaneous miscarriage occurred during the follow-up. Thirty-nine (4.26%) cases were found persistence/recurrence during the follow-up with the mean interval of 9 months(1-36 months). Family history of malignancy, positive margins or endocervical curettage were the risk factors for persistence/recurrence by regression analysis.Conclusion:EKC was a simple, effective and safe diagnostic and therapeutic procedure for CIN and microinvasive carcinoma. purpose:THE aim of this study was to detect molecular alterations in exfoliated cells of cervical intraepithelial neoplasia and invasive cervical cancer, including HPV genotyping, amplification of the telomerase RNA gene (TERC), expression of P16 and methylation of (death-associated protein kinase) (DAPK), and identify their potential clinical implication in the diagnosis and prognosis of cervical lesions.Materials and Methods:1. Using the PCR-reverse blot hybridization, high risk HPV genotyping was performed in 162 cases of high grade cervical intraepithelial noplasia,92 cases of invasive squamous cervical cancers,36 cases of post-conization patients with possibly residual diseases and 50 cases of normal control. Copy numbers of the hTERC gene were measured by fluorescence in situ hybridization (FISH) using a dual-color probe containing the hTERC probe and the control, chromosome 3 centromere-specific probe (CSP3) in cervical liquid-based cytological (LBC) specimens from 53 squamous cell carcinomas (SCC),14 CINⅢ, and 20 normal controls.. P16 expression was detected by immunocytochemistry in cellblock samples from 52 cervical cancers, 136 CIN and 37 normal controls. The role of HPV genotyping, P16 expression and cytological morphology in the diagnosis of cervical lesions was compared. DAPK hypermethylation was examined by nested methylation specific PCR in cervical exfoliated cells from 54 ICC,52 CIN and 42 normal cervixes.Results:1. The prevalence of high risk HPV was 96.74% in SCC,90.74% in CIN and 26.00% in normal control respectively. The leading subtypes in SCC were HPV types 16,18,33,52,58, and 31; whereas HPV types 16,58,33,18,52 and 31 in CIN2/3. Multiple HPV infections were found in 23.79% of the patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HPV DNA test in detecting cervical cancer and intraepithelial neoplasia was 92.91%, 74%,94.78% and 67.27% respectively. Those values of HPV genotyping in the confirmation of residual lesions in patients with positive margins after conization was 77.27%,64.29%,77.27% and 64.29% respectively。2. Nucleus with abnormal FISH pattern for hTERC was observed in 0.94-90.65% of SCC cells and in 0-85.59% of CINⅢcells. Using the threshold of 5.89%, the occurrence of hTERC amplification in SCC and CINⅢwas similar (90.6% vs. 85.7%, P 130.630). However, the median percentage of cells with extra gains of hTERC (hTERC:CSP3> 1) in SCC was higher than in CINⅢ(64.3% vs.31.7%, P 13 0.001). Among those cells, the 3:2 signal pattern was the leading pattern for both SCC and CINⅢ; highlevel amplification of hTERC was more common in SCC than in CINⅢ(60.9% vs.48.9%, P 0.002). In SCC, it was not found that extra gains of hTERC were associated with any clinicopathological parameters.3. Diffuse overexpression of p16 was observed in both cytoplasms and nucleus of high-grade CIN cells and cancer cells, while not in normal cells. P16 expression was defined as grade 2, grade 1 and negative according to the intensity and the percentage of positive cells. Distribution of p16 expression (from grade 2 to negative) in invasive cancers was:78%,20% and 2% respectively, and 75.65%,21.74% and 2.61% in CINⅡ/Ⅲ, and 2.70%.16.22% and 81.08% in normal controls. Furthermore, HPV genotyping was more sensitive and p16 expression was more specific in the diagnosis of cervical lesions. P16 expression was observed in 77.78% (14/18) of cases with positive margins after conization, more common than in 33.33%(3/9) of cases without positive margin.4. DAPK hypermethylation was observed in 29 (53.70%) cervical cancers,29 (55.77%) CIN2/3 and 7 (16.67%) controls. The frequency of DAPK methylation was significantly higher in cervical cancer and intraepithelial neoplasia compared to the normal controls (both P value less than 0.001), while the frequency was similar between cancerous and precancerous lesions (P=0.848)Conclusions:.HPV genotyping, TERC amplification, p16 expression and DAPK methylation detected in cervical exofoliated cells could be useful in the detection of cervical cancer and precancers, among which, HPV genotyping was more sensitive and p16 expression was more specific. P16 overexpression might be valuable in the confirmation of residue disease in patients with positive margins after conization. TERC amplication pattern might have the potential role in the differential diagnosis of cervical cancerous and precancerous disease. DAPK hypermethylation woulb be an alternative marker on the detection of cervical lesions. However, the clinical implication of the above makers warrants further study in the follow-up of cervical lesions. |
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