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PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives

Yumeng Wang, Guiling Li

《医学前沿（英文）》 2019年 第13卷 第4期   页码 438-450 doi: 10.1007/s11684-018-0674-4

摘要： Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-1/PD-L1-related therapeutic strategies for CC.

关键词： PD-1     PD-L1     immune checkpoint blockade antibody     immunotherapy     cervical cancer    

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Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervicalcancer: a randomized, non-inferiority, multicenter trial

《医学前沿（英文）》 2023年 第17卷 第1期   页码 93-104 doi: 10.1007/s11684-021-0892-z

摘要： We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB–IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415–1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

关键词： chemotherapy     cervical cancer     lymph node metastasis     concurrent chemoradiotherapy     quality of life    

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Clinical significance of human papilloma virus infection in the cervical lesions

Shuang LI, Yu-Han MENG, Hu TING, Jian SHEN, Ding MA

《医学前沿（英文）》 2010年 第4卷 第3期   页码 264-270 doi: 10.1007/s11684-010-0094-6

摘要： Cervical lesions have been regarded as the common and frequently occurring diseases in China. Recently, the morbidity and youth tendency of cervical cancer have gradually increased. Cervical cancer, related with human papilloma virus (HPV) infection, has been one of the severest diseases threatening health and life of women, and is an infectious disease. The universality of HPV infection in the reproductive tract should not be ignored. The well-known risk factors of HPV infection in cervical lesions consist of high-risk sexual behaviors, immunosuppression, age, contraceptive methods, the concurrent infection of other sexually transmitted diseases, etc. The variation of cervical lesions induced by HPV infection is involved in the continuous pathological process, including the subclinical, latent, and persistent infection of high risk (HR)-HPV, chronic cervicitis with abnormal results of cytological examination, cervical intraepithelial neoplasia (CIN), and cervical cancer. The outcome of patients with HPV infection is influenced by many factors, such as HPV subtype dominance, persistent HPV infection, HPV loading dose, and multiple HPV infection. Controlling HR-HPV persistent infection should be an important strategy for reducing cervical lesions.

关键词： cervical lesion     high risk-human papilloma virus     persistent infection     loading dose     cervical intraepithelial neoplasia     cervical cancer    

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Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervicalcancer

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 106-112 doi: 10.1007/s11684-014-0307-5

摘要：

Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA--IIA, and SCC IIB--IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated β-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.

关键词： cervical cancer     senescence     Twist     CBX3     lymph node metastasis    

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新疆和田地区49 384例农村妇女宫颈癌检查结果分析

王莹,王小丽,米·斯日尔格楞

《中国工程科学》 2014年 第16卷 第5期   页码 96-98

摘要：

分析和田地区子宫颈癌检查项目资料，了解当地妇女宫颈癌的发病情况，针对项目工作提出改进措施，提高农村妇女健康水平。本文采用整群抽样的方法，为项目地区的适龄妇女开展子宫颈癌流行病学调查，提供临床检查服务。结果显示，和田地区妇女患病率为49.62 %，宫颈炎和阴道炎是主要的妇科疾病，宫颈癌和癌前病变患病率为0.09 %，早期诊断率为86.05 %。和田地区妇女健康状况较差，当地妇女自我保健意识不高，当地医疗保健机构宫颈癌筛查能力有待提高。

关键词： 子宫颈癌     新疆     妇女病    

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relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis in cervicalcancer

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 447-451 doi: 10.1007/s11684-009-0082-x

摘要： This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and- D were all higher in the experimental group than in the control group (<0.05); no significant difference was found in the expression of PDGF-C between the experimental group and the control group (>0.05). PDGF-A and -B expression was positively related with BVD and LVD (<0.01, R= 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.

关键词： cervical cancer     lymphatic vessel density     blood vessel density     platelet-derived growth factor    

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Epidemiological studies of women under age 30 infected with human papillomavirus

Zhihua LIU MD, Qing LI BM, Weihong LI BM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 459-462 doi: 10.1007/s11684-009-0084-8

摘要： The aim of this paper was to investigate the prevalence of human papilloma virus (HPV) infection in women under 30 years old with cervical intraepithelial neoplasia (CIN) or cervical cancer, in order to provide a basis for cervical cancer prevention and treatment. We recruited 2052 female cases from the education system in Futian District, Shenzhen city, from April 2006 to April 2008, with age ranging from 22 to 60 years old. Second-generation hybrid capture test was done for detection of female genital tract HPV and cervical colposcopy for screening CIN or cervical cancer. The prevalence of HPV and cervical precancerous lesions or cervical cancer was evaluated in different age groups of women. The HPV positive rate was 247/2052 (12.00%), and 35/2052 (1.71%) of the cases were≥CIN I by pathological diagnosis. In the 22―29-year-old age group, there were 291 cases, including 39HPV-positive cases (13.40%) and one case of pathological diagnosis≥CIN I (0.34%), and there were 1761 cases in the 30―60-year-old age group, including 208 HPV-positive cases (11.81%) and 34 cases of pathological diagnosis≥CIN I (1.93%). The HPV-positive rate of 22―29-year-old age group was higher than that of 30―60-year-old age group, but the difference was not significant ( = 0.5967, = 0.4398); the CIN and cervical cancer detection rate of the former group was lower than that of the latter one, and the difference was not significant either ( = 3.7519, = 0.0527). The cases in 30―60-year-old age group were divided into five age sub-groups, and the HPV-positive rate of the 22―29-year-old age group was compared with the remaining groups, and it was found that the HPV-positive rate of the former group (13.40%) was lower than that of the 40―44-year-old age group (14.70%) but higher than that of the other four groups. Moreover, the difference in the HPV-positive rate between the 22―29-year-old age group and the 50―60-year-old age group (6.06%) was significant ( = 5.545, = 0.018), but the difference between the 22― 29-year-old age group and each of the other four groups was not significant (>0.05). In addition, the CIN and cervical cancer detection rate of the 22―29-year-old age group (0.34%) was lower than that of the remaining five groups, and the difference between the 22―29-year-old age group and the 35―39-year-old age group (2.26%), and between 22―29-year-old age group and 40―44-year-old age group (2.30%) was significant ( = 4.446, = 0.0035; = 4.525, = 0.0363, respectively), but the difference between the 22―29-year-old age group and each of other three groups was not significant (>0.05). Furthermore, 80.00% (28/35) cases of pathological diagnosis≥CIN I and 90.91% (10/11) lesions of pathological diagnosis≥CIN II occurred at 35―49 years of age. For many young women below the age of 30 who were infected with high-risk HPV were one-off infections, so it was not appropriate to recommend HPV detection as cervical precancerous lesions or cancer screening program for women less than 30 years old. The prevention and treatment of cervical cancer should be focused on those women more than 35 years of age.

关键词： cervical cancer     human papilloma virus     cervical intraepithelial neoplasia    

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Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 341-346 doi: 10.1007/s11684-009-0067-9

摘要： Phosphatidylinositol 3-kinase (PI3K) is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis. This study was to investigate the regulation of proliferation and apoptosis by LY294002, an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein (c-FLIP) . Human cervical cancer HeLa cells were used in this experiment and cultured. The cultured cells were treated with LY294002 at different concentrations (10, 25, 50 and 100µmol/L) for 6, 12, 24, and 48h before harvesting for evaluation. Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay. Apoptosis was analyzed by flow cytometry. The expression of c-FLIP was detected by Western blot. Cell viability was inhibited by LY294002 significantly (<0.05). Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group. Although the expression of c-FLIP was increased in a short time, the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48h. These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells. Moreover, the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed .

关键词： human cervical cancer cells     apoptosis     phosphatidylinositol 3-kinase (PI3K)/Akt     FLICE-like inhibitory protein    

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HPV prevalence and genotyping in the cervix of Chinese women

Shao-Ming WANG, Jing LI, You-Lin QIAO

《医学前沿（英文）》 2010年 第4卷 第3期   页码 259-263 doi: 10.1007/s11684-010-0095-5

摘要： The role of human papillomavirus (HPV) as an etiologic factor of cervical cancer has been firmly established, and prophylactic vaccines are now available and have been approved in many countries. Vaccination implies a promising future for cervical cancer prevention especially for countries with very limited access to screening. However, the vaccines are not accessible in mainland China at the moment, and much needs to be understood about the potential benefit when HPV vaccines are applied to Chinese women, and to make the vaccines more specific to Chinese women. This article reviews advanced multi-center, hospital/population-based studies of most recent years, and aims to draw a definitive conclusion on HPV prevalence and genotyping in cervical cancer and precancerous lesions in China from the aspect of study population, geographic areas and time period.

关键词： human papillomavirus (HPV) genotyping     cervical cancer     precancerous lesions     Chinese women    

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Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled trial

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 112-116 doi: 10.1007/s11684-010-0016-7

摘要： We conducted a trial to assess the influence of closure or nonclosure of the peritoneum and subcutaneous tissue on the clinical outcomes of cervical cancer patients who underwent radical hysterectomy with lower abdominal cross incision. This randomized controlled trial was performed on 158 cervical cancer patients in our hospital between January 2002 and June 2004. Eighty-two patients were allocated to the “closure” group and 76 patients to the “nonclosure” group. Results showed that non-closure of the peritoneum and subcutaneous tissue could shorten operation time and febrile duration, reduce antibiotics requirement, increase the volume of drainage and decrease the incidence of liquefaction of subcutaneous fat (<0.05). There was no difference in blood loss, postoperative complications, bowel function restoration and post-operative stay between the two groups (>0.05). Our study revealed that closure of the peritoneum and subcutaneous tissue provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anesthesia exposure. The practice of closure of the peritoneum and subcutaneous tissue at radical hysterectomy should be questioned.

关键词： cervical cancer     radical surgery     peritoneum     subcutaneous tissue    

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A new thinprep cytologic test of cervical cells and its application

Xiaojun ZHAO, Jingjuan WEI, Rong WANG, Yajun GU, Yunde LIU

《医学前沿（英文）》 2009年 第3卷 第2期   页码 227-229 doi: 10.1007/s11684-009-0035-4

摘要： In order to improve the quality of routine cervical smears, we investigated the new Thinprep cytologic test (TCT) for cervical cells. In this study, 100 women who were enrolled were randomly divided into two groups. In one group, the TCT for cervical cells was applied (TCT group), and in the other group routine cervical smear was used. In addition, the cells in the TCT group were screened by double sifters, and centrifuged using a separation medium so as to eliminate mucus, inflammatory cells and blood cells. According to the cell distribution and the thickness of the smear, the results were assigned to three groups, including satisfactory smears, less satisfactory smears and unsatisfactory smears. The TCT had a higher satisfactory rate (98%) compared to the routine cervical smear (32%) ( <0.01), indicating the TCT was superior to the routine cervical smear. It is concluded that the TCT is more acceptable. Meanwhile, in comparison to the routine cervical smear, the TCT for cervical cells has 5 advantages which can greatly increase the cytological accuracy.

关键词： thinprep cytologic test     cervical cells     Papanicolaou smear    

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Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 223-228 doi: 10.1007/s11684-017-0517-8

摘要：

The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion (HSIL) patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 (47.06%) patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma (3 stage IA1 and 1 stage IA2 patients). Univariate analysis showed that patient age>35 years (P=0.005), menopausal period>5 years (P=0.0035), and multiple-quadrant involvement (P=0.001) were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement (P=0.001; OR, 3.701; 95%CI, 1.496–9.154) was an independent risk factor for residual disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider re-conization or re-assessment.

关键词： cervical high-grade squamous intraepithelial lesion     conization     positive surgical margin     hysterectomy    

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Anterior cervical surgery methods for central cord syndrome without radiographic spinal fracture-dislocation

Chengwei JING, Qin FU, Xiaojun XU

《医学前沿（英文）》 2009年 第3卷 第1期   页码 45-48 doi: 10.1007/s11684-009-0019-4

摘要： This study was aimed to explore the anterior cervical surgery methods to treat central cord syndrome without radiographic spinal fracture-dislocation (CCSWORFD), retrospectively analyze the cases of CCSWORFD, and evaluate the curative effect of anterior cervical surgery methods for CCSWORFD. Twenty four cases of CCSWORFD (19 males and 5 females), all suffering from cervical hyperextension injury, between 45-68 (average 59) years old, were operated on by anterior cervical surgery methods. Among these, 18 cases had been followed up for 6-24 (average 15) months; 18 cases, who had anterior decompression and plate fixation with titanium mesh bone grafting or iliac bone grafting achieved reliable effects based on the Japanese Orthopedics Association (JOA) evaluation (improved scores of cases with titanium mesh bone grafting, = 2.800, <0.05; improved scores of cases with iliac bone grafting, = 3.270, <0.05), and reliable reconstruction of cervical spine. The two groups obtained the same curative effect ( = 0.470, >0.05) Most of these cases had degeneration of cervical vertebra. The decompression which relieves the oppression to the spinal cord can help lessen edema of the spinal cord, and early fixation for stability of cervical vertebra is better for the recovery of spinal cord injury. Anterior operation with titanium mesh bone grafting or iliac bone grafting are both reliable curative methods for CCSWORFD, and titanium mesh bone grafting can avoid the trauma of the supplying graft. Mesh bone grafting can also shorten hospital stay.

关键词： central cord syndrome     decompression     surgical     titanium mesh    

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Differential diagnosis of cervical nerve compression syndrome of the external intervertebral foramen

WANG Jinwu, NI Weifeng, XU Jianguang, ZHU Haibo, GUO Shangchun, ZENG Bingfang, ZHAO Binghui

《医学前沿（英文）》 2007年 第1卷 第2期   页码 177-180 doi: 10.1007/s11684-007-0033-3

摘要： The aim of the present research is to study the mechanism of cervical nerve compression syndrome of the external intervertebral foramen and its differential diagnosis with cervical spondylosis. Diagnostic treatment with muscle relaxant, vasodilator, neurotrophic medicine and celecoxib (COX)-2 inhibitor were performed in 20 patients with cervical nerve compression syndrome of the external intervertebral foramen and 20 patients with cervical spondylosis confirmed by operation. Diagnostic local block therapy was performed additionally in cases showing little effect after diagnostic treatment. All the patients were followed up postoperatively for more than one year. Fifteen cases with cervical nerve compression syndrome of the external intervertebral foramen were healed by the diagnostic treatment. The other five cases had a short-term remission and there was no recurrence after diagnostic local block therapy. Diagnostic treatment led to short-term alleviation of the symptom in 20 cases with cervical spondylosis confirmed by operation, the results of which was far from satisfactory and operation was undertaken finally in all the 20 cases. The etiology of cervical nerve compression syndrome of the external intervertebral foramen lies in the compression of the cervical plexus, brachial plexus and cervical dorsal rami by the tendinous decussating fibers of the scalenus anticus, medius, minimus and the posterior muscles of the neck. Diagnostic treatment was propitious to differentiate cervical nerve compression syndrome of the external intervertebral foramen from cervical spondylosis.

关键词： satisfactory     COX     minimus     operation     compression syndrome    

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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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标题 作者 时间 类型 操作

PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives

Yumeng Wang, Guiling Li

期刊论文

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervicalcancer: a randomized, non-inferiority, multicenter trial

期刊论文

Clinical significance of human papilloma virus infection in the cervical lesions

Shuang LI, Yu-Han MENG, Hu TING, Jian SHEN, Ding MA

期刊论文

Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervicalcancer

null

期刊论文

新疆和田地区49 384例农村妇女宫颈癌检查结果分析

王莹,王小丽,米·斯日尔格楞

期刊论文

relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis in cervicalcancer

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

期刊论文

Epidemiological studies of women under age 30 infected with human papillomavirus

Zhihua LIU MD, Qing LI BM, Weihong LI BM,

期刊论文

Effects of phosphatidylinositol 3-kinase inhibitor on human cervical carcinoma cells

Yuan ZHANG MD , Xiaoyan ZHANG MM , Yanhui LI MM , Xuan DU MM , Zehua WANG MD, PhD , Hongbo WANG MD ,

期刊论文

HPV prevalence and genotyping in the cervix of Chinese women

Shao-Ming WANG, Jing LI, You-Lin QIAO

期刊论文

Non-closure of the peritoneum and subcutaneous tissue at radical hysterectomy: A randomized controlled trial

Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,

期刊论文

A new thinprep cytologic test of cervical cells and its application

Xiaojun ZHAO, Jingjuan WEI, Rong WANG, Yajun GU, Yunde LIU

期刊论文

Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin

null

期刊论文

Anterior cervical surgery methods for central cord syndrome without radiographic spinal fracture-dislocation

Chengwei JING, Qin FU, Xiaojun XU

期刊论文

Differential diagnosis of cervical nerve compression syndrome of the external intervertebral foramen

WANG Jinwu, NI Weifeng, XU Jianguang, ZHU Haibo, GUO Shangchun, ZENG Bingfang, ZHAO Binghui

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文