Cases Of Cervical Carcinoma Research Articles

Cervical small cell carcinoma frequently presented in multiple high risk HPV infection and often associated with other type of epithelial tumors

BackgroundSmall cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk HPV infections.MethodsThe clinicopathological data of 30 cases of cervical primary small cell carcinoma were retrospectively analyzed. In situ hybridization, polymerase chain reaction and reverse dot-blot hybridization were employed to detect HPV DNA in both small cell carcinoma and other coexisting epithelial tumors. Immunohistochemistry was used to detect the protein expression of p16 and p53.ResultsAmongst 30 patients with cervical primary small cell carcinoma, 15 patients simultaneously exhibited other types of epithelial tumors, including squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma in situ, and adenocarcinoma in situ. Most tumor cells infected with HPV presented integrated patterns in the nuclei by in situ hybridization. HPV DNA was detected in every small cell carcinoma case (100%) by polymerase chain reaction and reverse dot blot hybridization. 27 cases (90%) harbored type 18, and 15 (50%) displayed multiple HPV18 and 16 infections. The prevalence of HPV 18 infection in small cell carcinoma was higher than in cervical squamous and glandular epithelial neoplasms (P = 0.002). However, similar infection rates of HPV 16 were detected in both tumors (P = 0.383). Both small cell carcinoma and other types of epithelial tumors exhibited strong nuclear and cytoplasmic staining for p16 in all cases. Three cases of small cell carcinoma revealed completely negative p53 immunohistochemical expression in 15 cases of composite tumors, which suggested TP53 nonsense mutation pattern. The pure small cell carcinoma of uterine cervix had similar mutation or wild type pattern for TP53 compared with composite tumor (P = 0.224).ConclusionsCervical small cell carcinomas are often associated with squamous or glandular epithelial tumors, which might result from multiple HPV infections, especially HPV 16 infection. Multiple HPV infections were not correlated with tumor stage, size, lymphovascular invasion, lymph node metastasis, or prognosis. Furthermore, careful observation of specimens is very important in finding little proportion of small cell carcinoma in the composite lesions, specifically in cervical biopsy specimens, in order to avoid the missed diagnosis of small cell carcinoma.

Prognostic Significance of Vascular Endothelial Growth Factor (VEGF) and Her-2 Protein in the Genesis of Cervical Carcinoma.

BACKGROUND:Angiogenesis plays a pivotal role in the progression of tumours through the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a chief factor responsible for inducing and regulating angiogenesis. Additionally, the human epidermal growth factor receptor family of receptors also plays an important role in the pathogenesis of tumours.AIM:This study aimed to examine the association between VEGF and Her-2 protein expression and its correlation with clinic-pathological characteristics; in particular, prognosis.METHODS:A total of 65 cases of cervical carcinoma and 10 samples of inflammatory lesions were evaluated for VEGF and Her-2 protein expression.RESULTS:Expression of VEGF and Her-2 was detected in 63.07% and 43.07% in cervical carcinoma cases respectively whereas control cases did not show any expression. The difference in the expression pattern of both markers comparing cancer and control cases was statistically significant (p < 0.05). However, no significant difference in the expression pattern of VEGF protein was observed among the different grades and stages of tumours (p > 0.05). Comparing different grades of a tumour, expression of Her-2 was detected in 31.8% of well-differentiated tumours, 36.0 % in moderately differentiated tumours and 66.66 % in poorly differentiated cancers. The expression of Her-2 was increased in high-grade tumours, and the difference of expression level between tumour grades was statistically significant (p < 0.05). The expression level of Her-2 protein was not correlated with the stage of a tumour (p > 0.05).CONCLUSION:The present study supports earlier findings that over-expression / up-regulation of VEGF and Her - 2 is linked with poor prognosis and may play a vital role in the development and progression of cervical cancer.

MicroRNA-409 inhibits the proliferative ability of cervical carcinoma cells by regulating AKT.

To observe the microRNA-409-3p expression in cervical carcinoma and its effect on the growth and proliferative ability of cervical carcinoma cells. The microRNA-409-3p level in 62 cases of cervical carcinoma and 38 cases of normal cervical tissue was detected by qRT-PCR. The association between the microRNA-409-3p level and clinicopathological features of cervical carcinoma was investigated. Knockdown and overexpressed microRNA-409-3p in cervical carcinoma cells, HeLa and SiHa, were used to detect the cell cycle and the activity of cervical carcinoma cells. Subsequently, potentially target genes of microRNA-409-3p were predicted by bioinformatics website. Western Blot and luciferase assay were used to confirm their correlation. We observed a significant lower microRNA-409-3p level in cervical carcinoma tissues than that in normal cervical tissues. Significant correlation was found between the microRNA-409-3p level in patients with cervical carcinoma and the overall survival rate, tumor size and TNM stage (p<0.05), but correlations with age, pathological type and lymph node metastasis were not found (p>0.05). After silencing the expression of microRNA-409-3p in cervical carcinoma cells, the proliferative ability of cervical carcinoma cells was greatly promoted. In addition, microRNA-409-3p was targeting on protein kinase B (AKT) and had a negative correlation with AKT expression. The microRNA-409-3p level was lower in cervical carcinoma tissues, and was significantly affected the overall survival, tumor size and TNM staging in clinical patients. Low expression of microRNA-409-3p could promote the proliferative ability of cervical carcinoma cells through the target gene AKT.

Study of Her2/neu expression in 100 cases of uterine and cervical carcinoma as a prognostic marker

Background: HER-2/neu, is a gene localized on chromosome 17q21 that encodes a growth factor receptor like molecule with tyrosine- kinase activity. Its expression has been detected in several human cancers and is believed potential. Aim of our study was to evaluate the expression of Her-2/neu oncogene in uterine & cervical carcinomas and determine its correlation with histological type of malignancy, grade and clinical stage of presentation. Methods: Total 100 cases were studied, out of which there was 22 cases of uterine tumour and 78 cases of cervical tumours. The specimens were processed routinely ,stained with standard H&E method and relevant panel of immunohistochemical antibodies were applied (PAP -peroxidase anti- peroxidase method )after thorough histopathological analysis. Result: Her-2/neu was expressed by 3 (13.6%) out of 22 cases of uterine adenocarcinomas while in cases of cervical carcinomas 9 (11.53%)1 out of 78 cases express Her-2neu . In cervical carcinoma, 50% cases of squamous cell carcinomas, 20% poorly differentiated carcinomas, 18.1% well differentiated carcinomas and 3.4% of moderately differentiated carcinomas express Her-2/neu positivity. Conclusion: We have found that Her-2/neu can be used as a prognostic marker in uterine carcinoma and its expression increases with increase in stage and grade of endometrial adenocarcinoma. Her2/ neu has little utility in cervical carcinomas and is not correlated with its grading and staging.

Distinct Changes in the Expression TAZ are Associated with Normal Cervix and Human Cervical Cancer.

The transcriptional coactivator with the PDZ-binding motif (TAZ) has been associated with different types of cancer. In this study, we examined the TAZ protein expression and cellular localization in 194 cases of human cervical squamous cell carcinoma (SCC). We observed that a normal cervix is characterized by higher expression levels of both nuclear and cytosolic TAZ compared to cervical SCC. Lower membranous and cytosolic TAZ expression levels are associated with lymph node involvement. We observed that TAZ expression levels are associated with β1 integrin and Src in SCC and cell lines derived from human cervical cancers. Of note, knock down of TAZ increased the expression of β1 integrin and Src in both normal and human cervical cancer cells. Our data indicate that the expression and cellular localization of TAZ are inversely associated with the development and progression of cervical SCC, and TAZ-mediated transcription may be involved in the activation of the integrin-Src signalling pathway.

Study on clinical management of HPV(+)/Pap(-) during cervical cancer screening

Objective: To study the clinical management way for HPV(+)/papanicolaou (Pap)(-) during cervical cancer screening. Methods: To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN) Ⅱ in Peking University People's Hospital from Jan. 2010 to Dec. 2014. Results: (1) For biopsy confirmed CIN Ⅱ, HPV positive rate was 98.5% (135/137), Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137), there was significant difference between them (χ(2)=43.32, P<0.01). (2) For the 42 patients with HPV(+)/Pap(-), whose cytology slides were reviewed again. Among them, the interpretations of there were 16 cases confirmed as the same before, while 26 cases were changed to abnormal (≥ASCUS). Cytology be misdiagnosed was 19.0% (26/137) at the first review. Among the 26 cases, 13 (50.0%) cases were missed for the little amount of abnormal cells, 8 (30.8%) cases for mild atypical morphology changed; the other 5 (19.2%) cases missed for stain problems. (3) For the cervical LEEP samples, 37 cases of the pathology diagnosis were upgrade to CIN Ⅲ(+), among them, 2 cases of microinvasive cervical carcinoma, 1 case of invasive cancer, 34 cases of CIN Ⅲ; 37 cases were CINⅠ or no lesion found; 63 cases were still CIN Ⅱ. Four to six months later after LEEP, the cytology abnormal rate was 11.7% (16/137), and the HR-HPV positive rate was 34.3% (47/137). Conclusions: Compared with cytology alone, cytology combined with HPV testing increase the sensitivity of cervical high grade lesion. For the cases of HPV(+)/Pap(-) cases, the cytology slides should be reviewed. The quality control of cervical exfoliate sample collection and interpretation should be strengthened. LEEP procedure is not only a treatment method, but also it could provide samples to confirm the diagnosis.

Y Box-Binding Protein 1 Promotes Epithelial-Mesenchymal Transition, Invasion, and Metastasis of Cervical Cancer via Enhancing the Expressions of Snail.

Y box-binding protein 1 (YB-1) is a potent oncogenic protein. How it regulates Snail in most tumors including cervical cancer is unknown. This article is to study if YB-1 plays a role in cervical cancer via regulating the expression of Snail. Immunohistochemical staining of YB-1, Snail, and E-cadherin (E-cad) was performed on tissue specimens including 35 cases of chronic cervicitis (as a control), 35 cases of cervical intraepithelial neoplasm (CIN) I, 35 cases of CIN II/III, 28 cases of unmetastatic cervical squamous cell carcinoma, and 19 cases of metastatic cervical squamous cell carcinoma. RNA interference technique was used to knock down YB-1, E6, and Snail genes. Quantitative polymerase chain reaction, western blot, and transwell experiment were used to detect RNA, protein, and cell invasion of cervical cancer cell lines Hela and C33A, respectively. First, YB-1 knockdown significantly reduced messenger RNA (mRNA) and protein levels of Snail, followed by the increased mRNA and protein levels of E-cad and the decreased invasive ability in both Hela (human papillomavirus [HPV] 18+) and C33A (HPV-) cell lines. Second, YB-1 and Snail protein were correlatively expressed in the group order of metastatic cervical squamous cell carcinoma > unmetastatic cervical squamous cell carcinoma > CINs > cervicitis, with the inverse expression mode of E-cad in the group order, P value less than 0.01, between any 2 groups. Finally, HPV18 E6 knockdown reduced the mRNA and protein levels of YB-1 and Snail in Hela cells. The results firstly reported that YB-1 whose mRNA expression is regulated by HPV18 E6 promotes epithelial-mesenchymal transition and progression of cervical cancer via enhancing the expressions of Snail, which indicated that YB-1/Snail/epithelial-mesenchymal transition axis could have a potential use in the diagnosis and therapy of cervical cancer metastasis as a cancer marker and molecular target.

Negative correlation between X-linked inhibitors of apoptosis and second mitochondria-derived activator of caspase expression levels in cervical carcinoma and cervical intraepithelial neoplasia.

X-linked inhibitors of apoptosis (XIAP) and second mitochondria-derived activator of caspase (Smac) have been widely reported to serve roles in the development of cervical carcinoma. The present study analyzed the associations between the expression levels of XIAP and Smac in normal cervical epithelium, cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Immunohistochemistry staining of formalin-fixed, paraffin-embedded tissue sections was performed in order to analyze the expression levels of XIAP and Smac in 15 cases of normal cervical tissues, 69 cases of CIN and 76 cases of cervical carcinoma. All the tissue samples were confirmed by pathological diagnosis. The association of XIAP and Smac expression levels was analyzed using one-way analysis of variance, χ2 tests and Spearman's ρ for the nonparametric bi-variant correlation analysis. Overall survival was determined using the log-rank test and Kaplan-Meier survival curves. The expression level of XIAP was increased in CIN and cervical carcinoma tissues compared with normal cervical tissues, whereas Smac demonstrated a converse expression pattern to XIAP in these tissues. The positive staining level of XIAP protein was increased in grade 3 CIN compared with that in grade 1–2 CIN, and was significantly higher in the less-differentiated tissue of cervical carcinoma compared with the well- or medium-differentiated tissues (P<0.05). The staining level was also significantly increased in cervical carcinoma with stage 2b-3 compared with tissues from stage 1–2a carcinoma (P<0.05). The expression levels of Smac were in opposition to these results. XIAP was associated with pelvic lymph node metastasis, whereas no association was identified with Smac expression. The expression level of XIAP was significantly and negatively associated with cell survival time in cervical carcinoma, whereas the expression level of Smac was significantly and positively associated with cell survival time in cervical carcinoma. Therefore, XIAP and Smac may participate in the development of cervical cancer. The expression levels of XIAP and Smac were significantly and inversely associated. This may be useful in early diagnosis, evaluation of surgery and chemotherapy and the prognosis of cervical carcinoma.

EP28.02: Two cases of growing inwardly uterine cervical carcinoma that were diagnosed by transvaginal ultrasound guided needle biopsy

In diagnosis of uterine cervical carcinoma growing inwardly with biopsied specimens, accurate pathological diagnosis may not be provided because only an outer layer region of tumour is obtained. We report two cases of uterine cervical carcinoma that was diagnosed by transvaginal ultrasound guided needle biopsy. Two cases were cervical carcinoma which had difficulty in diagnosis by punch biopsied specimens though invasive carcinomas were suspected clinically with MRI findings. Case 1.A 49-year-old 3 gravidas 2 parous woman was referred to our hospital because of abnormal genital bleeding. MRI showed 67mm uterine cervical tumour, and cytology of uterine cervix was SCC. Subsequently, punch biopsy for cervical tumour was performed, but pathological diagnosis with obtained specimens was cervical intraepithelial neoplasia 3(CIN3). Therefore we performed transvaginal ultrasound guided needle biopsy, the result was that the diagnosis of invasive squamous cell carcinoma was obtained in grounds for the existence of atypical squamous cells infiltrating to myometrial layer. Case 2.A 38-year-old 4 gravidas 4 parous woman with past history of tubal ligation was referred to our hospital because of abnormal genital bleeding. MRI showed 38mm uterine cervical tumour, and cytology of uterine cervix was SCC. Subsequently, punch biopsy and diagnostic conisation for cervical tumour were performed, but pathological diagnosis by both examination was cervical intraepithelial neoplasia 3(CIN3). Therefore we performed transvaginal ultrasound guided needle biopsy, the result was that the diagnosis of invasive squamous cell carcinoma was obtained. It was thought that diagnosis by needle biopsied specimens was useful for growing inwardly uterine cervical carcinoma. In addition, it was thought that specimens could be obtained safely even if they were from deep region by performing needle biopsy under transvaginal ultrasound guide.

PREVALENCE OF HUMAN PAPILLOMA VIRUS TYPES 16 AND 18 AMONG WOMEN WITH CERVICAL CANCER IN ALEPPO, SYRIA

Objective: Cervical cancer is the second common type of cancer among women worldwide. Infection by certain types of human papillomavirus infection (HPV) such as HPV 16/18 has been considered as the most significant risk factor for the development of cervical cancer. This study was conducted to determine the prevalence HPV 16/18 in women with and without cervical cancer in Aleppo city, Syria.Methods: Paraffin embedded cervical tissue samples were collected from 113 patients and 40 controls (normal cervix), DNA was extracted and analyzed by PCR for the presence of HPV16/18. Out of 113 cases of cervical carcinoma, 25 cases (22.1%) were carcinoma in situ (CIS), 72 cases (63.7%) were squamous cell carcinomas (SCC) and 16 cases (14.2%) were adenocarcinoma (ADC).Results: HPV 16 and/or 18 DNA was detected in 84 (74.3%) cases out of 113 of cervical cancers, while it was found in only two of the 40 samples in the control group. At the same time, 9 out of 25 (36%) carcinoma in situ, 61 out of 72(84.72%) squamous cell carcinomas, and 14 out of 16 (87.5%) adenocarcinomas, were positive for HPV 16 and/or 18.Conclusion: The frequency of infection with HPV 16 and 18 is high among Syrian women and a vaccine against these two types may be effective in about 74% of cervical cancers in Syria.

Mutational analysis of the RAS/RAF/MEK/ERK signaling pathway in 260 Han Chinese patients with cervical carcinoma.

Prevalent mutations in the mitogen-activated protein kinase 1 (MAPK1)/extracellular signal-regulated kinase 2 (ERK2) pathway have been identified in cervical squamous cell carcinoma in a large-scale genome sequencing effort. Furthermore, mutations in the rat sarcoma viral oncogene homolog (RAS)/Raf/Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway have also been revealed to have important roles in the pathogenesis of human cancer. However, whether the potential hotspot mutations in ERK2 and other components of the RAS/RAF/MEK/ERK signaling pathway also exist in Chinese patients with cervical carcinoma remains to be elucidated. In the present study, a total of 260 patients with cervical carcinoma of distinct subtypes were analyzed for the presence of potential hotspot mutations in the RAS/RAF/MEK/ERK signaling pathway. No ERK2 mutations were detected in these samples; however, Kirsten RAS (KRAS) p.G12D (c.35G>A) mutation was identified in 2/26 (7.7%) cervical adenocarcinoma cases, including 1/20 cervical mucinous adenocarcinoma and 1/6 cervical endometrioid carcinoma cases. In addition, no mutations in the ERK1, neuroblastoma RAS, Harvey RAS or B-Raf proto-oncogene serine/threonine kinase genes were detected in the present study. These results indicated that ethnic differences may be a primary reason for the discrepancy in ERK2 mutation frequencies between the current study and previous studies. Furthermore, mutation in the KRAS gene, but not other genes in the RAS/RAF/MEK/ERK signaling pathway, may have an active role in the pathogenesis of cervical carcinoma.

Application of immunohistochemistry for p16 and GATA3 and molecular HPV typing in diagnosis of secondary bladder involvement by cervical carcinoma

Objective: To investigate the expression of p16 and GATA3 and the detection of human papillomavirus (HPV) in secondary bladder involvement by cervical carcinomas. Methods: Sixteen cases of cervical carcinoma with bladder involvement diagnosed from December 2008 to March 2016 were collected and evaluated by light microscopy, immunohistochemistry for p16 and GATA3 detection and PCR-reverse dot blot for molecular typing of HPV. Results: The age of the patients ranged from 25 to 76 years with median of 52 years. Morphologically, 14 cases(14/16) showed tumor nests infiltrating lamina propria or muscle bundles of the bladder. By immunohistochemistry, 15 cases (15/16) were found to be diffusely and strongly positive for p16, and 1 showed patchy staining pattern. Seven cases (7/7) of corresponding original cervical cancers were also diffusely and strongly positive for p16. GATA3 staining was negative in 13 cases (13/16), and focal weak to moderate positivity was detected in 3 cases.Three cases (3/7) of corresponding original cervical cancers showed focal weak to moderate positivity of GATA3. Fifteen cases (15/16) showed concordant high risk HPV-positivity, including HPV16 in 8 cases and HPV31 in one case. Five cases showed co-infection of HPV16 and HPV18. One case showed co-infection with HPV18 and HPV45. Conclusion: Differential diagnosis by p16 or GATA3 alone is of limited value. Combination of immunohistochemistry for p16 and GATA3 and molecular typing for HPV detection are useful to distinguish primary bladder carcinoma from the secondary involvement by cervical carcinoma.

Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin by conization: a retrospective analysis.

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 reconization or re-assessment.

An integrated strategy of biological and physical constraints in biological optimization for cervical carcinoma

BackgroundFor cervical carcinoma cases, this study aimed to evaluate the quality of intensity-modulated radiation therapy (IMRT) plans optimized by biological constraints. Furthermore, a new integrated strategy in biological planning module was proposed and verified.MethodsTwenty patients of advanced stage cervical carcinoma were enrolled in this study. For each patient, dose volume optimization (DVO), biological model optimization (BMO) and integrated strategy optimization (ISO) plans were created using same treatment parameters. Different biological models were also used for organ at risk (OAR) in BMO plans, which include the LKB and Poisson models. Next, BMO plans were compared with their corresponding DVO plans, in order to evaluate BMO plan quality. ISO plans were also compared with DVO and BMO plans, in order to verify the performance of the integrated strategy.ResultsBMO plans produced slightly inhomogeneity and less coverage of planning target volume (PTV) (V95=96.79, HI = 0.10: p < 0.01). However, the tumor control probability (TCP) value, both from DVO and BMO plans, were comparable. For the OARs, BMO plans produced lower normal tissue complication probability (NTCP) of rectum (NTCP = 0.11) and bladder (NTCP = 0.14) than in the corresponding DVO plans (NTCP = 0.19 and 0.18 for rectum and bladder; p < 0.01 for rectum and p = 0.03 for bladder). V95, D98, CI and HI values that were produced by ISO plans (V95 = 98.31, D98 = 54.18Gy, CI = 0.76, HI = 0.09) were greatly better than BMO plans (V95 = 96.79, D98 = 53.42Gy, CI = 0.71, HI = 0.10) with significant differences. Furthermore, ISO plans produced lower NTCP values of rectum (NTCP = 0.14) and bladder (NTCP = 0.16) than DVO plans (NTCP = 0.19 and 0.18 for rectum and bladder, respectively) with significant differences.ConclusionsBMO plans produced lower NTCP values of OARs compared to DVO plans for cervical carcinoma cases, and resulted in slightly less target coverage and homogeneity. The integrated strategy, proposed in this study, could improve the coverage, conformity and homogeneity of PTV greater than the BMO plans, as well as reduce the NTCP values of OARs greater than the DVO plans.

Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma

BackgroundThe disequilibrium of local immune microenvironment is an essential element during tumorigenesis.MethodBy conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix.ResultThe FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection.ConclusionOur data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis.Trial registrationNot applicable.

Pathological characteristics and immunophenotype analysis of cervical intraepithelial neoplasia

Abstract Objective To explore the clinical pathological features and immunophenotypes of cervical intraepithelial neoplasia (CIN). Methods The protein expression of p16, p53, Bcl-2, and c-erbB-2 in 59 cases of CIN, 20 cases of cervical squamous cell carcinoma, and 20 cases of normal cervical tissues were tested using immunohistochemistry staining. Results The expression rates of p16, p53, Bcl-2, and c-erbB-2 in CIN tissues were 76.3% (45/59), 28.85 (17/59), 61.0% (36/59), and 40.0% (23/59), respectively. The expression rates of p16, p53, Bcl-2, and c-erbB-2 in cervical squamous cell carcinoma tissues were 60.0% (12/20), 60.0% (12/20), 75.0% (15/20), and 65.0% (13/20), respectively. The expression rates of p16, p53, Bcl-2, and c-erbB-2 in normal cervical tissues were 0.0% (0/20), 0.0% (0/20), 35.0% (7/20), 0.0% (0/20), respectively. In comparison to normal tissues, the differential expressions of p16, p53, and Bcl-2 in squamous cell carcinoma and CIN were statistically significant (P &lt;0.001), whereas the difference between the squamous cell carcinoma and CIN was not significant (P &gt;0.05). In comparison to normal tissues, the differential expressions of c-erbB-2 and p53 in squamous cell carcinoma and CIN were statistically significant (P &gt;0.05). The differential expressions of Bcl-2, c-erbB-2, and p53 in CIN 3 were statistically significant in comparison to CIN 1 and CIN 2 (P &lt;0.05). Conclusion Overexpression of Bcl-2 occurs early in the development of cervical cancer, whereas p16 and c-erbB-2 overexpression are markers for cell malignancy. The expression of p53 is correlated with the development of cervical cancer.

Screening of Cervical Cancer by VIA among women in Rajshahi Medical College Hospital

Introduction: Visual inspection of cervix after application of 3-5% acetic acid (VIA) is a potential alternative to Pap smear cytology for screening of cervical cancer in resource poor settings. VIA has gained popularity and proven itself in many clinical trials as an adequate screening test. VIA is an attractive alternative to Pap smears for its ease of use, low-cost and fewer physician visits. Currently VIA is done in tertiary level hospitals by trained health care providers to generalize its efficacy.Objective: The main objective of this study was to evaluate the efficacy of visual inspection based screening approach in the detection of precancerous &amp; early cancerous lesions of the cervix.Materials and Methods: This study was done as a part of an ongoing screening program in Rajshahi Medical College Hospital from July 2008 to December 2009. VIA was carried out in 540 eligible women attending Gynae OPD for gynecological problems. The women underwent a complete clinical evaluation. Detection of well-defined, opaque, acetowhite lesion close to squamocolumnar junction (SCJ) or in transitional zone (TZ), well-defined circumferential, acetowhite lesions or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA. All screened women evaluated by colposcopy and biopsy were taken from colposcopically suspected areas or in cases of VIA negative from different quadrants of the cervix. The final diagnosis was based on histology, which allowed direct estimation of sensitivity, specificity, and predictive values of VIA. Those with CIN I or cancerous lesions diagnosed by histology were considered as true positive.Results: Out of 540 patients screened, 328(61%) were VIA negative and 212(39%) were VIA positive. Out of positive cases 87 (41%)%) seemed to have pathology. Colposcopy yielded normal results in 340 (63%) cases, low grade CIN in 138 (26%) cases, high grade CIN in 44 (8%) cases and cancer in 18 (3%) cases making total 200 cases. Of the 200 (37%) patients with positive colposcopy, 98 (49%) turned out to be negative on histology. There were biopsy proven chronic cervicitis and metaplastic changes in 423 (78%) cases, CIN I in 66 (12%) cases, CIN II in 25 (5%) cases, CIN III/ carcinoma-in-situ in 5 (1%) cases. Eighteen (3%) cases of cervical carcinoma were diagnosed on colposcopy but ultimately 21(21%) cases of invasive cancer were detected on histology. The sensitivity of VIA for biopsy proven CIN I was 74.36%, specificity 75.8%, positive predictive value 41.04%, &amp; negative predictive value 90.85%.Conclusion: VIA can differentiate a normal cervix from a precancerous cervix with reasonable accuracy. Till now a good number of studies had been carried out in different countries of the world and now it is well established that the sensitivity of VIA equaled or exceeded the reported rates for conventional cervical cytology. As it is low cost and simple method, it can be set in any hospital or any health care centre of rural or urban areas of poor resource settings.Bangladesh J Obstet Gynaecol, 2013; Vol. 28(1) : 31-37

Rare Case of Painless Jaundice

Cervical cancer remains a major cause of morbidity and mortality. The vast majority are related to human papillomavirus infection which is ubiquitous in the population and results in approximately 12,710 new cases and 4,290 deaths in the US annually, making it the third most common gynecological cancer diagnosis and cause of death. Squamous cell carcinoma and adenocarcinoma account for approximately 69% and 25% of cases of cervical carcinoma, respectively. Cervical cancer may spread to adjacent organs via direct extension or to distant sites through lymphatic or hematogenous dissemination. The most common sites of hematogenous spread are the lung, liver, and bone. Here we present a case of cervical cancer with metastasis to the biliary system without liver metastasis causing common bile duct obstruction with jaundice. A 63-year-old woman with history of cervical cancer presented with painless jaundice. She was diagnosed four months prior with stage IV-A cervical carcinoma and underwent chemotherapy with cisplatin and whole pelvic radiation. After completing five courses of brachytherapy, the last of which was one month prior to admission, she was determined to be in clinical remission. Upon admission, MRCP was obtained and demonstrated evidence of biliary obstruction. ERCP then showed high-grade stenosis of the proximal CBD and beading of the intrahepatic bile ducts, which was treated with stenting. ERCP brushings confirmed metastatic disease with atypical epithelial cells consistent with metastatic SCC. Immunohistochemical studies demonstrated strong and diffuse cytoplasmic and nuclear p16 staining while MIB-1 staining was present in 40-50% of the neoplastic cells. Metastatic cervical carcinoma is a devastating disease with a grim prognosis. Although the cancer typically spreads by direct extension, distant metastases to the lung, liver, and bone have been described. Per our literature review, there has been a single case of metastasis to the ampulla of Vater but none to the bile ducts itself. This patient with a history of stage IV-A cervical carcinoma presented with painless jaundice and was subsequently diagnosed with bile duct metastasis. Unfortunately, the patient was not a candidate for surgical or chemotherapy treatment and was sent to hospice due to her functional status. Fortunately, the incidence and mortality rate of cervical cancer has declined in recent years in the US due to increased cervical cancer screening vigilance.Figure 1Figure 2Figure 3

Rare subtype(s) and frequency of multi-viral subtype high-risk human papilloma virus infection in high-grade squamous intraepithelial lesion and squamous cell carcinoma in a cervical carcinoma prevalent developing country: a multiplex real-time polymerase chain reaction-based pilot study.

BackgroundBangladesh, with a population of 160 million and nearly half being women, has the 4th highest rate of cervical carcinoma deaths in the world. It is projected that ∼500,000 of these women would die of this entirely preventable cancer by 2030. HPV vaccination is not widely offered in Bangladesh. This pilot study is designed to find out the prevalence of rare and multi-viral high-risk HPV (hrHPV) subtype(s) infection which may help strategize a large scale vaccination program in tackling cervical carcinoma in the country.MethodsForty cases of cervical High-Grade squamous intraepithelial lesion (HSIL) and Squamous cell carcinoma (SqCa) were collected. DNA was extracted from tissue representing HSIL and SqCa and multiplex PCR was run to identify all 15 hrHPV subtypes along with known positive controls.ResultsOf the total, 27 cases were biopsies/cones and 13 were hysterectomies including 5 HSIL and 35 SqCa. Infection caused by rare subtypes, hrHPV 45 and 52, were found in only two cases. Multi-subtype infection, detected in 28 % cases, was limited to HPV16/18 in all cases but one; one case showed hrHPV16/52 combination.ConclusionA remarkable homogeneity of hrHPV 16 infection is noted in women with HSIL & SqCa in this country in these limited samples. This finding is in sharp contrast to the reports from western countries of frequent multi-viral and rare subtype hrHPV infection. This pilot study suggests that a vaccination program may be highly effective in controlling cervical cancer there. A larger study, however, is required to ratify the findings.

Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates proliferation, invasion and chemoresistance, and regulates Src and Akt signaling.

Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number of types of human cancer. However, its involvement in human cervical carcinoma remains unclear. The present study aimed to explore the clinical significance and biological characteristics of CrkL in human cervical carcinoma. CrkL protein expression was examined in tissue samples from 92 cases of cervical carcinoma using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92 cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines and its effects on biological behavior were examined. CrkL overexpression was revealed to promote cell proliferation, invasion and chemoresistance. In addition, CrkL overexpression increased the level of Src and Akt phosphorylation. Treatment with the Src inhibitor dasatinib eliminated the effect of CrkL on cell invasion. In conclusion, the current results demonstrate that CrkL is an oncoprotein overexpressed in cervical carcinoma which contributes to malignant cell growth and chemoresistance. In addition, the findings indicate that CrkL promotes cervical cancer cell invasion through a Src-dependent pathway.