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Li Y.,Womens Reproductive Health Laboratory of Zhejiang Province | Zeng W.-J.,Womens Reproductive Health Laboratory of Zhejiang Province | Ye F.,Womens Reproductive Health Laboratory of Zhejiang Province | Ye F.,Zhejiang University | And 5 more authors.
Gynecologic Oncology

Objective.: Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study. Methods.: A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using > 2 signals for hTERC together with ≥ 2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion. Results.: The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions. Conclusions.: hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions. © 2010 Elsevier Inc. All rights reserved. Source

Hu T.,Huazhong University of Science and Technology | Li S.,Huazhong University of Science and Technology | Chen Y.,Hunan Province Tumor Hospital | Shen J.,Central Hospital of Wuhan | And 26 more authors.
European Journal of Cancer

Objective: Neoadjuvant chemotherapy (NACT) for cervical cancer still remains controversial. NACT was evaluated to establish selection criteria. Methods: A matched-case comparison was designed for the NACT group (n = 707) and primary surgery treatment (PST; n = 707) group to investigate short-term responses and high/intermediate risk factors (HRFs/IRFs). The 5-year disease-free survival (DFS) and overall survival (OS) rates were stratified by NACT response, HRFs/IRFs, International Federation of Gynecology and Obstetrics (FIGO) stage and tumour size, respectively. Results: The clinical and pathological response rates were 79.3% and 14.9% in the NACT group. In comparison to the PST group, IRFs but not HRFs were significantly decreased (P < 0.05), and the 5-year DFS rate was significantly improved in the NACT group (88.4% versus 83.1%, P = 0.021). Moreover, the 5-year DFS and OS rates were favourably increased in the clinical responders in comparison to the PST group and the clinical non-responders (P < 0.05). Compared to those of clinical non-responders, the 5-year DFS and OS rates of clinical responders, with or without HRFs, were also significantly increased (P < 0.01). In stage IB2, the 5-year DFS and OS rates were significantly increased, whereas operation duration declined in the NACT group (P < 0.05). For patients with stage IB tumours of 2-5 cm, the 5-year DFS and OS rates of clinical responders were significantly improved (P < 0.05). Conclusions: NACT is a suitable option for patients with cervical cancer, especially for NACT responders and patients with stage IB, which provides a new concept of fertility preservation for young patients. © 2012 Elsevier Ltd. All rights reserved. Source

Hu T.,Huazhong University of Science and Technology | Wu L.,Central South University | Xing H.,Huazhong University of Science and Technology | Yang R.,Huazhong University of Science and Technology | And 17 more authors.
Annals of Surgical Oncology

Background: There is no consensus on the selection criteria for ovarian preservation in cervical cancer, and the role of neoadjuvant chemotherapy (NACT) on ovarian metastasis (OM) is also unknown. Methods: A total of 1,889 cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB to IIB who underwent radical hysterectomy, pelvic lymphadenectomy, and bilateral salpingo-oophorectomy with or without NACT were enrolled. Clinicopathologic variables were studied by univariate and multivariate analyses. Meta-analyses of published data for risk factors of OM were also performed. Results: Twenty-two (1.2 %) of 1,889 patients were diagnosed as OM: 12 squamous cell carcinomas (SCC, 0.7 %), five adenocarcinomas (2.7 %), four adenosquamous carcinomas (5.6 %), and one small cell carcinoma (7.7 %). Multivariate analysis revealed that lymph node metastasis (LNM; odds ratio 5.75, 95 % confidence interval 2.16-15.28), corpus uteri invasion (CUI; 5.53, 2.11-14.53), parametrial invasion (PMI; 8.24, 3.01-22.56), and histology and NACT (0.40, 0.13-1.22) were associated with OM. Furthermore, OM in patients with SCC was associated with PMI (5.67, 1.63-19.72), CUI (3.25, 0.88-12.01), and LNM (9.44, 2.43-36.65). FIGO stage (IIB vs. IB; 31.78, 1.41-716.33), bulky tumor size (12.71, 1.31-123.68), PMI (51.21, 4.10-639.19), NACT (0.003, 0.00-0.27), and CUI (44.49, 2.77-714.70) were independent clinicopathologic factors for OM in adenocarcinomas. In the meta-analysis, we identified six risk factors for OM: LNM, CUI, PMI, adenocarcinoma, large tumor size, and lymphovascular space involvement. Conclusions: Ovarian preservation surgery may be safe in SCC patients without suspicious LNM, PMI, and CUI, and in adenocarcinomas in patients who received NACT without FIGO stage IIB disease, bulky tumor size (>4 cm), suspicious PMI, and CUI. © 2012 Society of Surgical Oncology. Source

Li S.,Huazhong University of Science and Technology | Li X.,Huazhong University of Science and Technology | Zhang Y.,Huazhong University of Science and Technology | Zhou H.,Huazhong University of Science and Technology | And 38 more authors.

Background: Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Methods: Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). Results: In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Conclusions: Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy. Source

Li S.,Huazhong University of Science and Technology | Hu T.,Huazhong University of Science and Technology | Chen Y.,Central South University | Zhou H.,Huazhong University of Science and Technology | And 6 more authors.

Radiotherapy is the standard treatment for cervical cancer, but causes radiotherapy-induced complications. Recently, chemotherapy has been more extensively utilized. Here, we perform a large-scale comparison of chemotherapy and radiotherapy. From 2002 to 2008, 2,268 patients were grouped according to adjuvant radiotherapy or chemotherapy before and/or after surgery, and we compared the 5-year overall survival (OS) and disease-free survival (DFS) rates, recurrence rates, side effects, quality of life (QoL), and sexual activity. There were no significant differences between the treatment groups for the 5-year OS and DFS rates (OS: p = 0.053, DFS: p = 0.095), although marginally improved outcomes were observed in the chemotherapy group (OS: 86.5% vs. 82.8%; DFS: 84.5% vs. 81.4%). However, patients with early-stage disease, clinical response, and younger age had increased 5-year OS and DFS rates following chemotherapy compared to radiotherapy (p<0.05). The chemotherapy group exhibited significantly lower 5-year recurrence and distant failure rates compared to the radiotherapy group (p<0.001 and p = 0.007, respectively). Nausea and vomiting were the most frequent short-term complications of chemotherapy, whereas bowel and urinary complications were more frequent in the radiotherapy group. Compared to the chemotherapy group, patients who received radiotherapy reported a lower QoL, less frequent sexual activity, and more severe menopausal symptoms (p<0.05). Cervical cancer patients treated with chemotherapy, especially those with early-stage disease, clinical responses, and younger ages, have more positive outcomes, fewer complications, better QoL and sexual activity, suggesting that chemotherapy may be a valuable alternative option for selected patients. © 2013 Li et al. Source

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