Concurrent chemoradiotherapy for cervical cancer： background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups

Concurrent chemoradiotherapy （CCRT） is regarded as the standard treatment for locally advanced uterine cervical cancer （LACC）, including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics （FIGO） staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage Ⅲ-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin （CDDP）, surgery following CCRT, adjuvant chemotherapy （CT） following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease.

Efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on advanced cervical cancer

Background and Objective: Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and standard therapy in recent years. Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50%. This study aimed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma. Methods: A total of 156 patients with stage IIa-IIIb cervical squamous cell carcinoma were randomly divided into the concurrent chemoradiotherapy group (experimental group) and radiotherapy group (control group). Intracavity and external beam radiation therapy were administered. At point A, 40-48 Gy were given by 10-12 fractions; at point B, 46-50 Gy were given by 23-25 fractions. In the same time, experimental group was treated by cisplatin (DDP, 40 mg) on day 1, repeated every week. Ten days after radiation therapy, TP regimen was administered as adjuvant chemotherapy. Results: For the experimental and control groups, the objective response rates were 88.61% and 75.32%, 1-year survival rates were 88.57% and 70.77%, 1-year local control rates were 81.43% and 64.62%, 3-year survival rates were 82.14% and 57.69%, and 3-year local control rates were 75.00% and 46.15%, with significant differences (P < 0.05). Quality of life of all patients were significantly improved after treatment (P< 0.05). Conclusion: Concurrent chemoradiotherapy plus adjuvant chemotherapy for advanced cervical cancer can improve short-term and long-term survival and local control rates of patients, improve the quality of life, and the toxicity can be tolerated.

Prognostic Impact of Carcinoembryonic Angtigen (CEA) in Locally Advanced Cervical Cancer Treated with Concurrent Chemoradiotherapy

Objective: To identify prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT). Methods and Materials: We analyzed 76 patients with FIGO stage IB2 - IVb cervical cancer treated with CCRT between 2001 and 2006 at the Nagoya University Hospital. Patients with an advanced cervical cancer treated with CCRT. Overall survival (OS) and Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. The log-rank test was used to test differences in survival. Fisher's exact test was employed for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. Results: The median age was 52, and the median follow-up period was 36 months. The 5 - year OS and PFS rates of all patients were 88.2% and 72.4%, respectively. Twenty-one of the 76 patients were diagnosed with recurrence. A higher serum CEA before CCRT was an independent predictive factor for a poor prognosis on multivariate analysis. Conclusions: A high level of serum CEA was a predictive factor for a poor prognosis. New strategies should be considered to control disease in this group of patients.

A randomized controlled trial of two chemotherapy regimens-paclitaxel liposome combined with platinum and paclitaxel combined with platinum in concurrent chemoradiotherapy for cervical carcinoma

Objective:The aim of the study was to compare the efficacy,side effect and influence on the survival rate of two chemotherapy regimens,paclitaxel liposome combined with platinum and paclitaxel combined with platinum,in concurrent chemoradiotherapy for cervical carcinoma.Methods:The 162 cases with primary cervical carcinoma diagnosed between January 2008 and November 2009 in Jiangxi Maternal and Child Health Hospital(China) were enrolled in this randomized controlled trial.Seventy-one cases were included in paclitaxel group and 91 in paclitaxel liposome group.And the chemotherapy doses were as follows:paclitaxel liposome and paclitaxel 135 mg/m2;cisplatin 80 mg/m2 or carboplatin AUC 4-6;then repeated every 21 days for two or three times.Radical radiotherapy was given to both groups at the same time.Efficacy was evaluated according to the tumor regression six months later and follow-up was done consistently.Results:The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89 % respectively(P > 0.05).The one year cumulative survival was 91.4% for paclitaxel group and 89.2% for paclitaxel liposome group(P > 0.05).The incidence rates of adverse effects such as rash,gastrointestinal toxicity,bone marrow suppression and muscle/joint pain in paclitaxel liposome group were much lower than those in paclitaxel group(P < 0.05),while there was no difference regarding hair loss,hepatic function damage,peripheral neuritis and other aspects(P > 0.05).Conclusion:Paclitaxel liposome plus platinum is a safe and effective method for staging IIa-IV cervical carcinomas.While the long-term efficacy should be further observed.

Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell growth.However,the expression,clinical significance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain unclear.Methods:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent tissues.The expression of circRNA_001896 was detected in 72 CC patients usingfluorescence quantitative PCR.Correlation analysis with clinical pathological features was performed through COX multivariate and univariate analysis.The effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis assays.Results:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC tissues.Fluorescence quantitative PCR confirmed circRNA_001896 as a circular RNA.High expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC patients.Proportional hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’prognosis.Cellular functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming ability.In vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC cells.Conclusion:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and survival period in patients.Moreover,downregulating circRNA_001896 significantly inhibits both in vivo and in vitro propagation of CC cells.Therefore,circRNA_001896 might be used as a biomarker for targeted therapy in cervical cancer.

Sarcopenia and Anemia Are Predictors of Poor Prognostic in Cervical Cancer Patients

Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study. Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia;51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin:the impact of chemoradiotherapy

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge.We report here our experience in treating these patients with chemoradiotherapy as a curative approach.Data from 40 patients were reviewed.In total,20(50%) patients underwent excisional biopsy.All patients underwent radiotherapy,which was delivered to both sides of the neck and pharyngeal mucosa(extensive field),and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2.The clinical stage of the cervical nodes at presentation was N1 in 25%,N2 in 60%,and N3 in 15%.Most patients(75%) developed at least grade 3 mucositis.Eight patients(20%) had grade 3 xerostomia and 18 patients(45%) required esophageal dilation for stricture.The 5-year overall survival(OS) rate of all patients was 67.5%.The 5-year OS rates of patients with N1,N2,and N3 lesions were 100%,67%,and 41%,respectively(P = 0.046).The 5-year progression-free survival rate was 62.5%.In multivariate analysis,only N stage significantly affected OS(P = 0.022).Emergence of the occult primary was very limited(1 patient only).Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor.Because the survival of patients with unknown primary is comparable to that of patients with known primary,an attempt at cure should always be made.

Impact of Survival Rate and Safety Analysis of Concurrent Chemoradiotherapy in Patients with Recurrent Cervical Cancer

Objective:To investigate the effect of concurrent chemoradiotherapy on the survival rate and safety of patients with recurrent cervical cancer.Methods:A total of 107 patients with recurrent cervical cancer who were treated in our hospital from March 2016 to January 2019 were retrospectively analyzed and randomly divided into the control group(n=53)and the observation group(n=54)and treated conventionally.On this basis,the control group was treated with radiotherapy,and the observation group was treated with concurrent radiotherapy and chemotherapy.The clinical efficacy,cellular immune index,survival rate and rate of adverse reactions were compared between the two groups.Results:Compared with the total effective rate of 79.25%in the control group,the observation group was 94.44%,and the difference was statistically significant(P<0.05).After treatment,the levels of NK,CD3+,and CD4+in the two groups were higher than before the treatment,and the observation group was higher than the control group.The difference was statistically significant(P<0.05).Compared with the adverse reaction rate of 18.87%in the control group,the observation group was 11.11%,but the difference was not statistically significant(P>0.05).Conclusion:Concurrent chemoradiotherapy for patients with recurrent cervical cancer has a significant effect,which not only can effectively improve the cellular immune index and the survival rate of patients,but also have high safety.

Clinical observation of Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer

Objective:To investigate the efficacy of the Shengxuebao Mixture in treating anemia after concurrent chemoradiotherapy for cervical cancer.Methods:The patients who met the criteria were randomly divided into the study group(n=30)and the control group(n=30).The study group was treated with Shengxuebao Mixture(15 ml once,three times a day)for 30 days,and the control group was treated with ferrous succinate tablets(0.1 g,twice a day),folic acid tablets(5 mg,three times a day),and vitamin B12 tablets(25μg,once a day)for 30 days.Observed the hemoglobin level,erythropoietin level,TCM syndrome score,karnofsky performance status score before and after treatment in the two groups,compared the relevant data and clinical efficacy between the two groups and observed the adverse drug reactions at the same time.Results:The age,pathological type,stage,baseline hemoglobin level,erythropoietin level,TCM syndrome score,and karnofsky performance status score were comparable between the two groups(P>0.05).The hemoglobin level of the two groups after treatment was higher than before treatment(P<0.05).After treatment,the hemoglobin level in the study group was significantly higher than that in the control group(P<0.05),and the number of effective cases in the study group was more than that in the control group,and the effective rate in the study group was higher than that in the control group(P<0.05).The erythropoietin level of the two groups after treatment was lower than before treatment(P<0.05).After treatment,the erythropoietin level in the study group was significantly lower than that in the control group(P<0.05).The TCM syndrome score of the study group decreased significantly after treatment(P<0.05),but there was no significant change in the control group(P>0.05).After treatment,the TCM syndrome score of the study group was significantly lower than that of the control group(P<0.05),and the number of effective cases in the study group was more than that in the control group,and the effective rate in the study group was higher than that in the control group(P<0.05).There was no significant change in the karnofsky performance status score of the study group after treatment(P>0.05),but the karnofsky performance status score of the control group decreased significantly(P<0.05).After treatment,the karnofsky performance status score of the study group was higher than that of the control group(P<0.05),and the number of effective cases in the study group was more than that of the control group,and the effective rate was higher than that of the control group(P<0.05).And there were no obvious adverse reactions in this study.Conclusion:To some extent,this study showed that the Shengxuebao Mixture has a definite effect in treating anemia after concurrent chemoradiotherapy for cervical cancer,can promote the use of erythropoietin,improve TCM syndromes and stabilize the quality of life of patients.

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

Recent achievements and acute toxicity after TP concurrent chemoradiotherapy for the advanced cervical cancer

Objective： The aim of our study was to investigate the early outcome of the taxotere and cisplatin chemora- diotherapy to the advanced cervical cancer. Methods： Fifty-six cases with cervical cancer （FIGO lib to IVa） were divided randomly into two groups in the oncology hospital of Jingzhou from September 2009 to October 2010, radiotherapy alone （28 cases） and radiation plus chemotherapy （TP） group. There was no difference of radiotherapy between the two groups, the RT ＋ C cases who accepted TP regimen during the radiation, and DDP once weekly injection of vain, according to 20 mg/m2 and taxotere once weekly i.v. according to 35 mg/m2. These regimen were given for 4-5 weeks, and some medicine for vomit- ing was given to the RT ＋ C cases. Two groups were received an oral medicine MA 160 mg every day during the treatment. Results： The early outcome： the complete remission rate was 64.3% and partial remission rate was 35.7% in RT ＋ C. The complete remission rate was 32.1% and partial remission rate was 39.3% in RT. The total response rate and complete remis- sion of RT ＋ C group was higher than that of the RT group. There was significant difference between the two groups. In RT ＋ C group, 1-year survive rate was 100.00% （28/28）; in RT group, 1-year survive rate was 85.71% （24/28）. There was significant difference between the two groups （X2 = 4.31 〉 3.84, P 〈 0.05）. Conclusion： The taxotere and cisplatin chemoradiotherapy can improve the early outcome of the advanced cervical cancer, and the adverse effect are raised, but that can be endured.

The early efficacy of the nedaplatin and megestrol combine chemoradiotherapy to the advanced cervical cancers

Objective： The aim of this study was to investigate the early outcome of the nedaplatin and megestrol combine chemoradiotherapy to the advanced cervical cancer. Methods： Forty-two cases with cervical cancer （FIGO lib to IVa） were divided randomly into two groups, radiotherapy alone （RT group： 21 cases） and radiation combines chemotherapy （nedaplatin and megestrol） （RT ＋ C group： 21 cases）. There was no difference of radiotherapy between the two groups, the RT ＋ C group accepted nedaplatin injection during the radiation weekly, according to 30 mg/m^2 ,these regimen were given for 4-5 weeks. This group was received an oral medicine megestro1160 mg every day during the treatment. Results： The RT ＋ C group： the complete remission rate was 80.9% （17/21）, the partial remission rate was 19.1% （4/21）, the effective rate was 100%. The RT group： the complete remission rate was 38.1% （8/21） and partial remission rate was 32.9% （9/21）, the effective rate was 81.0%. The total effective rate and complete remission rate of RT ＋ C group were higher than RT group. There was significant difference between the two groups. The 1-year survival rates respectively were 100% （21/21） in RT ＋ C group, 80.9% （17/21） in RT group. There was statistically significant difference between the two groups （x^2 = 4.42 〉 3.84, P 〈 0.05）. Conclusion： The nedaplatin and megestrol combine chemoradiotherapy can improve the early outcome of the advanced cervical cancer, and the adverse effects was raised, but that can be endured.

Relationship between Cell Proliferation and Apoptosis in Cervical Carcinoma

Objective To study the relationship between cell proliferation and apoptosis in cervical carcinoma and its clinical significance. Methods The cell proliferation and apoptosis of cervical epithelial cells in archival formalin-fixed, paraffin-embedded tissue sections of normal cervix, cervical intraepithelial neoplasms (GIN) and cervical squamous carcinoma were tested by using immunohistochemistry assay and DNA nick end-labeling technigue. The proliferation index (PI) and apoptosis index (AI) were calculated and their correlation with clinical and pathological data was analyzed.Results PI was gradually increased, but the AI and AI/PI ratio decreased from normal cervical epithelium, GIN to cervical carcinoma. There was no significant relationship among cell proliferation, apoptosis, clinical stages and pathological grades. High AI was always associated with a poor prognosis of the patients.Conclusion Cell proliferation and apoptosis allow to distinguish among normal epithelium, GIN and cervical carcinoma and are useful for the assessment of the malignant potential of tumor tissues.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Human Papillomavirus 16 E6,E7 siRNAs Inhibit Proliferation and Induce Apoptosis of SiHa Cervical Cancer Cells

Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results： HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs, which sustained at least 96 h by single dose siRNA. Furthermore, reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion： Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

Objective: To investigate the clinical significance of separate lateral parametrial lymph node dissection(LPLND) in improving parametrial lymph node(PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.Methods: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy(CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.Results: Compared with CRH group, the rate of laparoscopic surgery was higher(60.3% vs. 15.9%, P<0.001),and the blood transfusion rate was lower(19.0% vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases(96.7%) in the LPLND group, and 270 cases(11.6%) in the CRH group(P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group(median 3 vs. 1, P<0.001).The PLN metastases were detected in 25 cases(6.8%) in the LPLND group, and 18 cases(0.8%) in the CRH group(P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio(OR)=228.999, 95% confidence interval(95% CI): 124.661-420.664;P<0.001], but also for PLN metastasis identification(OR=10.867, 95% CI: 5.381-21.946;P<0.001).Conclusions: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.

Relationship between the Expression of Telomerase and Human Papillomavirus Infection in Invasive Uterine Cervical Carcinoma

Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with human papillomavirus （HPV） infection. Histologically confirmed invasive cervical carcinomas and benign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol （TRAP）. The same cases were subjected to polymerase chain reaction （PCR） detection of HPV by using consensus primers and type-specific （HPV types 16 and 18） primers. Telomerase activity was detected in 40 of 45 （88.9%） invasive cervical carcinomas and 2 （all chronic cervicitis） of 50 （4%） benign cervical lesions. HPV was detected in 36 （24 HPV-16 and 4 HPV-18 cases） of 45 （80%） invasive cervical carcinomas and 20 （11 HPV-16 and 1 HPV-18 cases） of 50 （40%） benign cervical changes. There was a significant correlation between the expression of telomerase with histological grade （φ=0.44, P〈0.005）, but no correlation was found between telomerase expression and HPV-18 （P〉0.05）. Although larger sample studies are needed, there seems to be a clear association between telomerase upregulation and HPV status, mainly HPV-16 infection.

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

Objective: To identify the loss of heterozygosity (LOH) on chromosome 17p13 3 in ovarian cancer and cervical cancer Methods: The frequency of LOH on chromosome 17p13 3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non malignant gynecological diseases were determined respectively, using Southern blot method with probe PYNZ 22 Results: LOH on 17p13 3 was found in 12 of 24 (50 0%) ovarian cancers (including a borderline mucinous cystadenoma), 4 of 9 (44 4%) cervical carcinomas, and 1 of 13 (7 7%) non malignant gynecological diseases, which was cervical intraepithelial neoplasm III (CIN III) ( P< 0 01) Conclusion: These results show that LOH on 17p13 3 is associated with ovarian cancer and cervical cancer, suggesting that detection of LOH on 17p13 3 may be helpful to understand the molecular pathogenesis of ovarian cancer and cervical cancer

Aberrant DNA methylation in cervical carcinogenesis

Persistent infection wit h high-risk types of human papillomavirus(HPV) is known to cause cervical cancer;however,additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer.DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis.In this review,we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications.Methylation of the HPV long control region(LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm.The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression.Moreover,promoters of tumor suppressor genes(TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers.Some are associated with squamous cell carcinomas,and others are associated with adenocarcinomas.Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV,atypical squamous cells of undetermined significance,or low grade squamous intraepithelial lesion(LSIL).However,consistent panels must be validated for this approach to be translated to the clinic.Furthermore,reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment,but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.