Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell carcinoma by inhibiting Wnt/β-catenin signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Hui; Jiao, Shun; Li, Xin

Aberrant activation of the Wnt/β-catenin signaling pathway is common in human cervical cancers and has great potential therapeutic value. We show that tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell carcinoma through inhibiting Wnt/β-catenin signaling pathway. Tigecycline is effective in inducing apoptosis, inhibiting proliferation and anchorage-independent colony formation of Hela cells. The inhibitory effects of tigecycline are further enhanced upon combination with paclitaxel, a most commonly used chemotherapeutic drug for cervical cancer. In a cervical xenograft model, tigecycline inhibits tumor growth as a single agent and its combination with paclitaxel significantly inhibits more tumor growth throughout the duration ofmore » treatment. We further show that tigecycline decreases level of both cytoplasmic and nuclear β-catenin and suppressed Wnt/β-catenin-mediated transcription through increasing levels of Axin 1 in Hela cells. In addition, stabilization or overexpression of β-catenin using pharmacological and genetic approaches abolished the effects of tigecycline in inhibiting proliferation and inducing apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition to the treatment armamentarium for cervical cancer and targeting Wnt/β-catenin represents a potential therapeutic strategy in cervical cancer. - Highlights: • We repurposed the antibiotic drug tigecycline for cervical cancer treatment. • Tigecycline is effectively against cervical cancer cells in vitro and in vivo. • Combination of tigecycline and paclitaxel is synergistic in targeting Hela cells. • Tigecycline acts on Hela cells through inhibiting Wnt/β-catenin signaling.« less

Enlarged squamous cell nuclei in cervical cytologic specimens from perimenopausal women ("PM Cells") : a cause of ASC overdiagnosis.

PubMed

Cibas, Edmund S; Browne, Tara-Jane; Bassichis, Michelle H Mantel; Lee, Kenneth R

2005-07-01

We studied the appropriateness of interpreting squamous cells with enlarged, smooth, bland nuclei in perimenopausal women ("PM cells") as atypical squamous cells (ASCs). Papanicolaou smears (Paps) from 100 women (40-55 years old) with a cytologic interpretation of ASC of undetermined significance (ASCUS) and human papillomavirus (HPV) testing or a biopsy within 6 months were reviewed by 2 observers without knowledge of the biopsy diagnosis or HPV results. Cases in which both reviewers agreed that the Paps were diagnosed more properly as "negative for intraepithelial lesion or malignancy" were compared with cases of "true ASCUS," using histologic squamous intraepithelial lesion and/or a positive high-risk HPV test as a positive outcome (abnormal follow-up). Of 100 cases, 28 were reclassified as benign by both observers. In 15 of these, the original ASCUS interpretation was based on cells with bland nuclear enlargement (2-3 times the area of intermediate cell nuclei), smooth nuclear membranes, and fine chromatin. Abnormal follow-up was identified in 1 (7%) of 15 benign cases but in 30 (42%) of 72 true ASCUS cases (P = .023). PM cells are a significant cause of ASC overdiagnosis in women 40 to 55 years old. Cervical Paps with cells no more atypical than these can be interpreted safely as negative for intraepithelial lesion or malignancy.

DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer.

PubMed

Kim, Mi-Kyung; Lee, In-Ho; Lee, Ki-Heon; Lee, Yoo Kyung; So, Kyeong A; Hong, Sung Ran; Hwang, Chang-Sun; Kee, Mee-Kyung; Rhee, Jee Eun; Kang, Chun; Hur, Soo Young; Park, Jong Sup; Kim, Tae-Jin

2016-03-01

DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.

Screening frequency and atypical cells and the prediction of cervical cancer risk.

PubMed

Chen, Yun-Yuan; You, San-Lin; Koong, Shin-Lan; Liu, Jessica; Chen, Chi-An; Chen, Chien-Jen

2014-05-01

To evaluate the screening efficacy and importance of atypical squamous cells and atypical glandular cells in predicting subsequent cervical cancer risk. This national cohort study in Taiwan analyzed associations between Pap test screening frequency and findings in 1995-2000 and subsequent risk of squamous cell carcinoma and adenocarcinoma after 2002. Women aged 30 years or older in 1995 without a cervical cancer history were included. Multivariate-adjusted hazard ratios and their 95% confidence intervals (CIs) were assessed using Cox regression analysis. During a total follow-up of 31,693,980 person-years in 2002-2008, 9,471 squamous cell carcinoma and 1,455 adenocarcinoma cases were newly diagnosed, resulting in 2,067 deaths. The risk of developing and dying from squamous cell carcinoma decreased significantly with increasing attendance frequency between 1995 and 2000 (all P values for trend<.001). Women who attended more than three screenings in 1995-2000 had 0.69-fold and 0.35-fold decrease in incidence and mortality of adenocarcinoma, respectively, compared with women who never attended any screenings. Abnormal cytologic findings were significant predictors of the incidence and mortality of cervical cancers. The adjusted hazard ratio (95% CI) of developing squamous cell carcinoma was 29.94 (22.83-39.25) for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions, and the adjusted hazard ratio (95% CI) of developing adenocarcinoma was 49.43 (36.49-66.97) for atypical glandular cells. Significant reductions in cervical adenocarcinoma occurred in women who attend three or more annual screenings in 6 years. High-grade atypical squamous cells and atypical glandular cells are important predictors of subsequent adenocarcinoma and squamous cell carcinoma. II.

TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

PubMed

Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

2016-06-01

Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.

Progression of abnormal MIB-1 staining patterns of reserve cells in cervical smears from women ultimately developing high grade squamous intraepithelial lesions.

PubMed

Siemens, Frederike C; van Haaften, Carolien; Kuijpers, Johan C; Helmerhorst, Theo J M; Boon, Mathilde E

2006-01-01

To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens. Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size. The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.

Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

PubMed

Xu, Dianbo; Wang, Danbo; Wang, Shuo; Tian, Ye; Long, Zaiqiu; Ren, Xuemei

2017-11-01

The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P < 0.001), lymphovascular invasion (P = 0.001), LNM (P < 0.001), and greater than one half stromal infiltration (P < 0.001). Multivariate analysis identified LNM (P < 0.001, odds ratio [OR] = 4.399), tumor diameter of greater than >4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients

Does cervical lymph node recurrence after oesophagectomy or definitive chemoradiotherapy for thoracic oesophageal squamous cell carcinoma benefit from salvage treatment?

PubMed

Yuan, Xiaoli; Lv, Jiahua; Dong, Hang; Wang, Jiuhui

2017-05-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does cervical lymph node recurrence after oesophagectomy or definitive chemoradiotherapy for thoracic oesophageal squamous cell carcinoma benefit from salvage treatment?' Altogether, 659 articles were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these articles were tabulated. All were retrospective or institutional reports. Seven of the 8 articles suggested that cervical lymphadenectomy (LD) or multimodal treatment with LD and radiotherapy (RT)/chemoradiotherapy (CRT) was associated with good outcomes in patients with cervical lymph node (LN) recurrence after curative oesophagectomy for thoracic oesophageal squamous cell carcinoma (ESCC). Salvage cervical LD was the main treatment and could achieve locoregional disease control and prolonged survival. It was safe with no postoperative mortality, although minor LD complications such as recurrent laryngeal nerve palsy were observed. Most reports highlighted that a solitary cervical LN relapse after curative oesophagectomy could be considered a good prognostic indicator for salvage cervical LD or multimodal treatment. Patients with microscopic residual tumour after salvage cervical LD or suspected extensive metastasis might benefit from a combination of LD and CRT. One article described salvage RT alone, again with a positive effect on survival. Conversely, data suggested that salvage LD in patients after definitive CRT for thoracic ESCC was not likely to control locoregional disease. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

DNA methylation in human papillomavirus-infected cervical cells is elevated in high-grade squamous intraepithelial lesions and cancer

PubMed Central

Lee, Ki-Heon; So, Kyeong A; Hong, Sung Ran; Hwang, Chang-Sun; Kee, Mee-Kyung; Rhee, Jee Eun; Kang, Chun; Hur, Soo Young; Park, Jong Sup

2016-01-01

Objective DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. Methods A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. Results Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). Conclusion DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies. PMID:26768780

A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes.

PubMed

Ali, Arif N; Switchenko, Jeffrey M; Kim, Sungjin; Kowalski, Jeanne; El-Deiry, Mark W; Beitler, Jonathan J

2014-11-15

The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes ("unknown primaries"). The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for patients with an H&N tumor site who were diagnosed between 2004 and 2011. The SEER patients were identified according to their H&N primary tumor site and clinically positive cervical lymph node levels at the time of presentation. The SEER patient data set was randomly divided into 2 data sets for the purposes of internal split-sample validation. The effects of cervical lymph node levels, age, race, and sex on H&N primary tumor site were examined using univariate and multivariate analyses. Multivariate logistic regression models and an associated set of nomograms were developed based on relevant factors to provide probabilities of tumor site origin. Analysis of the SEER database identified 20,011 patients with H&N disease with both site-level and lymph node-level data. Sex, race, age, and lymph node levels were associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and larynx) in the multivariate models. Internal validation techniques affirmed the accuracy of these models on separate data. The incorporation of epidemiologic and lymph node data into a predictive model has the potential to provide valuable guidance to clinicians in the treatment of patients with squamous cell carcinoma confined to the cervical lymph nodes. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Expressions of EphA2 and EphrinA-1 in early squamous cell cervical carcinomas and their relation to prognosis

PubMed Central

Holm, Ruth; de Putte, Gregg Van; Suo, Zhenhe; Lie, A Kathrine; Kristensen, Gunnar B

2008-01-01

By using immunohistochemistry we investigated the expression of EphA2 and EphrinA-1 in 217 early squamous cell cervical carcinomas and examine their prognostic relevance. For EphA2 expression, 21 tumors (10%) showed negative, 108 (50%) weak positive, 69 (32%) moderate positive and 19 (9%) strong positive, whereas for EphrinA-1 expression, 33 tumors (15%) showed negative, 91 (42%) weak positive, 67 (31%) moderate positive and 26 (12%) strong positive. In univariate analysis high expression (strong staining) of EphrinA-1 was associated with poor disease-free (P = 0.033) and disease-specific (P = 0.039) survival. However, in the multivariate analyses neither EphrinA-1 nor EphA2 was significantly associated to survival. The increased levels of EphA2 and EphrinA-1 in a relative high number of early stage squamous cell carcinomas suggested that these two proteins may play an important role in the development of a subset of early cervical cancers. However, EphA2 and EphrinA-1 were not independently associated with clinical outcome. PMID:18566674

Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

PubMed

Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

2015-08-01

To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis.

PubMed

Chen, Mei; Zhang, Yuan; Zheng, Peng-Sheng

2017-01-01

Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis.

Tafazzin (TAZ) promotes the tumorigenicity of cervical cancer cells and inhibits apoptosis

PubMed Central

Chen, Mei; Zhang, Yuan; Zheng, Peng-Sheng

2017-01-01

Tafazzin (TAZ) is often aberrantly expressed in some cancers, including rectal cancer and thyroid neoplasms. However, the function of TAZ in cervical cancer cells remains unknown. This study aims to explore the expression and function of TAZ in cervical cancer cells. Here, we determined the expression of TAZ protein in normal cervical tissue (NC, n = 27), high-grade squamous intraepithelial lesions (HSIL, n = 26) and squamous cervical carcinoma (SCC, n = 41) by immunohistochemistry, the expression of TAZ protein gradually increased from NC to HSIL to SCC. TAZ was overexpressed or down-regulated in cervical cancer cells by stably transfecting a TAZ-expressing plasmid or a shRNA plasmid targeting TAZ. In vitro, the cell growth curves and MTT assays showed that TAZ may promote the growth and viability of cervical cancer cells. In vivo, xenografts experiment showed that TAZ may increase tumor-forming ability. The percentage of apoptosis cells analyzed by FACS and TUNEL assays consistently showed that TAZ inhibits apoptosis in cervical cancer cells. Furthermore, the Cleaved Caspase 9 and Cleaved Caspase 3 were down-regulated by TAZ in cervical cancer cells. Taken together, this study demonstrated that TAZ is overexpressed in cervical cancer and may promote tumorigenicity of cervical cancer cells and inhibit apoptosis. PMID:28489874

Which Patients With Cervical Squamous Cell Carcinoma Might Benefit From Neoadjuvant Chemotherapy?

PubMed

Mahmoud, Omar; Einstein, Mark H

2018-06-01

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 55-year-old postmenopausal woman, gravida 5 para 5, with past medical history significant for hypertension, presented to the emergency department with profuse vaginal bleeding and a hemoglobin level of 9 g/dL. The biopsy from an irregular 6-cm cervical mass was consistent with moderately differentiated cervical squamous cell carcinoma. The physical examination did not reveal vaginal or parametrial extension of the tumor. Pelvic magnetic resonance imaging disclosed the known carcinoma, as well as a 9.2 × 7.7 × 6.7 cm anterior uterine fibroid (Fig 1). A staging positron emission tomography scan was negative for metastatic disease. After blood transfusion and vaginal packing, the patient was referred to discuss the immediate management of her newly diagnosed bleeding bulky cervical cancer. In the absence of parametrial or vaginal extension and in the absence of lymph node metastasis (both on clinical examination and imaging), she was classified as having International Federation of Gynecology and Obstetrics stage IB2 disease.

High growth fraction at 9 grays of radiotherapy is associated with a good prognosis for patients with cervical squamous cell carcinoma.

PubMed

Oka, K; Suzuki, Y; Nakano, T

2000-10-01

MIB-1, a murine monoclonal antibody, recognizes the Ki-67 antigen of routinely processed paraffin sections after microwave treatment. Cycling cells are positive for MIB-1 in their nucleus, and quiescent cells are negative for MIB-1. The MIB-1 labeling index represents the growth fraction of the cell population. A total of 150 cervical biopsy specimens were taken from 75 consecutive patients with cervical squamous cell carcinomas before radiotherapy (RT) and at 9 grays (Gy) of RT and were investigated to analyze the correlation between the MIB-1 labeling index or the deltaMIB-1 labeling index and patient prognosis or local disease control. The deltaMIB-1 index was calculated as the MIB-1 index at 9 Gy minus the MIB-1 index before RT. The mean MIB-1 index was 38% (range, 11-67%) before RT and 54% (range, 15-85%) at 9 Gy. The MIB-1 index at 9 Gy was related to prognosis, including overall survival (P = 0.025), disease free survival (P = 0. 024), and metastasis free survival (P = 0.045). Patients who had a deltaMIB-1 index > 20% showed a trend toward a higher disease free survival rate compared with patients who had a deltaMIB-1 index < 20% (P = 0.093). Neither the MIB-1 index nor the deltaMIB-1 index was associated with local disease control. The high growth fraction at 9 Gy is regarded as a predictive factor for a good prognosis in patients with cervical squamous cell carcinoma patients who undergo RT alone.

Phase Ib Study of BKM120 With Cisplatin and XRT in High Risk Locally Advanced Squamous Cell Cancer of Head and Neck

ClinicalTrials.gov

2017-05-19

Carcinoma, Squamous Cell of Head and Neck; HPV Positive Oropharyngeal Squamous Cell Carcinoma; Hypopharyngeal Cancer; Early Invasive Cervical Squamous Cell Carcinoma; Carcinoma of Larynx; Cancer of Nasopharynx

Breast and splenic metastases of squamous cell carcinoma from the uterine cervix: a case report.

PubMed

Aitelhaj, Meryem; Khoyaali, Siham L; Boukir, Anouar; Elkabous, Mustapha; Abahssain, Halima; Mrabti, Hind; El Khannoussi, Basma; Errihani, Hassan

2014-11-04

Metastases to the breast from extramammary malignancies are infrequent, the most common primary sites are malignant melanoma, leukemia, lymphoma, and cancer of the lung, stomach, prostate and ovary. The cervical origin is exceptional. Splenic metastasis from squamous cell carcinoma of the cervix is also rare. To the best of our knowledge, only three cases of isolated splenic metastasis have been reported in the literature. We describe the case of a 55-year-old North African woman who presented with a nodule in her left breast eight months after treatment for stage IIB squamous cell uterine cervical carcinoma. The excisional biopsy with histological study demonstrated a poorly differentiated squamous cell carcinoma. A computed tomography scan revealed a splenic secondary location. We report here a case of two unusual metastatic sites of uterine cervical carcinoma, the breast and spleen. It is the first case of this association without widespread disease.

A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

PubMed

Alvarez, Edwin A; Wolfson, Aaron H; Pearson, J Matt; Crisp, Meredith P; Mendez, Luis E; Lambrou, Nicholas C; Lucci, Joseph A

2009-05-01

This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Breast and splenic metastases of squamous cell carcinoma from the uterine cervix: a case report

PubMed Central

2014-01-01

Introduction Metastases to the breast from extramammary malignancies are infrequent, the most common primary sites are malignant melanoma, leukemia, lymphoma, and cancer of the lung, stomach, prostate and ovary. The cervical origin is exceptional. Splenic metastasis from squamous cell carcinoma of the cervix is also rare. To the best of our knowledge, only three cases of isolated splenic metastasis have been reported in the literature. Case presentation We describe the case of a 55-year-old North African woman who presented with a nodule in her left breast eight months after treatment for stage IIB squamous cell uterine cervical carcinoma. The excisional biopsy with histological study demonstrated a poorly differentiated squamous cell carcinoma. A computed tomography scan revealed a splenic secondary location. Conclusions We report here a case of two unusual metastatic sites of uterine cervical carcinoma, the breast and spleen. It is the first case of this association without widespread disease. PMID:25366471

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

PubMed

Vlahos, N P; Dragisic, K G; Wallach, E E; Burroughs, F H; Fluck, S; Rosenthal, D L

2000-04-01

This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women 35 years old (17.8% vs 6.3%; P =.0378). Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma.

PubMed

Kong, Fei; Li, Yunguang; Hu, Enze; Wang, Rui; Wang, Junhao; Liu, Jin; Zhang, Jinsan; He, Dacheng; Xiao, Xueyuan

2016-01-01

S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.

Association of cystic neck metastases and human papillomavirus-positive oropharyngeal squamous cell carcinoma.

PubMed

McHugh, Jonathan B

2009-11-01

Human papillomavirus is an established cause of oropharyngeal squamous cell carcinoma. Similar to cervical cancer, these cancers are usually caused by high-risk human papillomavirus types 16 and 18 and are associated with high-risk sexual behaviors. Human papillomavirus-associated oropharyngeal squamous cell carcinoma typically affects the palatine and lingual tonsils and frequently results in cystic neck metastases. The histopathology of this subset of head and neck squamous cell carcinoma is unique and typically characterized by poorly differentiated, nonkeratinizing morphology with a basaloid appearance. These tumors occur in younger patients and are more often seen in nonsmokers compared with conventional oral cavity and oropharyngeal squamous cell carcinomas. The incidence of human papillomavirus-associated squamous cell carcinoma is increasing. Recognition of this unique clinicopathologic subset of head and neck carcinoma is important because these patients typically respond more favorably to organ-sparing treatment modalities and have an improved prognosis.

Optoelectronic method for detection of cervical intraepithelial neoplasia and cervical cancer

NASA Astrophysics Data System (ADS)

Pruski, D.; Przybylski, M.; Kędzia, W.; Kędzia, H.; Jagielska-Pruska, J.; Spaczyński, M.

2011-12-01

The optoelectronic method is one of the most promising concepts of biophysical program of the diagnostics of CIN and cervical cancer. Objectives of the work are evaluation of sensitivity and specificity of the optoelectronic method in the detection of CIN and cervical cancer. The paper shows correlation between the pNOR number and sensitivity/specificity of the optoelectronic method. The study included 293 patients with abnormal cervical cytology result and the following examinations: examination with the use of the optoelectronic method — Truscreen, colposcopic examination, and histopathologic biopsy. Specificity of the optoelectronic method for LGSIL was estimated at 65.70%, for HGSIL and squamous cell carcinoma of cervix amounted to 90.38%. Specificity of the optoelectronic method used to confirm lack of cervical pathology was estimated at 78.89%. The field under the ROC curve for the optoelectronic method was estimated at 0.88 (95% CI, 0.84-0.92) which shows high diagnostic value of the test in the detection of HGSIL and squamous cell carcinoma. The optoelectronic method is characterised by high usefulness in the detection of CIN, present in the squamous epithelium and squamous cell carcinoma of cervix.

Cervical nodal metastases in squamous cell carcinoma of the head and neck: what to expect.

PubMed

Mukherji, S K; Armao, D; Joshi, V M

2001-11-01

The treatment and management of malignancies of the head and neck is directly altered by the presence of metastatic cervical adenopathy. The treatment of nodal metastases in squamous cell carcinoma of the head and neck (HNSCCA) is determined by the lymphatic drainage of the upper aerodigestive tract. The lymphatic drainage is site-specific and occurs in a predictable manner. The purpose of this text is to provide an overview of the normal routes of lymphatic drainage in the head and neck and correlate this with the current nodal classification system. The specific aims of this manuscript are to 1) illustrate the expected lymphatic drainage patterns of HNSCCA arising in the different subsites (nasopharynx, oropharynx, oral cavity, larynx, and hypopharynx) and 2) review the expected frequency of metastases within nodal groups for HNSCCA that arise in these locations. An understanding of the topographical distribution and incidence of cervical lymph node metastases plays an integral role in the physical examination and radiological evaluation of patients with HNSCCA. For the neuroradiologist, this information may increases the ability to identify those nodal groups at risk for metastatic involvement. Copyright 2001 John Wiley & Sons, Inc. Head Neck 23: 995-1005, 2001.

Synchronous metastatic adenoid cystic and squamous cell carcinoma of the cervical lymph nodes 31 years after ablation of the primary palatal tumour.

PubMed

Doumas, Stergios; Barrett, Andrew W; Carrillo, Mauricio; Tighe, John V

2013-10-01

The coexistence of different types of malignancy in cervical lymph nodes has been reported previously. We report the first case, to the best of our knowledge, of concurrent metastatic adenoid cystic carcinoma and squamous cell carcinoma (SCC) in cervical lymph nodes. A primary SCC developed three decades after treatment for adenoid cystic carcinoma of the palate, and the synchronous metastases became clinically apparent the following year. The aetiology of the SCC may have been related to radiotherapy or smoking. Whether the adenoid cystic carcinoma would have remained dormant, or was reactivated after perturbation of host defence mechanisms, is not known. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

PubMed

Balacescu, Ovidiu; Balacescu, Loredana; Tudoran, Oana; Todor, Nicolae; Rus, Meda; Buiga, Rares; Susman, Sergiu; Fetica, Bogdan; Pop, Laura; Maja, Laura; Visan, Simona; Ordeanu, Claudia; Berindan-Neagoe, Ioana; Nagy, Viorica

2014-04-08

Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the

Clinical implication of elevated human cervical cancer oncogene-1 expression in esophageal squamous cell carcinoma.

PubMed

Liu, Ying; Li, Ke; Ren, Zhonghai; Li, Shenglei; Zhang, Hongyan; Fan, Qingxia

2012-07-01

The human cervical cancer oncogene 1 (HCCR-1), a novel human oncoprotein, has been shown to be upregulated in various human tumors and plays a critical role in tumorigenesis and tumor progression. Here, the authors investigated HCCR-1 level in esophageal squamous cell carcinoma (ESCC) tissues and assessed the correlation between HCCR-1 level and prognosis of the patients with ESCC. HCCR-1 levels were investigated by immunohistochemistry, in situ hybridization, real-time quantitative RT-PCR and Western blotting methods; Kaplan-Meier curve was used to evaluate the prognostic value of HCCR-1 level in patients with ESCC using log-rank test. HCCR-1 displayed high levels in ESCC tissues compared to squamous dysplasia tissues and normal esophageal epithelial tissues. No significant correlation was observed between the levels of HCCR-1 mRNA and protein and gender and age (all p>0.05) but obviously related to histological grade, clinical stage, and lymph node metastasis (all p<0.001). Moreover, the survival rate of the patients with low HCCR-1 levels was higher than that of the patients with high HCCR-1 levels (both p<0.05). These data demonstrate that HCCR-1 may be used as a novel predictor for the prognosis of the patients with ESCC.

Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells

PubMed Central

Smith, Stephen P.; Scarpini, Cinzia G.; Groves, Ian J.; Odle, Richard I.; Coleman, Nicholas

2016-01-01

Development of cervical squamous cell carcinoma requires increased expression of the major high-risk human-papillomavirus (HPV) oncogenes E6 and E7 in basal cervical epithelial cells. We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of ‘master regulators’ for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n = 7) or HPV16 E7 (n = 5). We validated our data by depleting E6/E7 in relevant cells and by functional analysis of selected genes in vitro. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins. PMID:27457222

Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

PubMed

Khot, Komal P; Deshmane, Swati; Choudhari, Sheetal

2016-03-01

Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management.

Radiological detection of extracapsular spread in head and neck squamous cell carcinoma (HNSCC) cervical metastases.

PubMed

Url, C; Schartinger, V H; Riechelmann, H; Glückert, R; Maier, H; Trumpp, M; Widmann, G

2013-10-01

Extracapsular spread of cervical lymph nodes deteriorates the prognosis of patients with head and neck squamous cell carcinoma. Postoperative radiochemotherapy is superior to postoperative radiotherapy alone in patients with histologically proven extracapsular spread. If extracapsular spread can be detected preoperatively, patients may favor primary radiochemotherapy instead of primary surgery plus postoperative radiochemotherapy. Computed tomography (CT) scans of nodal positive head and neck squamous cell carcinoma patients treated between 2008 and 2010 with comprehensive neck dissection as part of first line surgical treatment were retrospectively scanned for extracapsular spread by two blinded radiologists. If a positive lymph node was identified by the pathologist, CT scans were assessed for extracapsular spread retrospectively. CT criteria for Extracapsular spread were apparent fat and soft tissue infiltration or infiltration of sternocleidomastoid muscle, internal jugular vein or carotid artery. Radiologic judgment was compared with histological evidence of extracapsular spread and specificity and sensitivity of CT detection was calculated. Forty-nine patients with histologically proven positive lymph nodes (pN+) were included. Extracapsular spread was histologically proven in 17 cases; the number of all affected lymph nodes was not listed. Radiologist 1 found extracapsular spread in CT scans of 15/49 patients and radiologist 2 in 16/49 patients (Cohen's kappa=0.86; p<0.01). Sensitivity of radiologic extracapsular spread detection was 73% (95% confidential index (CI): 44.0-89.7%) and specificity 91% (75.0-98.0%). Extracapsular spread depicted on computed tomography using strict criteria has high specificity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

FDG and FMISO PET Hypoxia Evaluation in Cervical Cancer

ClinicalTrials.gov

2016-12-28

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

A retrospective analysis of preoperative staging modalities for oral squamous cell carcinoma.

PubMed

Kähling, Ch; Langguth, T; Roller, F; Kroll, T; Krombach, G; Knitschke, M; Streckbein, Ph; Howaldt, H P; Wilbrand, J-F

2016-12-01

An accurate preoperative assessment of cervical lymph node status is a prerequisite for individually tailored cancer therapies in patients with oral squamous cell carcinoma. The detection of malignant spread and its treatment crucially influence the prognosis. The aim of the present study was to analyze the different staging modalities used among patients with a diagnosis of primary oral squamous cell carcinoma between 2008 and 2015. An analysis of preoperative staging findings, collected by clinical palpation, ultrasound, and computed tomography (CT), was performed. The results obtained were compared with the results of the final histopathological findings of the neck dissection specimens. A statistical analysis using McNemar's test was performed. The sensitivity of CT for the detection of malignant cervical tumor spread was 74.5%. The ultrasound obtained a sensitivity of 60.8%. Both CT and ultrasound demonstrated significantly enhanced sensitivity compared to the clinical palpation with a sensitivity of 37.1%. No significant difference was observed between CT and ultrasound. A combination of different staging modalities increased the sensitivity significantly compared with ultrasound staging alone. No significant difference in sensitivity was found between the combined use of different staging modalities and CT staging alone. The highest sensitivity, of 80.0%, was obtained by a combination of all three staging modalities: clinical palpation, ultrasound and CT. The present study indicates that CT has an essential role in the preoperative staging of patients with oral squamous cell carcinoma. Its use not only significantly increases the sensitivity of cervical lymph node metastasis detection but also offers a preoperative assessment of local tumor spread and resection borders. An additional non-invasive cervical lymph node examination increases the sensitivity of the tumor staging process and reduces the risk of occult metastasis. Copyright © 2016 European

Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

PubMed

Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

2014-02-01

Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value <0.05 was considered statistically significant. 196 patients with SCC of the oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis.

PubMed

Kou, Yurong; Zhao, Tengfei; Huang, Shaohui; Liu, Jie; Duan, Weiyi; Wang, Yunjing; Wang, Zechen; Li, Delong; Ning, Chunliu; Sun, Changfu

2017-01-01

The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis. Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure) without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3. Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0-7.0). Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0-10.0). Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels. Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated level IIb, level IIb dissection could be avoided when the primary lesions were in early stages (T1 and T2), with the exception of tongue cancer. It is recommended to dissect level IIb tongue cancers without considering the stages of primary lesions and the lymph nodes status. It is also suggested that level IIb dissection should be performed in patients preoperatively or intraoperatively found with multilevel neck metastasis, especially level IIa metastasis.

Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

PubMed

Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

2012-12-01

In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

Revised Terminology for Cervical Histopathology and Its Implications for Management of High-Grade Squamous Intraepithelial Lesions of the Cervix

PubMed Central

Waxman, Alan G.; Chelmow, David; Darragh, Teresa M.; Lawson, Herschel; Moscicki, Anna-Barbara

2014-01-01

In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is “low-grade” or “high-grade squamous intraepithelial lesion (SIL).” This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using “intraepithelial neoplasia” (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology. PMID:23168774

Prevalence and impact on clinicopathological characteristics of human papillomavirus-16 DNA in cervical lymph node metastases of head and neck squamous cell carcinoma.

PubMed

Weiss, Daniel; Koopmann, Mario; Rudack, Claudia

2011-06-01

Human papillomavirus (HPV) is a basic risk factor for head and neck squamous cell carcinoma (HNSCC). Little knowledge exists about the impact of HPV on clinical diagnostic and therapy of patients with HNSCC. We evaluated the evidence of HPV16 in 131 retrospectively collected HNSCC and associated cervical lymph node metastases by HPV16 real-time polymerase chain reaction (PCR) and p16 immunohistochemistry and its impact on clinicopathological characteristics. HPV16-DNA and p16 overexpression were present in 27% of HNSCCs. All cervical lymph node metastases of HPV16-positive HNSCC showed HPV16-DNA. HPV16 was strongly associated with tumors arising from the oropharyngeal site (p < .000001), favorable outcome after standard therapy in univariate (p = .001) and multivariate (p = .0004) analysis, and cervical lymph node metastases before primary detection. HPV16-diagnostic in cervical lymph node metastases can predict the site of tumor origin in case of carcinoma of unknown primary (CUP) and favorable outcome and should, therefore, be included in routine diagnostic workup. Copyright © 2010 Wiley Periodicals, Inc.

p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

PubMed

Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

2012-11-01

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

Increased expression of the retinoic acid-metabolizing enzyme CYP26A1 during the progression of cervical squamous neoplasia and head and neck cancer.

PubMed

Osanai, Makoto; Lee, Gang-Hong

2014-10-07

Retinoic acid (RA) is a critical regulator of cell differentiation, proliferation, and apoptosis in various cell types. Recently, the RA-metabolizing enzyme CYP26A1 (cytochrome P450, family 26, subfamily A, polypeptide 1) has been shown to have an oncogenic function in breast carcinogenesis. However, the relevance of elevated CYP26A1 expression in human cancers remains to be clarified. We immunohistochemically examined the expression of CYP26A1 in cervical squamous cell carcinoma (SCC) and its precursors, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as head and neck cancer (HNC). The association between CYP26A1 expression and a number of clinicopathological parameters was also evaluated. CYP26A1 was not expressed in normal cervical epithelium. CYP26A1 expression was present in LSIL but limited to basal and parabasal cells. HSIL cases exhibited strong nuclear expression of CYP26A1 and mixed cytoplasmic expression patterns with widely distributed expression toward the epithelial surface. Importantly, strong cytoplasmic staining of CYP26A1 was observed in 19 of 50 (38%) patients with cervical SCC. Elevated expression of CYP26A1 was significantly associated with younger age (<50 years) and lymph node involvement (pN). Similarly, CYP26A1 was not expressed in non-neoplastic tissues of the head and neck, but strong cytoplasmic staining of CYP26A1 was observed in 52 of 128 (41%) HNC cases. Such strong CYP26A1 expression was significantly associated with the primary tumor stage of carcinomas (pT) and the pathological tumor-node-metastasis (pTNM) stage in HNC. Our results indicated an elevated CYP26A1 expression in malignant and precancerous dysplastic lesions of the human cervix, which also increased with the progression of cervical squamous neoplasia. In addition, this report is the first to demonstrate the increased expression of CYP26A1 in HNC and its significant correlation with primary tumor growth. These data

Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

ClinicalTrials.gov

2017-05-30

Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Cytologic regression in women with atypical squamous cells of unknown significance and negative human papillomavirus test.

PubMed

Wang, Shu; Lang, Jing He; Cheng, Xue Mei

2009-12-01

The aim of this study was to investigate the cytologic regression in women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus test. The 45 women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus at baseline were analyzed about the cytologic regression during 2 years of follow-up. The cumulative rate of cytologic regression was calculated by Kaplan-Meier curves. Of 45 women, the cumulative rates were as follows: 55.6% obtained cytologic regression before 6 months, 84.4% by 1 year, and 95.6% at 2 years. Cytologic regression was not influenced by age, menopausal status, and baseline human papillomavirus load. However, the 1-year cumulative regression rate in women with previous cervical lesions was significantly lower than those without (P=.02), even much lower in women with high-grade intraepithelial neoplasia or worse (P=.008). Most women with atypical squamous cells of unknown significance and negative high-risk human papillomavirus could obtain cytologic regression within 2 years. Women with antecedent cervical lesions need longer time to reach this regression.

Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.

PubMed

Blanco-Luquin, Idoia; Guarch, Rosa; Ojer, Amaya; Pérez-Janices, Noemí; Martín-Sánchez, Esperanza; Maria-Ruiz, Sergio; Monreal-Santesteban, Iñaki; Blanco-Fernandez, Laura; Pernaut-Leza, Eduardo; Escors, David; Guerrero-Setas, David

2015-09-01

Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were tested in ADC and the results were compared with those obtained previously by our group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1 and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The presence of HPV in ADCs was lower than reported previously in SCC and CIN. Patients with RASSF1A hypermethylation showed significantly longer disease-free survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To our knowledge, this is the first description of the EPB41L3 and RASSF2 hypermethylation in ADCs. These results suggest that the involvement of DNA hypermethylation in cervical cancer varies depending on the histological type, which might contribute to explaining the different prognosis of patients with these types of tumors. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Primary Endometrial Squamous Cell Carcinoma In Situ: Report of a rare disease.

PubMed

Jetley, Sujata; Jairajpuri, Zeeba S; Hassan, Mohammad J; Madaan, Garima; Jain, Reena

2015-11-01

Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year's duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

PubMed

Davey, Diane Davis; Greenspan, David L; Kurtycz, Daniel F I; Husain, Mujtaba; Austin, R Marshall

2010-07-01

To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer

ClinicalTrials.gov

2017-06-15

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Keratin 17 in premalignant and malignant squamous lesions of the cervix: proteomic discovery and immunohistochemical validation as a diagnostic and prognostic biomarker

PubMed Central

Escobar-Hoyos, Luisa F; Yang, Jie; Zhu, Jiawen; Cavallo, Julie-Ann; Zhai, Haiyan; Burke, Stephanie; Koller, Antonius; Chen, Emily I; Shroyer, Kenneth R

2014-01-01

Most previously described immunohistochemical markers of cervical high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma may help to improve diagnostic accuracy but have a minimal prognostic value. The goals of the current study were to identify and validate novel candidate biomarkers that could potentially improve diagnostic and prognostic accuracy for cervical HSIL and squamous cell carcinoma. Microdissected tissue sections from formalin-fixed paraffin-embedded normal ectocervical squamous mucosa, low-grade squamous intraepithelial lesion (LSIL), HSIL and squamous cell carcinoma sections were analyzed by mass spectrometry-based shotgun proteomics for biomarker discovery. The diagnostic specificity of candidate biomarkers was subsequently evaluated by immunohistochemical analysis of tissue microarrays. Among 1750 proteins identified by proteomic analyses, keratin 4 (KRT4) and keratin 17 (KRT17) showed reciprocal patterns of expression in the spectrum of cases ranging from normal ectocervical squamous mucosa to squamous cell carcinoma. Immunohistochemical studies confirmed that KRT4 expression was significantly decreased in squamous cell carcinoma compared with the other diagnostic categories. By contrast, KRT17 expression was significantly increased in HSIL and squamous cell carcinoma compared with normal ectocervical squamous mucosa and LSIL. KRT17 was also highly expressed in immature squamous metaplasia and in endocervical reserve cells but was generally not detected in mature squamous metaplasia. Furthermore, high levels of KRT17 expression were significantly associated with poor survival of squamous cell carcinoma patients (Hazard ratio = 14.76, P = 0.01). In summary, both KRT4 and KRT17 expressions are related to the histopathology of the cervical squamous mucosa; KRT17 is highly overexpressed in immature squamous metaplasia, in HSIL, and in squamous cell carcinoma and the level of KRT17 in squamous cell carcinoma may help to identify

Colposcopic and histologic findings in women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

PubMed

Yarandi, Fariba; Izadi Mood, Narges; Mirashrafi, Fatemeh; Eftekhar, Zahra

2004-12-01

The optimal method for managing a patient diagnosed with atypical squamous cells of undetermined significance (ASCUS) has not yet been established. The interim guidelines published by the National Cancer Institute suggest that a patient should be referred for colposcopy after the second ASCUS diagnosis within 2 years. To assess the significance of ASCUS in predicting the presence of underlying squamous intraepithelial lesion (SIL) of the uterine cervix. Women undergoing colposcopy for ASCUS cytology at a teaching hospital in Tehran University, in the years 1998-2001, considered eligible to enter this retrospective study. Of the 266 patients who underwent colposcopy, 28 (11%) had low-grade squamous intraepithelial lesion (LSIL), 16 (6.3%) had high-grade squamous intraepithelial lesion (HSIL) two (0.8%) had squamous cell carcinoma (SCC), and 48 (18.8%) had flat condyloma. Atypical squamous cells of undetermined significance (ASCUS) on a cervical smear is a good marker for detecting underlying SIL and condyloma. Thus, immediate colposcopy and directed biopsy are appropriate follow-up procedures.

A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells

PubMed Central

Zhang, Zhaoxia; Knobloch, Thomas J.; Seamon, Leigh G.; Stoner, Gary D.; Cohn, David E.; Paskett, Electra D.; Fowler, Jeffrey M.; Weghorst, Christopher M.

2014-01-01

Objective Cervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions. Food-based cancer prevention entities, such as black raspberries and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation. Here, we extend the role of black raspberry-mediated chemoprevention to that of cervical carcinogenesis. Methods Three human cervical cancer cell lines, HeLa (HPV16−/HPV18+, adenocarcinoma), SiHa (HPV16+/HPV18−, squamous cell carcinoma) and C-33A (HPV16−/HPV18−, squamous cell carcinoma), were treated with a lyophilized black raspberry ethanol extract (RO-ET) at 25, 50, 100 or 200 μg/ml for 1, 3 and 5 days, respectively. Cell proliferation was measured by WST1 (tetrazolium salt cleavage) assays. Flow cytometry (propidium iodide and Annexin V staining) and fluorescence microscopy analysis were used to measure apoptotic cell changes. Results We found that non-toxic levels of RO-ET significantly inhibited the growth of human cervical cancer cells, in a dose-dependent and time-dependent manner to a maximum of 54%, 52% and 67%, respectively (p<0.05). Furthermore, cell growth inhibition was persistent following short-term withdrawal of RO-ET from the culture medium. Flow cytometry and fluorescence microscopy demonstrated RO-ET-induced apoptosis in all cell lines. Conclusion Black raspberries and their bioactive components represent promising candidates for future phytochemical-based mechanistic pathway-targeted cancer prevention strategies. PMID:21831414

Squamous cell carcinoma causing dorsal atlantoaxial spinal cord compression in a dog

PubMed Central

Miyazaki, Yuta; Aikawa, Takeshi; Nishimura, Masaaki; Iwata, Munetaka; Kagawa, Yumiko

2016-01-01

A 12-year-old Chihuahua dog was presented for cervical pain and progressive tetraparesis. Magnetic resonance imaging revealed spinal cord compression due to a mass in the dorsal atlantoaxial region. Surgical treatment was performed. The mass was histopathologically diagnosed as a squamous cell carcinoma. The dog recovered to normal neurologic status after surgery. PMID:27708441

Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

PubMed Central

Gami, Bhavna; Kubba, Faris; Ziprin, Paul

2014-01-01

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus. PMID:25288893

Comparing Immunohistologic and Demographic Variables of Head and Neck Squamous Cell Carcinoma

DTIC Science & Technology

2015-06-01

HPV 16 and 18 which have a well-established association with cervical cancers . However, HPV 16 accounts for the majority ofHPV...These cancers are now subdivided into HPV associated ( HPV - SCC) and non- HPV associated squamous cell (SCC) carcinomas. HPV -SCG is a distinct entity... cell carcinomas. Laryngoscope 2009; 119(8): 1542-1549. 13. Venuti A, Paolini F. HPV detection methods in head and neck cancer . Head Neck

Atypical Squamous Cells in Liquid-Based Cervical Cytology: Microbiology, Inflammatory Infiltrate, and Human Papillomavirus-DNA Testing.

PubMed

Gomes de Oliveira, Geilson; Eleutério, Renata Mirian Nunes; Silveira Gonçalves, Ana Katherine; Giraldo, Paulo César; Eleutério, José

2018-01-01

The aim of this study was to assess the correlation between atypical squamous cells (ASC) and inflammatory infiltrate and vaginal microbiota using cervical liquid-based cytological (SurePath®) and high-risk human papillomavirus (HR-HPV) tests. A cross-sectional study was conducted using a 6-year database from a laboratory in Fortaleza (Brazil). Files from 1,346 ASC cases were divided into subgroups and results concerning inflammation and vaginal microorganisms diagnosed by cytology were compared with HR-HPV test results. An absence of specific microorganisms (ASM) was the most frequent finding (ASC of undetermined significance, ASC-US = 74%; ASC - cannot exclude high-grade squamous intraepithelial lesion, ASC-H = 68%), followed by bacterial vaginosis (ASC-US = 20%; ASC- H = 25%) and Candida spp. (ASC-US = 6%; ASC-H = 5%). Leukocyte infiltrate was present in 71% of ASC-US and 85% of ASC-H (p = 0.0040), and in these specific cases HR-HPV tests were positive for 65 and 64%, respectively. A positive HR-HPV test was relatively more frequent when a specific microorganism was present, and Candida spp. was associated with HR-HPV-positive results (p = 0.0156), while an ASM was associated with negative HR-HPV results (p = 0.0370). ASC-US is associated with an absence of inflammation or vaginosis, while ASC-H smears are associated with Trichomonas vaginalis and inflammatory infiltrate. A positive HR-HPV is associated with Candida spp. in ASC cytology. © 2017 S. Karger AG, Basel.

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

PubMed Central

Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

2017-01-01

Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

Wnt-11 overexpression promoting the invasion of cervical cancer cells.

PubMed

Wei, Heng; Wang, Ning; Zhang, Yao; Wang, Shizhuo; Pang, Xiaoao; Zhang, Shulan

2016-09-01

Wnt-11 is a positive regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, Wnt-11 expression in cervical cancer has not been well investigated. The aim of this study was to investigate the role of Wnt-11 in cervical tumor proliferation and invasion. This study examined 24 normal cervical squamous epithelia, 29 cervical intraepithelial neoplasia (CIN), and 78 cervical cancer samples. The expression of Wnt-11 was investigated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction analysis. The expression of the high-risk human papilloma virus (HR-HPV) E6 oncoprotein was also investigated by immunohistochemistry. In addition, the expression of Wnt-11, HR-HPV E6, JNK-1, phosphorylated JNK-1(P-JNK1), and β-catenin was examined by western blot analysis following Wnt-11 knockdown or overexpression in HeLa or SiHa cells, respectively. The promotion of cervical cancer cell proliferation and invasion was investigated using the cell counting kit-8 and Matrigel invasion assay, respectively. Wnt-11 and HR-HPV E6 expression increased in a manner that corresponded with the progression of cervical cancer and was significantly correlated with the International Federation of Gynecology and Obstetrics cancer stage, lymph node metastasis, tumor size, and HPV infection. Wnt-11 protein expression was positively associated with HR-HPV E6 protein expression in all 78 cervical cancer samples (P < 0.001). Furthermore, Wnt-11 was positively associated with P-JNK1 expression and promoted cervical cancer cell proliferation and invasion. These observations suggest that the increased Wnt-11 expression observed in cervical cancer cells may lead to the phosphorylation and activation of JNK-1 and significantly promote tumor cell proliferation and cell migration/invasion through activation of the Wnt/JNK pathway. Consequently, Wnt-11 may serve as a novel target for cervical cancer therapy.

Amplification and up-regulation of MIR30D was associated with disease progression of cervical squamous cell carcinomas.

PubMed

Zhou, You; Hao, Yinghua; Li, Yuxia; Li, Ruizhen; Wu, Ruifang; Wang, Shubin; Fang, Zhengyu

2017-03-29

Cervical squamous cell carcinoma (CSCC) is the most frequent type among cervical cancers. Although the altered miRNA miR-30d expression and the amplified chromosome locus of MIR30D, 8q24, have been reported in somatic cancers, the definitive functional impact of such region especially in CSCC remains under-investigated. One hundred thirty-six cases of CSCC tissues and matched adjacent normal ovarian epithelial tissues were assessed in this study. FISH and qPCR were performed to detect the copy number and microRNA expression of MIR30D gene in the collected samples. In in-vitro study, proliferation of CSCC cells were analyzed using WST-1 assay and invasion abilities of CSCC cells were evaluated by transwell assay. In-vivo study using a model of nude mice bearing tumor was also performed. Copy number gains of MIR30D were detected in 22.8% (31 out of 136) of CSCC samples. Copy number of MIR30D was positively correlated with tumor progression. CSCCs with lymph node metastases (LNM) also showed more frequencies (36.4%) of MIR30D amplification than those without LNM (18.4%, p < 0.05). CSCCs with increased copy number of MIR30D also showed a positive correlation with miR-30d up-regulation. Inhibition of miR-30d in CSCC cells led to impaired tumor growth and migration. Copy number amplifications of MIR30D gene and enhanced expression of miR-30d were positively correlated with tumor progression in CSCCs, indicating miR-30d might play an oncomiric role in the progression of CSCC.

E2/E6 ratio and L1 immunoreactivity as biomarkers to determine HPV16-positive high-grade squamous intraepithelial lesions (CIN2 and 3) and cervical squamous cell carcinoma

PubMed Central

2018-01-01

Objective Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ≥cervical intraepithelial neoplasia (CIN) 2 lesions. Methods Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1–3 and squamous cell carcinoma [SCC]) to evaluate the association. Results The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p<0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p<0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p<0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793–0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562–0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826–0.917) for the prediction of ≥CIN2 lesions. Conclusion To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis. PMID:29400024

Virology and Molecular Pathogenesis of Human Papillomavirus (HPV)-Associated Oropharyngeal Squamous Cell Carcinoma

PubMed Central

Miller, Daniel L.; Puricelli, Michael D.; Stack, M. Sharon

2012-01-01

Current literature fully supports HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated head and neck squamous cell carcinoma (HNSCC), and may warrant divergent clinical management compared to HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. This review summarizes the etiology of HPV positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies, and the pathophysiologic significance of altered gene and microRNA expression profiles is warranted. PMID:22452816

[Clinical significance of HPV L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women].

PubMed

Wang, Jiajian; Tian, Qifang; Zhang, Su; Lyu, Liping; Dong, Jie; Lyu, Weiguo

2015-04-01

To explore the clinical significance of human papillomavirus L1 capsid protein detection in cervical exfoliated cells in high-risk HPV positive women. From November 2012 to June 2013, 386 high-risk HPV positive (detected by hybrid capture II) cases were enrolled as eligible women from Huzhou Maternity & Child Care Hospital and Women's Hospital, School of Medicine, Zhejiang University. All eligible women underwent liquid-based cytology (ThinPrep) followed by colposcopy. Biopsies were taken if indicated. Cervical exfoliated cells were collected for HPV L1 capsid protein detection by immunocytochemistry. Expression of HPV L1 capsid protein in groups with different histological diagnosis were compared, and the role of HPV L1 capsid protein detection in cervical exfoliated cells in cervical lesions screening was accessed. Total 386 enrolled eligible women were finally diagnosed histologically as follwed: 162 normal cervix, 94 low-grade squamous intraepithelial lesion (LSIL), 128 high-grade squamous intraepithelial lesion (HSIL) and 2 squamous cervical cancer (SCC). The positive expression rate of HPV L1 in HSIL+ (HSIL or worse) group was significantly lower than that in LSIL- (LSIL or better) group (19.2% vs 66.4%, P=0.000). While identifying HSIL+ in HPV positive cases and compared with cytology, HPV L1 detection resulted in significant higher sensitivity (80.77% vs 50.77%, P=0.000) and negative predictive value (NPV; 87.18% vs 76.47%, P=0.004), significant lower specificity (66.41% vs 81.25%, P=0.000), and comparable positive predictive value (PPV; 54.97% vs 57.89%, P=0.619). To identify HSIL+ in HPV-positive/cytology-negative women, the sensitivity, specificity, PPV, and NPV of HPV L1 detection were 87.50%, 61.54%, 41.18%, and 94.12% respectively, while 80.00%, 86.36%, 80.00% and 86.36% respectively in HPV-positive/atypical squamous cell of undetermined significance (ASCUS) women. HPV L1 capsid detection in cervical exfoliated cells have a role in cervical lesions

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

PubMed

Taylor, R J; Wahl, R L; Sharma, P K; Bradford, C R; Terrell, J E; Teknos, T N; Heard, E M; Wolf, G T; Chepeha, D B

2001-08-01

To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. Tertiary referral center. Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

PubMed

Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

2009-05-01

A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study.

PubMed

Wang, Jiangrong; Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

2016-02-11

To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Nationwide population based cohort study. Cancer and population registries in Sweden. 3,054,328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2,899,968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology

Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study

PubMed Central

Andrae, Bengt; Sundström, Karin; Ström, Peter; Ploner, Alexander; Elfström, K Miriam; Arnheim-Dahlström, Lisen; Dillner, Joakim; Sparén, Pär

2016-01-01

Objectives To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. Design Nationwide population based cohort study. Setting Cancer and population registries in Sweden. Participants 3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. Main outcome measures Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. Results The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment

Rate of regional nodal metastases of cutaneous squamous cell carcinoma in the immunosuppressed patient.

PubMed

McLaughlin, Eamon J; Miller, Lauren; Shin, Thuzar M; Sobanko, Joseph F; Cannady, Steven B; Miller, Christopher J; Newman, Jason G

Immunosuppressed solid organ transplant recipients (SOTRs) have an increased risk of developing cutaneous squamous cell carcinomas (cSCCs) with metastatic potential. This study sought to determine the rate of regional lymph node involvement in a large cohort of solid organ transplant patients with cutaneous head and neck squamous cell carcinoma. A retrospective chart review was performed on solid organ transplant patients with head and neck cutaneous squamous cell carcinoma treated at a tertiary academic medical center from 2005 to 2015. 130 solid organ transplant patients underwent resection of 383 head and neck cutaneous squamous cell carcinomas. The average age of the patient was 63. Seven patients (5%) developed regional lymph node metastases (3 parotid, 4 cervical lymph nodes). The mean time from primary tumor resection to diagnosis of regional lymphatic disease was 6.7months. Six of these patients underwent definitive surgical resection followed by adjuvant radiation; one patient underwent definitive chemoradiation. 6 of the 7 patients died of disease progression with a mean survival of 15months. The average follow up time was 3years (minimum 6months). Solid organ transplant recipients with cutaneous squamous cell carcinoma of the head and neck develop regional lymph node metastasis at a rate of 5%. Regional lymph node metastasis in this population has a poor prognosis and requires aggressive management and surveillance. Copyright © 2017 Elsevier Inc. All rights reserved.

Brachytherapy after salvage surgery in cases with large isolated cervical recurrence of squamous cell carcinoma in the previously irradiated neck.

PubMed

Miroir, Jessica; Biau, Julian; Saroul, Nicolas; Moreira, Jean-François; Russier, Marc; Lapeyre, Michel

2016-09-01

Perioperative brachytherapy after salvage surgery is a therapeutic option in patients with cervical relapse of a primary, controlled, previously irradiated head and neck squamous cell carcinoma. The purpose of this study was to analyze the outcome of this treatment. Between 2008 and 2013, 8 patients underwent cervical brachytherapy after neck dissection. The mean node size was 5.5 cm. Recurrence occurred in an irradiated field (median dose, 50 Gy). Brachytherapy was performed with (192) iridium and dosimetry in accord with the rules of the Paris system. The dose was 60 to 62.7 Gy on the reference isodose. The mean follow-up was 17 months. The median overall survival (OS) was 12 months. The OS was 19% at 2 years and 0% at 5 years. A grade 5 postoperative adverse event occurred in 1 patient. At 6 months, all patients had a grade 3 neck soft tissue fibrosis. One patient had a lethal hemorrhage at 56 months. Brachytherapy is toxic in this population with poor OS. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2490-E2494, 2016. © 2016 Wiley Periodicals, Inc.

Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

ClinicalTrials.gov

2014-12-29

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Characteristic findings of cervical Papanicolaou tests from transgender patients on androgen therapy: Challenges in detecting dysplasia.

PubMed

Adkins, B D; Barlow, A B; Jack, A; Schultenover, S J; Desouki, M M; Coogan, A C; Weiss, V L

2018-02-28

The characteristic features of Papanicolaou (Pap) tests collected from female-to-male (FTM) transgender patients on androgen therapy have not been well defined in the literature. FTM transgender patients require cervical cancer screening with the same recommended frequency as cis-gender females. Dysplasia remains challenging to differentiate from atrophy. Without pertinent history, the atrophic findings in younger transgender patients can be misinterpreted as high-grade dysplasia. A review of all cervical Pap tests of transgender patients receiving androgen therapy (2010-2017) was performed. Bethesda diagnosis, cytomorphological features, HPV testing and cervical biopsy results were reviewed. Eleven transgender patients receiving androgen therapy were identified with 23 cervical Pap tests, 11 HPV tests and five cervical biopsies performed. A review of the Pap tests demonstrated: 57% negative for intraepithelial lesion; 13% unsatisfactory; 13% atypical squamous cells of undetermined significance; 13% atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion; and 4% high-grade squamous intraepithelial lesion. The rates of abnormal tests were higher than our age-matched cis-gender atrophic cohort rates of unsatisfactory (0.5%), atypical squamous cells of undetermined significance (7%), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (0%) and high-grade squamous intraepithelial lesion (0.5%). The cytological findings from liquid-based preparations included dispersed and clustered parabasal-type cells, scattered degenerated cells, smooth evenly dispersed chromatin, and occasional mild nuclear enlargement and irregularity. Dysplastic cells had larger nuclei, hyperchromatic clumped chromatin, and more irregular nuclear contours. The evaluation of dysplasia can be challenging on Pap tests from transgender patients on androgen therapy. The cohort evaluated had higher rates of unsatisfactory and abnormal Pap tests

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion

PubMed Central

Ryu, Ki-Jin; Lee, Sanghoon; Min, Kyung-Jin; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan

2015-01-01

Background. Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results. Materials and Methods. A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013. Results. ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status. Conclusion. If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive. Implications for Practice: Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

PubMed Central

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck.

PubMed

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management.

Uneven distribution of human papillomavirus 16 in cervical carcinoma in situ and squamous cell carcinoma in older females: A retrospective database study

PubMed Central

ANDERSSON, SONIA; MINTS, MIRIAM; GYLLENSTEN, ULF; LINDELL, MONICA; GUSTAVSSON, INGER; LAMBE, MATS; WILANDER, ERIK

2014-01-01

Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18/45 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females. PMID:25202362

Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

ClinicalTrials.gov

2017-08-08

Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer

ClinicalTrials.gov

2018-04-20

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions.

PubMed

Sopracordevole, F; Clemente, N; Alessandrini, L; Di Giuseppe, J; Cigolot, F; Buttignol, M; Ciavattini, A; Canzonieri, V

2017-03-01

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC). The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series. Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult "usual-type" AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5). In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7-206 months) and no cases of progression to HCGIN or AC were observed. In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

ClinicalTrials.gov

2018-05-23

Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

p16 expression in follicular dendritic cell sarcoma: a potential mimicker of human papillomavirus-related oropharyngeal squamous cell carcinoma.

PubMed

Zhang, Lingxin; Yang, Chen; Lewis, James S; El-Mofty, Samir K; Chernock, Rebecca D

2017-08-01

Follicular dendritic cell sarcoma is a rare mesenchymal neoplasm that most commonly occurs in cervical lymph nodes. It has histologic and clinical overlap with the much more common p16-positive human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx, which characteristically has nonkeratinizing morphology and often presents as an isolated neck mass. Not surprisingly, follicular dendritic cell sarcomas are commonly misdiagnosed as squamous cell carcinoma. Immunohistochemistry is helpful in separating the 2 entities. Follicular dendritic cell sarcoma expresses dendritic markers such as CD21 and CD23 and is almost always cytokeratin negative. However, in many cases of HPV-related oropharyngeal carcinoma, only p16 immunohistochemistry as a prognostic and surrogate marker for HPV is performed. p16 expression in follicular dendritic cell sarcoma has not been characterized. Here, we investigate the expression of p16 in follicular dendritic cell sarcoma and correlate it with retinoblastoma protein expression. A pilot study of dendritic marker expression in HPV-related oropharyngeal squamous cell carcinoma was also performed. We found that 4 of 8 sarcomas expressed p16 with strong and diffuse staining in 2 cases. In 2 of the 4 cases, p16 expression corresponded to loss of retinoblastoma protein expression. Dendritic marker expression (CD21 and CD23) was not found in HPV-related oropharyngeal squamous cell carcinomas. As such, positive p16 immunohistochemistry cannot be used as supportive evidence for the diagnosis of squamous cell carcinoma as strong and diffuse p16 expression may also occur in follicular dendritic cell sarcoma. Cytokeratins and dendritic markers are critical in separating the two tumor types. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation Among Six Biologic Factors (p53, p21{sup WAF1}, MIB-1, EGFR, HER2, and Bcl-2) and Clinical Outcomes After Curative Chemoradiation Therapy in Squamous Cell Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamashita, Hideomi; Murakami, Naoya; Asari, Takao

Purpose: The expressions of six cell-cycle-associated proteins were analyzed in cervical squamous cell carcinomas in correlation in a search for prognostic correlations in tumors treated with concurrent chemoradiation therapy (cCRT). Methods and Materials: The expressions of p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2), and Bcl-2 were studied using an immunohistochemical method in 57 cases of cervical squamous cell carcinoma treated with cCRT. Patients received cCRT between 1998 and 2005. The mean patient age was 61 years (range, 27-82 years). The number of patients with Stage II, III, andmore » IVA disease was 18, 29, and 10, respectively. Results: The number of patients with tumors positive for p53, p21/waf1/cip1, MIB-1, EGFR, HER2, and Bcl-2 was 26, 24, 49, 26, 13, and 11, respectively; no significant correlation was noted. The 5-year overall survival rates of HER2-positive and -negative patients was 76% vs. 44%, which was of borderline significance (p = 0.0675). No significant correlation was noted between overall survival and expressions of p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2. No correlation was observed between local control and expression of any of the proteins. Conclusion: Expression of HER2 protein had a weak impact of borderline significance on overall survival in squamous cell carcinoma of the uterine cervix treated with cCRT. However, no clinical associations could be established for p53, p21/waf1/cip1, MIB-1, EGFR, and Bcl-2 protein expressions.« less

Clinical impact of atypical squamous cells of undetermined significance. A cytohistologic comparison.

PubMed

Lousuebsakul, V; Knutsen, S M; Gram, I T; Akin, M R

2000-01-01

To assess the percentage of squamous intraepithelial lesions (SILs) in the atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis. From January 1994 to December 1995, 421 cervical Pap smears with a diagnosis of ASCUS were followed with cervical biopsies within three months. The ASCUS cytologic diagnosis was correlated with the histologic findings and stratified according to age group, previous abnormal history and cell type of ASCUS (squamoid vs. metaplastic). Histologic diagnosis showed that of ASCUS diagnoses, 13% were normal, 34% were reactive, 4.8% were atypical, 43% were low grade SIL, 4% were high grade SIL, 1% were carcinoma in situ, and none were invasive lesions. The patients in the youngest group, up to 25 years, demonstrated the highest percentage of SIL. Patients with a previous abnormal gynecologic history showed a higher percentage of SIL than those without an abnormal history. SILs were observed in 51.5% of squamoid ASCUS and 36.5% of metaplastic ASCUS. Forty-eight percent of females having an ASCUS diagnosis on Pap smears had SIL and thus a preneoplastic lesion. The highest percentage of SIL was found in females 25 years and younger. Our findings suggest that an ASCUS diagnosis warrants ongoing follow-up.

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions

PubMed Central

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-01-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c+ pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR+ pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR+ pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c+ pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions.

PubMed

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-03-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c + pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR + pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR + pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c + pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the

[Expression of Ki-67 and P53 protein in oral squamous cell carcinoma and its clinical significance].

PubMed

He, Wei; Xiao, Yan; Chen, Wei-min

2015-04-01

To investigate the clinical and pathological features and its relationship with the expression of Ki-67 and p53 protein in oral squamous cell carcinoma. Immunohistochemical SP staining method was used to quantify the protein expression levels of Ki-67 and p53 protein in 10 cases of normal oral mucosa, 16 cases of oral leukoplakia (OLK) tissue, and 48 cases of oral squamous cell carcinoma. The relationship of the expression of Ki-67 and p53 protein to clinical and pathological data was analyzed, and SPSS17.0 software package was used for statistical analysis. The positive expression rate of Ki-67 protein in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma was 30%, 56.3% and 79.2%, respectively; The positive expression rate of p53 was 0%, 43.8%, and 70.8%, respectively; Ki-67 and p53 expression had significant difference among normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma (P<0.05); The expression of Ki-67 protein was significantly elevated with tumor stage, differentiation and cervical lymph node metastasis (P<0.05); The expression of p53 protein was significantly related to the degree of tumor differentiation (P<0.05); The expression of Ki-67 and p53 was positively correlated in oral squamous cell carcinoma (P<0.05). The high expression of Ki-67 and p53 protein in oral squamous cell carcinoma tissues may play an important role in the development of oral squamous cell carcinoma.

Inhibiting CD146 by its Monoclonal Antibody AA98 Improves Radiosensitivity of Cervical Cancer Cells.

PubMed

Cheng, Huawen

2016-09-20

BACKGROUND Cervical cancer is one of the major causes of cancer death of females worldwide. Radiotherapy is considered effective for cervical cancer treatment, but the low radiosensitivity found in some cases severely affects therapeutic outcomes. This study aimed to reveal the role of CD146, an important adhesion molecule facilitating tumor angiogenesis, in regulating radiosensitivity of cervical cancer cells. MATERIAL AND METHODS CD146 protein expression was compared in normal cells, cervical cancer cells with lower radiosensitivity, and cervical cancer cells with higher sensitivity from cervical squamous cell carcinoma patients. Anti-CD146 monoclonal antibody AA98 was used to inhibit CD146 in human cervical cancer SiHa cells with relatively low radiosensitivity, and then the cell survival and apoptosis changes after radiation were detected by colony formation assay and flow cytometry. RESULTS CD146 protein was significantly up-regulated in cervical cancer cells (P<0.001), especially in cancer cells with lower radiosensitivity. The SiHa cells treated with AA98 showed more obvious inhibition in cell survival (P<0.05) and promotion in cell apoptosis (P<0.01) after radiation, compared to the untreated cells. More dramatic changes in apoptotic factors Caspase 3 and Bcl-XL were also detected in AA98-treated cells. CONCLUSIONS These results indicate that inhibiting CD146 improves the effect of radiation in suppressing SiHa cells. This study shows the potential of CD146 as a target for increasing radiosensitivity of cervical cancer cells, which might allow improvement in treatment outcome in cervical cancer. Further studies are necessary for understanding the detailed mechanism of CD146 in regulating radiosensitivity.

Significance of CD133 positive cells in four novel HPV-16 positive cervical cancer-derived cell lines and biopsies of invasive cervical cancer.

PubMed

Javed, Shifa; Sharma, Bal Krishan; Sood, Swati; Sharma, Sanjeev; Bagga, Rashmi; Bhattacharyya, Shalmoli; Rayat, Charan Singh; Dhaliwal, Lakhbir; Srinivasan, Radhika

2018-04-02

Cervical cancer is a major cause of cancer-related mortality in women in the developing world. Cancer Stem cells (CSC) have been implicated in treatment resistance and metastases development; hence understanding their significance is important. Primary culture from tissue biopsies of invasive cervical cancer and serial passaging was performed for establishing cell lines. Variable Number Tandem Repeat (VNTR) assay was performed for comparison of cell lines with their parental tissue. Tumorsphere and Aldefluor assays enabled isolation of cancer stem cells (CSC); immunofluorescence and flow cytometry were performed for their surface phenotypic expression in cell lines and in 28 tissue samples. Quantitative real-time PCR for stemness and epithelial-mesenchymal transition (EMT) markers, MTT cytotoxicity assay, cell cycle analysis and cell kinetic studies were performed. Four low-passage novel cell lines designated RSBS-9, - 14 and - 23 from squamous cell carcinoma and RSBS-43 from adenocarcinoma of the uterine cervix were established. All were HPV16+. VNTR assay confirmed their uniqueness and derivation from respective parental tissue. CSC isolated from these cell lines showed CD133 + phenotype. In tissue samples of untreated invasive cervical cancer, CD133 + CSCs ranged from 1.3-23% of the total population which increased 2.8-fold in radiation-resistant cases. Comparison of CD133 + with CD133 - bulk population cells revealed increased tumorsphere formation and upregulation of stemness and epithelial-mesenchymal transition (EMT) markers with no significant difference in cisplatin sensitivity. Low-passage cell lines developed would serve as models for studying tumor biology. Cancer Stem Cells in cervical cancer display CD133 + phenotype and are increased in relapsed cases and hence should be targeted for achieving remission.

Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

ClinicalTrials.gov

2018-04-25

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Vulvar Cancer AJCC v7; Stage IIA1 Cervical Cancer AJCC v7; Stage IIA2 Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Vulvar Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Vulvar Cancer AJCC v7; Stage IIIC Vulvar Cancer AJCC v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vulvar Cancer AJCC v7; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

ClinicalTrials.gov

2017-05-03

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: a case report.

PubMed

Wang, Yinong; Otis, Christopher N; Florence, Roxanne R

2015-01-01

Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high-grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice. © 2014 Wiley Periodicals, Inc.

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary: outcomes and patterns of failure.

PubMed

Mistry, R C; Qureshi, S S; Talole, S D; Deshmukh, S

2008-01-01

Management of cervical lymph nodes metastases of squamous cell carcinoma (SCC) from primary of unknown origin (PUO) is contentious and there is insignificant data from India on this subject. To present experience of management of these patients treated with curative intent at a single institution. Retrospective study of patients treated between 1989-1994 in a tertiary referral cancer centre. Eighty-nine patients were evaluated in the study period and their survival compared with patients with common sites of primary in the head and neck with comparable node stage. Kaplan-Meier method. The clinical stage of the neck nodes at presentation was N1 in 11%, N2a in 28.5%, N2b in 22.5%, N3 in 35% and Nx in 3.4% patients. All patients underwent surgery and 70 patients received more than 40Gy postoperative radiotherapy. Twenty-nine (32.6%) patients had relapse of which 19 (21%) were in the neck. Postoperative radiotherapy did not influence the neck relapse (p=0.72). Primary was detected in 13 patients (14.6%) on subsequent follow up. The overall five and eight-years survival was 55% and 51% respectively. The overall five-year survival was better compared to patients with known primary with comparable node stage. Patients with cervical lymph nodes metastases of SCC from PUO have reasonable survival and low rate of development of subsequent primary when treated with surgery and radiotherapy. The overall survival is comparable to that of patients with known primary and hence an attempt at cure should always be made.

Computed tomography detection of extracapsular spread of squamous cell carcinoma of the head and neck in metastatic cervical lymph nodes.

PubMed

Carlton, Joshua A; Maxwell, Adam W; Bauer, Lyndsey B; McElroy, Sara M; Layfield, Lester J; Ahsan, Humera; Agarwal, Ajay

2017-06-01

Background and purpose In patients with squamous cell carcinoma of the head and neck (HNSCC), extracapsular spread (ECS) of metastases in cervical lymph nodes affects prognosis and therapy. We assessed the accuracy of intravenous contrast-enhanced computed tomography (CT) and the utility of imaging criteria for preoperative detection of ECS in metastatic cervical lymph nodes in patients with HNSCC. Materials and methods Preoperative intravenous contrast-enhanced neck CT images of 93 patients with histopathological HNSCC metastatic nodes were retrospectively assessed by two neuroradiologists for ECS status and ECS imaging criteria. Radiological assessments were compared with histopathological assessments of neck dissection specimens, and interobserver agreement of ECS status and ECS imaging criteria were measured. Results Sensitivity, specificity, positive predictive value, and accuracy for overall ECS assessment were 57%, 81%, 82% and 67% for observer 1, and 66%, 76%, 80% and 70% for observer 2, respectively. Correlating three or more ECS imaging criteria with histopathological ECS increased specificity and positive predictive value, but decreased sensitivity and accuracy. Interobserver agreement for overall ECS assessment demonstrated a kappa of 0.59. Central necrosis had the highest kappa of 0.74. Conclusion CT has moderate specificity for ECS assessment in HNSCC metastatic cervical nodes. Identifying three or more ECS imaging criteria raises specificity and positive predictive value, therefore preoperative identification of multiple criteria may be clinically useful. Interobserver agreement is moderate for overall ECS assessment, substantial for central necrosis. Other ECS CT criteria had moderate agreement at best and therefore should not be used individually as criteria for detecting ECS by CT.

Squamous cell carcinoma - invasive (image)

MedlinePlus

This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

MRI and PET Imaging in Predicting Treatment Response in Patients With Stage IB-IVA Cervical Cancer

ClinicalTrials.gov

2018-06-18

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cervical Undifferentiated Carcinoma; Recurrent Cervical Carcinoma; Stage IB2 Cervical Cancer; Stage II Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

ClinicalTrials.gov

2017-08-23

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer

NASA Astrophysics Data System (ADS)

Muthuvelu, K.; Shanmugam, Sivabalan; Koteeswaran, Dornadula; Srinivasan, S.; Venkatesan, P.; Aruna, Prakasarao; Ganesan, Singaravelu

2011-03-01

In this study the diagnostic potential of synchronous luminescence spectroscopy (SLS) technique for the characterization of normal and different pathological condition of cervix viz., moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) and well differentiated squamous cell carcinoma (WDSSC). Synchronous fluorescence spectra were measured for 70 abnormal cases and 30 normal subjects. Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC and WDSCC cervical blood formed elements were obtained. The synchronous luminescence spectra of formed elements of normal and abnormal cervical cancer patients were subjected to statistical analysis. Synchronous luminescence spectroscopy provides 90% sensitivity and 92.6% specificity.

Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

PubMed

Tokmak, Aytekin; Guzel, Ali Irfan; Ozgu, Emre; Oz, Murat; Akbay, Serap; Erkaya, Salim; Gungor, Tayfun

2014-01-01

To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

PubMed

Kim, S H; Lee, J M; Yun, H G; Park, U S; Hwang, S U; Pyo, J-S; Sohn, J H

2017-02-01

The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients. © 2016 John Wiley & Sons Ltd.

Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

ClinicalTrials.gov

2018-02-21

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Cervical Cancer AJCC v6 and v7

Microanatomy of the cervical and anorectal squamocolumnar junctions: a proposed model for anatomical differences in HPV-related cancer risk

PubMed Central

Yang, Eric J.; Quick, Matthew C.; Hanamornroongruang, Suchanan; Lai, Keith; Doyle, Leona; McKeon, Frank D.; Xian, Wa; Crum, Christopher P.; Herfs, Michael

2015-01-01

Human papilloma virus (HPV) infection causes cancers and their precursors (high grade squamous intraepithelial lesions) near cervical and anal squamocolumnar junctions. Recently described cervical squamocolumnar junctions cells are putative residual embryonic cells near the cervical transformation zone. These cells appear multipotential and share an identical immunophenotype (strongly CK7-positive) with over 90% of high grade squamous intraepithelial lesions and cervical carcinomas. However, because the number of new cervical cancers discovered yearly world-wide is 17-fold that of anal cancer, we posed the hypothesis that this difference in cancer risk reflects differences in the transition zones at the two sites. The microanatomy of the normal anal transformation zone (n = 37) and topography and immunophenotype of anal squamous neoplasms (n = 97) were studied. A discrete anal transition zone was composed of multi-layered CK7-positive/p63-negative superficial columnar cells and an uninterrupted layer of CK7-negative/p63-positive basal cells. The CK7-negative/p63-positive basal cells were continuous with – and identical in appearance to - the basal cells of the mature squamous epithelium. This was in contrast to the cervical squamocolumnar junction, that harbored a single-layered CK7-positive/p63-negative squamocolumnar junction cell population. Of the 97 Anal intraepithelial neoplasia/squamous cell carcinomas evaluated, only 27% (26/97) appeared to originate near the anal transition zone and only 23% (22/97) were CK7-positive. This study thus reveals two fundamental differences between the anus and cervix: 1) the anal transition zone does not harbor a single monolayer of residual un-differentiated embryonic cells and 2) the dominant tumor immuno-phenotype is in keeping with an origin in metaplastic (CK7-negative) squamous rather than squamocolumnar junction (CK7-positive) epithelium. The implication is that at birth, the embryonic cells in the anal transition

FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting β-catenin through mRNA demethylation.

PubMed

Zhou, Shun; Bai, Zhou-Lan; Xia, Di; Zhao, Zhi-Jun; Zhao, Ren; Wang, Yan-Yang; Zhe, Hong

2018-05-01

The role of N 6 -methyladenosine (m 6 A) demethylase fat mass and obesity-associated protein (FTO) in the regulation of chemo-radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of β-catenin by reducing m 6 A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity. Clinically, the prognostic value of FTO for overall survival is found to be dependent on β-catenin expression in human CSCC samples. Taken together, these findings uncover a critical function for FTO and its substrate m 6 A in the regulation of chemo-radiotherapy resistance, which may bear potential clinical implications for CSCC treatment. © 2018 Wiley Periodicals, Inc.

CLDN1 expression in cervical cancer cells is related to tumor invasion and metastasis.

PubMed

Zhang, Wei-Na; Li, Wei; Wang, Xiao-Li; Hu, Zheng; Zhu, Da; Ding, Wen-Cheng; Liu, Dan; Li, Ke-Zhen; Ma, Ding; Wang, Hui

2016-12-27

Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.

Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

NASA Astrophysics Data System (ADS)

Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

2014-08-01

We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klopp, Ann H.; Jhingran, Anuja; Ramdas, Latha

2008-05-01

Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified thatmore » were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay.« less

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out.

PubMed

Cytryn, Andréa; Russomano, Fábio Bastos; Camargo, Maria José de; Zardo, Lucília Maria Gama; Horta, Nilza Maria Sobral Rebelo; Fonseca, Rachel de Carvalho Silveira de Paula; Tristão, Maria Aparecida; Monteiro, Aparecida Cristina Sampaio

2009-09-01

The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

PubMed

Wong, O G; Ho, M W; Tsun, O K; Ng, A K; Tsui, E Y; Chow, J N; Ip, P P; Cheung, A N

2018-03-26

To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions. © 2018 John Wiley & Sons Ltd.

Prevalence of cervical neoplastic lesions and Human Papilloma Virus infection in Egypt: National Cervical Cancer Screening Project

PubMed Central

Abd El All, Howayda S; Refaat, Amany; Dandash, Khadiga

2007-01-01

Background Data from Egyptian studies provide widely varying estimates on the prevalence of pre-malignant and malignant cervical abnormalities and human papilloma virus (HPVs) infection. To define the prevalence and risk factors of pre-invasive and invasive cervical cancer (cacx), a community based full-scale cross sectional, household survey including 5453 women aged between 35 and 60 years was conducted. Methods The study period was between February 2000 and December 2002. Initially, conventional Papanicolaou (Pap) smears were evaluated using the Bethesda system (TBS), followed by colposcopic guided biopsy (CGB) for all epithelial abnormalities (EA). In a third step, HPV was tested on all EA by in-situ hybridization (ISH) using first the broad spectrum HPV probe recognizing HPVs 6, 11, 16, 18, 30, 31, 35, 45, 51 and 52 followed by subtyping with probes 6/11, 16/18 and 31/33. Lastly, unequivocal cases were immunostained for herpes simplex type-2 (HSV-2), cytomegalovirus (CMV), and human immunodeficiency virus (HIV). Results EA representing 7.8% (424/5453), were categorized into atypical squamous cell of undetermined significance (ASCUS) (34.4%), atypical glandular cell of undetermined significance (AGCUS) (15.3%), combined ASCUS and AGCUS (3.1%), low grade squamous intraepithelial lesions (SIL) (41.0%), high grade SIL (5.2%) and invasive lesions (1%). CGB of EA (n = 281) showed non neoplastic lesions (12.8%), atypical squamous metaplasia (ASM) (19.2%), cervical intraepithelial neoplasia I (CIN) (44.4%), CIN II (4.4%), CINIII (2.8%), endocervical lesions (5.2%), combined squamous and endocervical lesions (10.0%), invasive squamous cell carcinoma (SCC) (0.02%) and extranodal marginal zone B cell lymphoma (MZBCL) (0.02%). The overall predictive value of cytology was 87% while the predictive value for high grade lesions was 80%. On histological basis, HPVs were present in 94.3% of squamous lesions while it was difficult to be identified in endocervical ones. ISH

Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

ClinicalTrials.gov

2017-08-23

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Chemotherapeutic Agent Toxicity; Cognitive Side Effects of Cancer Therapy; Psychological Impact of Cancer; Radiation Toxicity; Sexual Dysfunction and Infertility; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

Tumor necrosis factor-alpha stimulates the production of squamous cell carcinoma antigen in normal squamous cells.

PubMed

Numa, F; Takeda, O; Nakata, M; Nawata, S; Tsunaga, N; Hirabayashi, K; Suminami, Y; Kato, H; Hamanaka, S

1996-01-01

Squamous cell carcinoma (SCC) antigen, a tumor marker of squamous cell carcinoma, is also increased in several nonmalignant skin lesions, e.g. pemphigus. The aim of the present investigation was to determine if tumor necrosis factor-alpha (TNF-alpha), one of the important environmental factors, stimulated the production of SCC antigen in the normal squamous cells. The exposure of normal human epidermal keratinocytes to TNF-alpha (100 IU/ml) for 72 h greatly increased the SCC antigen production. The stimulatory effect of TNF-alpha (1,000 IU/ml) on the production of SCC antigen was also observed in the normal squamous epithelium tissue. These results would be helpful for understanding the increase of SCC antigen in several nonmalignant skin disorders.

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

PubMed

Pang, Tianyun; Li, Min; Zhang, Ye; Yong, Weiwei; Kang, Haixian; Yao, Yunhong; Hu, Xinrong

2017-10-01

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.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients

PubMed Central

Bae, Su-Mi; Min, Hyun-Jin; Ding, Guo Hua; Kwak, Sun-Young; Cho, Young-Lae; Nam, Kye-Hyun; Park, Choong Hak; Kim, Yong-Wan; Kim, Chong-Kook; Han, Byoung-Don; Lee, Young-Joo; Kim, Do Kang

2006-01-01

Purpose Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two- dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI- TOF) mass spectrometer. Materials and Methods Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software™. The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. Results A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. Conclusion 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC. PMID:19771267

The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.

PubMed

Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe; Lajer, Christel Bræmer

2016-12-01

There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stomatin-like protein 2 is overexpressed in cervical cancer and involved in tumor cell apoptosis

PubMed Central

Deng, Huan; Deng, Yongjian; Liu, Feiye; Chen, Jie; Li, Zheng; Zhao, Kelei; Guan, Xiaoqian; Liang, Weijiang

2017-01-01

Stomatin-like protein 2 (SLP-2) is overexpressed in numerous types of human cancer and previous studies revealed that SLP-2 may function in mitochondria. The purpose of the present study was to evaluate the expression of SLP-2 in cervical cancer and the association between SLP-2 expression and clinical features, in addition to investigating the role of SLP-2 in the apoptosis of cervical cancer cells. The expression profile of SLP-2 was determined by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The effect of SLP-2 on cell apoptosis induced by chemotherapeutics in cervical cancer cells was evaluated using Annexin V staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assays. The results indicated that SLP-2 expression in cervical cancer was significantly upregulated at the mRNA and protein levels, compared with that in normal cervical tissues. Immunohistochemical analysis revealed significant correlation between SLP-2 protein expression and clinical characteristics, including the squamous cell carcinoma antigen (P=0.003), deep stromal invasion (P=0.021), lymphovascular space involvement (P=0.044) and pelvic lymph node metastasis (P<0.001), which served as independent prognostic factors for predicting the shortening of overall survival time in patients with early-stage cervical cancer. In addition, TUNEL and Annexin V binding assays revealed that silencing SLP-2 expression significantly enhanced the sensitivity of cervical cancer cells to apoptosis induced by chemotherapeutics. Taken together, the results of the present study suggest that SLP-2 may be a progressive gene in the development of cervical cancer. Overexpression of SLP-2 serves an important role in the apoptosis of human cervical cancer cells. PMID:29181097

Cervical Dysplasia

PubMed Central

Carmichael, John A.

1983-01-01

Invasive squamous carcinoma of the cervix is preceded by a series of premalignant changes described as mild, moderate, or severe dysplasia, and carcinoma in situ. These premalignant states are identified by cervical cytology, diagnosed by colposcopy and if effectively treated, can prevent invasive squamous carcinoma of the cervix. Because of the apparent biological variation of the premalignant states, even the most aggressive cervical screening program cannot be expected to eliminate all invasive squamous cancer of the cervix. Optimal results of a cervical screening program will be achieved when all women under 35 years of age and sexually active have an annual cytological smear; the cytology is screened by a laboratory with high quality control; the patient's positive cytology is accurately assessed by an experienced colposcopist, and the premalignant lesion is effectively treated. PMID:21283455

RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1α release, and efficient paracrine dendritic cell activation.

PubMed

Schmidt, Susanne V; Seibert, Stefanie; Walch-Rückheim, Barbara; Vicinus, Benjamin; Kamionka, Eva-Maria; Pahne-Zeppenfeld, Jennifer; Solomayer, Erich-Franz; Kim, Yoo-Jin; Bohle, Rainer M; Smola, Sigrun

2015-04-20

Previous studies have shown that cervical cancer cells only release low levels of pro-inflammatory cytokines owing to infection with human papillomaviruses. This results in low immunogenicity of the cancer cells. The viral dsRNA analog PolyIC has been suggested as a promising adjuvant for cervical cancer immunotherapy. However, little is known about the molecular requirements resulting in successful immune activation. Here, we demonstrate that stimulation of cervical cancer cells with PolyIC induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. Necroptotic cancer cells released interleukin-1α (IL-1α), which was required for powerful activation of dendritic cells (DC) to produce IL-12, a cytokine critical for anti-tumor responses. Again both, IL-1α release and DC activation, were strictly dependent on RIPK3 expression in the tumor cells. Of note, our in situ analyses revealed heterogeneous RIPK3 expression patterns in cervical squamous cell carcinomas and adenocarcinomas. In summary, our study identified a novel RIPK3-dependent mechanism that explains how PolyIC-treatment of cervical cancer cells leads to potent DC activation. Our findings suggest that the RIPK3 expression status in cervical cancer cells might critically influence the outcome of PolyIC-based immunotherapeutic approaches and should therefore be assessed prior to immunotherapy.

Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

2015-12-01

The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

Clinical significance of atypical squamous cells cannot exclude high grade squamous intraepithelial lesion with histologic correlation-: a 9-year experience.

PubMed

Selvaggi, Suzanne M

2013-11-01

Atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H) is a recognized category in the 2001 Bethesda Nomenclature System for cervical cytology. Although current ASCCP guidelines recommend colposcopic follow-up, more recent studies are suggesting prior triage for HPV-DNA analysis. We report on our experience at the University of Wisconsin Hospital and Clinics. From January 1, 2003 through December 31, 2011 (9-y), the cytopathology laboratory processed 109,424 Pap Tests, of which 281 (0.26%) were diagnosed as ASC-H. Tissue follow-up was available in 181 (64%) of these cases, of which 45 (25%) were negative/cervicitis, 41 (23%) were CIN 1, 36 (20%) were CIN 2 and 59 (32%) were CIN 3. Stratification by age groups showed a higher percentage of high grade (CIN 2+) lesions (65%) in the premenopausal age group as compared with high grade lesion (35%) in the postmenopausal age group, whereas negative/CIN1 biopsies were more common in postmenopausal (65%) as compared to premenopausal (44%) women. Our data support the use of colposcopy in the management of women with ASC-H on Pap Tests. However, in the older age group, prior HPV-DNA testing may be of benefit to better identify those women at risk for high grade lesions. Copyright © 2013 Wiley Periodicals, Inc.

Scalp squamous cell carcinoma in xeroderma pigmentosum.

PubMed

Awan, Basim A; Alzanbagi, Hanadi; Samargandi, Osama A; Ammar, Hossam

2014-02-01

Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving.

A case of peritoneal metastasis during treatment for hypopharyngeal squamous cell carcinoma.

PubMed

Wakasaki, Takahiro; Omori, Hirofumi; Sueyoshi, Shintaro; Rikimaru, Fumihide; Toh, Satoshi; Taguchi, Kenichi; Higaki, Yuichiro; Morita, Masaru; Masuda, Muneyuki

2016-10-18

Advanced head and neck squamous cell carcinomas frequently develop distant metastases to limited organs, including the lungs, bone, mediastinal lymph nodes, brain, and liver. Peritoneal carcinomatosis as an initial distant metastasis from hypopharyngeal squamous cell carcinoma is quite rare. A 75-year-old man diagnosed with hypopharyngeal squamous cell carcinoma and his clinical stage was determined as T2N2cM0. Notably, the right retropharyngeal lymph node surrounded more than half of the right internal carotid artery. Concomitant conformal radiation therapy was administered for the primary hypopharyngeal lesion, and the whole neck and tumor response was evaluated at this point according to our algorithm-based chemoradioselection protocol. As the tumor responses at both the primary and lymph nodes were poor, with the right retropharyngeal lymph node in particular demonstrating mild enlargement, we performed a radical surgery: pharyngolaryngectomy, bilateral neck dissection, and reconstruction of the cervical esophagus with a free jejunal flap. Then, postoperative CRT was performed. During these therapies, the patient developed a fever and mild abdominal pain, which was associated with an increased C-reactive protein level. Contrast-enhanced computed tomography from the neck to the pelvis demonstrated mild peritoneal hypertrophy and ascites with no evidence of recurrent and/or metastatic tumor formation. We initially diagnosed acute abdomen symptoms as postoperative ileus. However, cytological examination of the refractory ascites resulted in a diagnosis of peritoneal carcinomatosis. Owing to rapid disease progress, the patient died 1.5 months after abdominal symptom onset. The present case is the second reported case of head and neck squamous cell carcinoma with peritoneal carcinomatosis as an incipient distant metastasis. Therefore, peritoneal carcinomatosis should be considered a differential diagnosis when acute abdomen is noted during treatment for head and

Scalp Squamous Cell Carcinoma in Xeroderma Pigmentosum

PubMed Central

Awan, Basim A.; Alzanbagi, Hanadi; Samargandi, Osama A.; Ammar, Hossam

2014-01-01

Context: Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Case Report: Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. Conclusion: In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving. PMID:24695441

Uterine cervical cancer with brain metastasis as the initial site of presentation.

PubMed

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

[Cytogenetic characteristics of the uterine cervical epithelium in inflammatory diseases].

PubMed

Aleksieienko, O I

2011-01-01

Functional status of epithelial cells at inflammatory cervical pathologies has been studied with the use of cytogenetic method of detection of chromosome nucleolar organizer regions. The highest level of rRNA proliferation and synthesis has been detected in cylindrical epithelial cells using the indexes of compact and transitional nucleolonemic types of nucleolar organizer regions, a higher level--in squamous cells of intermediate type, and the lowest one in squamous epithelium of superficial type.

Downregulation of p16(ink4a) inhibits cell proliferation and induces G1 cell cycle arrest in cervical cancer cells.

PubMed

Zhang, Chu-Yue; Bao, Wei; Wang, Li-Hua

2014-06-01

Studies have suggested that p16(ink4a) may be a surrogate biomarker for the diagnosis of cervical cancer; however, the function of p16(ink4a) in human cervical cancer cells remains largely unknown. Therefore, in this study, we aimed to investigate the role of p16(ink4a) in human cervical cancer cells. Immunocytochemistry was used to examine invasive squamous cell carcinoma and its precancerous lesions. p16(ink4a)-siRNA was transfected into SiHa and HeLa cells to deplete its expression. The cellular levels of p16(ink4a) mRNA and protein were detected by qRT-PCR and western blot analysis. Proliferation rates were assessed by methyl thiazolyl tetrazolium (MTT) and plate colony formation assays. Cellular migration and invasion ability were assessed by a wound healing assay and Transwell assay. Cellular apoptosis and the cell cycle were measured by flow cytometry. The protein levels of retinoblastoma (Rb), phosphorylated Rb (phospho-Rb), cyclin D1 and caspase-3 were determined by western blot analysis. The results revealed that p16(ink4a) was overexpressed in the cervical cancer and precancerous lesions (P<0.05). The downregulation of p16(ink4a) in the SiHa and HeLa cells inhibited their proliferation, migration and invasion. In the SiHa cells, p16(ink4a)-siRNA also induced G1 cell cycle arrest and apoptosis. Western blot analysis revealed that the downregulation of p16(ink4a) in the SiHa cells markedly induced caspase-3 activation and decreased cyclin D1 expression. These data suggest that the overexpression of p16(ink4a) appears to be useful in monitoring cervical precancerous lesions, which supports that the hypothesis that p16(ink4a) is a surrogate biomarker for the diagnosis of cervical cancer. The therapeutic targeting of overexpressed p16(ink4a) in the p16(ink4a)-cyclin-Rb pathway may be a useful strategy in the treatment of cervical cancer.

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-13

Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

[Estrogen and progesterone receptors in normal cervix and primary cervical carcinoma].

PubMed

Shen, K; Yueng, W; Ngan, H

1994-05-01

Estrogen and progesterone receptor levels (ER and PR) were measured in 21 specimens of cervical carcinoma and in 17 normal cervix by monoclonal enzyme immunoassay (ER-EIA and PR-EIA). In normal cervix, 88.2% of specimens were ER-positive (more than 15 fmol/mg protein), 74.5% were PR-positive (more than 15 fmol/mg protein) and 74.5% were both ER and PR-positive. In cervical cancer, 66.7% of malignancies were ER-positive, 42.9% were PR-positive and 38.1% were both ER and PR-positive. There was no significant difference in ER status between the normal cervix and cervical cancer (P > 0.05), but PR status and levels in normal cervix were significantly higher than those in cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not correlated to the tumor stage, histologic grade and menopausal status. PR levels in premenopausal patients with squamous cell carcinoma were significantly higher than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P < 0.05). In addition, serum E2 level was also assayed in 21 patients with cervical cancer. There was significant difference in E2 levels between the premenopausal and postmenopausal patients (P < 0.01). Patients were stratified according to E2 levels, a significant difference in PR level and in ratio of PR/ER was noted (P < 0.05, P < 0.01).

Estrogen and progesterone receptors in normal cervix and primary cervical carcinoma.

PubMed

Shen, K; Yueng, W; Ngan, H

1994-09-01

Estrogen and progesterone receptors (ER, PR) were measured in 21 specimens of cervical cancer and in 17 specimens of normal cervix by monoclonal enzyme immunoassay (EIA). In normal cervix, 88.2% of specimens were ER-positive ( > 15 fmol/mg protein), 74.5% were PR-positive ( > 15 fmol/mg protein) and 74.5% were both ER- and PR-positive. In cervical cancer, 66.7% were ER-positive, 42.9% were PR-positive and 38.1% were both ER- and PR- positive. There was no significant difference in ER status between the normal cervix and cervical cancer (P > 0.05), but PR status and levels in normal cervix were significantly higher than those in cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not correlated to the tumor stage, histologic grade and menopausal status. PR levels in premenopausal patients with squamous cell carcinoma were significantly higher than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P < 0.05). In addition, serum E2 level was also assayed in 21 patients with cervical cancer. There was significant difference in E2 levels between the premenopausal and postmenopausal patients (P < 0.01). Patients were stratified according to E2 levels, a significant difference in PR levels and in the ratio of PR/ER was noted (P < 0.05, P < 0.01).

High-grade squamous intraepithelial lesions in pregnant and non-pregnant women.

PubMed

Xavier-Júnior, José Cândido C; Dufloth, Rozany M; do Vale, Diama B; Tavares, Thalita A; Zeferino, Luiz C

2014-04-01

To evaluate if the prevalence of cervical smear results varies between pregnant and non-pregnant women stratified by age group. Observational analytical study with a total sample of 1,336,180 pregnant and non-pregnant women, aged between 20 and 34 years, who underwent cervical cancer screening in the Primary Health Care of the national health system in the area of Campinas in Brazil during the period of 2005-2009. The source is the information system for cervical cancer screening. Data collected on abnormal cervical smears were analyzed using the Chi-square test and Fisher's exact test and the magnitude of the association between pregnancy and high-grade squamous epithelial lesions was analyzed by odds ratio (OR) and estimated values with confidence intervals (CI) of 95%. 15,190 pregnant women and 395,961 non-pregnant women were analyzed and fulfilled the inclusion criteria. Regardless of age, no statistical differences were observed for high-grade squamous intraepithelial lesion prevalence (OR 0.90; CI 0.66-1.23). Taking into account the five-year age groups, however, low-grade squamous intraepithelial lesion was less prevalent in pregnant women aged 20-24 (OR 0.71; 0.54-0.95) and 25-29 years (OR 0.56; 0.35-0.89); also, atypical squamous cells of undetermined significance was more prevalent in non-pregnant women aged 25-29 years (OR 0.72; 0.54-0.97). The study showed that the cytological prevalence of high-grade squamous intraepithelial lesion was similar in pregnant and non-pregnant women, regardless of age. The results indicate that there are no reasons for specific approaches to cervical cancer screening for pregnant women. The examination should be carried out only on pregnant women who have not been tested according to current recommendations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

PubMed

Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

Radiation Therapy and Cisplatin With or Without Triapine in Treating Patients With Newly Diagnosed Stage IB2, II, or IIIB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

ClinicalTrials.gov

2018-06-20

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vaginal Cancer AJCC v6 and v7; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified

Koilocytosis and squamous (pre)neoplasia as detected in population-based cervical screening: practice and theory.

PubMed

Boon, M E; Boon, L M; de Bosschere, M J A; Verbruggen, B S M; Kok, L P

2005-01-01

Koilocytosis (cavitation of the cytoplasm due to active HPV infection) can be detected in the screening process for cervical carcinoma. To report the practice of detection of koilocytosis and (pre)neoplasia in population screening and to exploit the collected data to propose an explanation for the relationship between HPV infection and nuclear precancerous changes. Centrally collected and stored (SBBW, Leiden, the Netherlands) data from all smears of six regional pathology laboratories (1995-2002), coded according to KOPAC (the national cervical smear coding system; S1: normal thru S9: invasive carcinoma) were accessed. Prevalences per 100,000 smears were calculated for koilocytosis and for squamous abnormalities after stratification for country of origin of screenees. The relative risk (RR) for the ethnic (age) groups was computed by dividing the prevalence of the relevant ethnic (age) group by the prevalence of all women. Surinamese women featured the highest prevalence of koilocytosis and of all squamous abnormalities. Moroccan women the lowest. The RR for koilocytosis was highest at 30 years (1.84) and lowest at 60 (0.26). RR dependence on age of S5-S9 lesions was similar. Compared to nonkoilocytotic smears, koilocytosis was 104 times more frequent in the 1,500 S4 smears, 36x more frequent in the 6,700 S2-S3 smears, and 24x more frequent in the 1,740 S5-S9 smears. In all three categories this difference is statistically significant. High prevalences for both koilocytosis and for preneoplasia were detected in Surinamese immigrants, however, it still does not exclude HPV infection as a confounder linked to sexual lifestyle. The presence of koilocytosis in cervical smears may serve to identify patients with an increased risk for cervical cancer and perhaps warrant more intensive surveillance than what is provided through five-yearly screening.

Nomenclature for very superficial squamous cell carcinoma of the skin and of the cervix: a critique in historical perspective.

PubMed

Kessler, Galen M; Ackerman, A Bernard

2006-12-01

Squamous-cell carcinoma is the most common of all cancers and it develops in diverse organs of the body, among those being the skin, lung, gastrointestinal tract, and genitourinary tract, the latter including the cervix. Unfortunately, no unanimity exists for naming very superficial squamous-cell carcinoma; it has not been designated in consistent fashion in a single organ, let alone in all of them, thereby resulting in confusion, not only in regard to terminology per se, but concerning matters conceptual, not the least of those being what appellation to apply to that condition when it is encountered histopathologically. This vexing situation is illustrated graphically in the skin by diagnoses for very superficial squamous-cell carcinoma as disparate as solar keratosis (actinic keratosis, senile keratosis), arsenical keratosis, radiation keratosis, Bowen disease, bowenoid papulosis, squamous-cell carcinoma in situ, as well as variations on the theme of "keratinocytic intraepidermal neoplasia" and "dysplasia," and in the cervix by squamous-cell carcinoma in situ, leukoplakia, cervical intraepithelial neoplasia I-III, as well as variations on the theme of "squamous dysplasia ()." What follows now is a recounting of the history of the subject under consideration here, a critique of dizzying, opaque terms and phrases given to that subject, and a proposal for rectifying what currently is a thoroughly untenable situation because the language, and the ideas expressed by it, are impenetrable to physicians and, thereby, are decidedly disadvantageous to patients. There is a need urgently for a single term for very superficial squamous-cell carcinoma in every organ of the body in which it develops, to wit, one that conveys diagnosis in such logical, lucid, comprehensible fashion that it is understandable, readily and immediately, to clinicians. In that way, physicians charged with management of patients can plan therapy rationally.

Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function

PubMed Central

Ammer, Amanda Gatesman; Kelley, Laura C.; Hayes, Karen E.; Evans, Jason V.; Lopez-Skinner, Lesly Ann; Martin, Karen H.; Frederick, Barbara; Rothschild, Brian L.; Raben, David; Elvin, Paul; Green, Tim P.; Weed, Scott A.

2010-01-01

Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in pre-clinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity. PMID:20505783

How Are Squamous and Basal Cell Skin Cancers Diagnosed?

MedlinePlus

... and Staging Tests for Basal and Squamous Cell Skin Cancers Most skin cancers are brought to a doctor’s ... Skin Cancers? More In Basal and Squamous Cell Skin Cancer About Basal and Squamous Cell Skin Cancer Causes, ...

Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

ClinicalTrials.gov

2018-05-04

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer AJCC v6 and v7; Stage IA2 Cervical Cancer AJCC v6 and v7; Stage IB1 Cervical Cancer AJCC v6 and v7

Squamous cell cancer (image)

MedlinePlus

Squamous cell cancer involves cancerous changes to the cells of the middle portion of the epidermal skin layer. It is ... malignant tumor, and is more aggressive than basal cell cancer, but still may be relatively slow-growing. It ...

Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up.

PubMed

Nagy, Viorica Magdalena; Ordeanu, Claudia; Coza, Ovidiu; Alin, Cristian Rancea; Traila, Alexandru; Todor, Nicolae

2012-11-01

The evaluation of 5-year results obtained through 2 radiochemotherapy (RCT) regimens: cisplatin (CDDP), 20 mg/m × 5 days every 21 days; and CDDP, 40 mg/m per week in locally advanced cervical carcinoma. In this single-institution prospective randomized phase 3 study, 326 patients with stage IIB to IIIB squamous cell cervical carcinoma treated from March 2003 to March 2005 were included. One hundred sixty patients (49%) had stage IIB cervical carcinoma, 103 patients (31.5%) had stage IIIA cervical carcinoma, and 63 patients (19.5%) had stage IIIB cervical carcinoma. The patients were randomly assigned to 2 therapeutic arms: 164 patients in arm A (5 days) concurrent RCT with CDDP, 20 mg/m per day, days 1 to 5 every 21 days; and 162 patients in arm B (weekly), concurrent RCT with CDDP, 40 mg/m per day weekly. All patients were treated with external beam radiotherapy on the abdominopelvic region using 15-MV x-rays and a cervical boost using the x-rays arch technique or medium-dose-rate intracavitary brachytherapy. The 5-year survival rate obtained through the 2 RCT regimens are not statistically different, even if a tendency of superiority can be observed in the 5-day arm as far as overall survival (78% in arm A vs 72% in arm B; p = 0.14) and disease-free survival (73% in arm A and 69% in arm B; p = 0.09) are concerned. Five-year local relapse-free survival was significantly superior in the 5-day CDDP arm (87%) in comparison with the weekly CDDP arm (77%); p < 0.01. In the 5-day arm, local relapse rate was twice lower, 21/164 (13%), compared with the weekly arm, 40/162 (25%); p < 0.01). Distance failures were identical in the 2 therapeutic groups: 22/164 (13%) and 21/162 (13%), respectively, which shows the superiority of arm A regarding local control. The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.

Chemoradiotherapy for esophageal squamous cell cancer.

PubMed

Sasaki, Yusuke; Kato, Ken

2016-09-01

Chemoradiotherapy has been clinically indicated for patients with resectable esophageal squamous cell carcinoma who refuse surgical resection and in locally advanced unresectable esophageal squamous cell carcinoma patients. Concurrent chemoradiotherapy prolongs survival than radiation therapy alone when given as definitive treatment. Therefore, chemoradiotherapy is recognized as the standard non-invasive treatment for patients with localized esophageal cancer who opt for non-surgical treatment. JCOG9906 showed promising outcomes for stage II/III ESCC patients. But there are some problems about chemoradiotherapy for esophageal squamous cell carcinoma. Late toxicities are sometimes lethal for patients who achieved complete response even after years. Salvage treatment for residual or recurrent disease is unestablished. Modified Radiation Therapy Oncology Group regimen at the dose of 50.4 Gy reduced late toxicities without reducing efficacy. Optimal timings and procedure of salvage surgery and endoscopic therapy is evaluated in JCOG0909. Strategy including salvage therapy after chemoradiotherapy should be considered at the time of starting the treatment. Targeted therapy has not shown adding effect for chemoradiotherapy for esophageal squamous cell carcinoma yet. New agents, such as immune checkpoint inhibitors, are expected to show synergistic effect with chemoradiotherapy for esophageal squamous cell carcinoma. Further investigation is needed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Potential targets for lung squamous cell carcinoma

Cancer.gov

Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in cervical cancer and associates with tumor growth.

PubMed

Liang, Jing; Nishi, Hirotaka; Bian, Mei-Lu; Higuma, Chinatsu; Sasaki, Toru; Ito, Hiroe; Isaka, Keiichi

2012-10-01

We found that the ubiquitin-conjugating enzyme E2-EPF mRNA is highly expressed in cervical squamous cancer relative to normal tissues and its expression levels positively correlate with clinical stage. Reduction of E2-EPF protein levels by >80% using shRNA decreases the expression levels of HIF-1α, and the proliferation, invasion and tumorigenicity of SiHa, a cervical squamous cancer cell line. E2-EPF knockdown also increases the chemosensitivity to topoisomerase I inhibitor (topotecan) and II (etoposide and doxorubicin). Our results suggest that E2-EPF is associated with the growth and aggressivity of cervical tumor cells. Targeting the E2-EPF pathway may have potential clinical applications for the treatment of cervical cancer.

Univariate and multivariate methods for chemical mapping of cervical cancer cells

NASA Astrophysics Data System (ADS)

Duraipandian, Shiyamala; Zheng, Wei; Huang, Zhiwei

2012-01-01

Visualization of cells and subcellular organelles are currently carried out using available microscopy methods such as cryoelectron microscopy, and fluorescence microscopy. These methods require external labeling using fluorescent dyes and extensive sample preparations to access the subcellular structures. However, Raman micro-spectroscopy provides a non-invasive, label-free method for imaging the cells with chemical specificity at sub-micrometer spatial resolutions. The scope of this paper is to image the biochemical/molecular distributions in cells associated with cancerous changes. Raman map data sets were acquired from the human cervical carcinoma cell lines (HeLa) after fixation under 785 nm excitation wavelength. The individual spectrum was recorded by raster-scanning the laser beam over the sample with 1μm step size and 10s exposure time. Images revealing nucleic acids, lipids and proteins (phenylalanine, amide I) were reconstructed using univariate methods. In near future, the small pixel to pixel variations will also be imaged using different multivariate methods (PCA, clustering (HCA, K-means, FCM)) to determine the main cellular constitutions. The hyper-spectral image of cell was reconstructed utilizing the spectral contrast at different pixels of the cell (due to the variation in the biochemical distribution) without using fluorescent dyes. Normal cervical squamous cells will also be imaged in order to differentiate normal and cancer cells of cervix using the biochemical changes in different grades of cancer. Based on the information obtained from the pseudo-color maps, constructed from the hyper-spectral cubes, the primary cellular constituents of normal and cervical cancer cells were identified.

Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

ClinicalTrials.gov

2016-11-14

Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

[Promoting effect of cyclin D1 overexpression on proliferation and epithelial mesenchymal transition of cervical squamous cell carcinoma SiHa cells].

PubMed

Wang, P; Liu, S; Cheng, B; Wu, X Z; Ding, S S; Xu, L; Liu, Y; Duan, L; Sun, S Z

2017-03-08

Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively. Cell growth curve was documented by MTT assay. CK7, E-cadherin, vimentin, Snail gene and protein expression in transfected cells were detected by RT-PCR and Western blot. RT-PCR was used to detect the mRNA expression of proliferation and differentiation-related genes like CDK4, CDK2, p21, p27, cyclin E, Rb, E2F, E6/E7 and Ki-67. After synchronization of cells, RT-PCR was used to detect of cyclin D1 and p21 mRNA expression at different time points of the cell cycle. Results: The G-3 cells with cyclin D1 overexpression were successfully established. The growth curve and Ki-67 mRNA expression accelerated in G-3 cells.Vimentin and Snail expression significantly increased at both gene and protein levels, while E-cadherin, CK7 gene and protein expression significantly decreased, indicating epithelial mesenchymal transitionoccurred in G-3 cells.Meanwhile, mRNA expression of cyclin D1, CDK4, CDK2, p21, p27, cyclin E, E2F and Rb increased, while E6/E7 and p16 showed no significant change. The expression trends of p21 and cyclin D1 were almost identical with fluctuation at different time points in the cell cycle. Conclusions: Overexpression of cyclin D1 induced by gene transfection promotes proliferation and epithelial mesenchymal transition in SiHa cells.The process is accompanied by up-regulation of CDK4, CDK2, p21, p27 and cyclin E genes.p21 expression increases synchronously with cyclin D1, suggesting a regulatory

[Neck lymphatic metastasis, surgical methods and prognosis in early tongue squamous cell carcinoma].

PubMed

Wang, L S; Zhou, F T; Han, C B; He, X P; Zhang, Z X

2018-02-09

Objective: To investigate the different pattern of neck lymph node metastasis, the choice of surgical methods and prognosis in early tongue squamous cell carcinoma. Methods: A total of 157 patients with early oral tongue squamous cell carcinoma were included in this study. Statistical analysis was performed to identify the pattern of lymph node metastasis, to determine the best surgical procedure and to analyze the prognosis. Results: The occurrence of cervical lymph node metastasis rate was 31%(48/157). Neck lymphatic metastasis was significantly related to tumor size ( P= 0.026) and histology differentiation type ( P= 0.022). The rate of metastasis was highest in level Ⅱ [33% (16/48)]. In level Ⅳ, the incidence of lymph node metastasis was 5%(7/157), and there was no skip metastases. The possibility of level Ⅳ metastasis was higher, when level Ⅱ ( P= 0.000) or Ⅲ ( P= 0.000) involved. The differentiation tumor recurrence, neck lymphatic metastasis and adjuvant radiotherapy were prognostic factors ( P< 0.05). Multivariate analyses revealed histology differentiation type, neck lymphatic metastases and adjuvant radiotherapy were the independent prognostic factors. Conclusions: Neck lymphatic metastasis rate is high in early tongue squamous cell carcinoma, simultaneous glossectomy and neck dissection should be performed. Level Ⅳ metastasis rate is extremely low, so supraomohyoid neck dissection is sufficient for most of the time. The histology differentiation type, neck lymphatic metastasis and adjuvant radiotherapy are independent prognostic factors.

Expression of the carbohydrate tumour marker Sialyl Lewis A, Sialyl Lewis X, Lewis Y and Thomsen-Friedenreich antigen in normal squamous epithelium of the uterine cervix, cervical dysplasia and cervical cancer.

PubMed

Engelstaedter, V; Fluegel, B; Kunze, S; Mayr, D; Friese, K; Jeschke, U; Bergauer, F

2012-04-01

The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion between tumor cells and endothelium. They are used as serum markers in diagnosis and treatment in a broad spectrum of human carcinomas, but their expression profile and role in the development of cervical cancer remains unclear. The aim of this study was to investigate the expression of SLeX, SLeA, LeY and TF in normal cervical squamous epithelium, cervical dysplasia and cervical cancer. Slides of paraffin-embedded tissue were fixed and incubated with monoclonal antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was evaluated by using a semi-quantitative score (IRS Score). We found a significant difference of SLeA expression in invasive cervical cancer compared to normal epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036). Staining for LeY showed the weakest results of the investigated markers. Significant differences were found when normal epithelium was compared to CIN I (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF, significant differences were found in normal epithelium compared to CIN I (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). This is the first study on the expression of SLeA, SLeX, LeY and TF in normal cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical cancer. Further studies and higher numbers are desirable.

Detection of squamous carcinoma cells using gold nanoparticles

NASA Astrophysics Data System (ADS)

Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

2015-03-01

The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

Histological assessment of cervical lymph node identifies patients with head and neck squamous cell carcinoma (HNSCC): who would benefit from chemoradiation after surgery?

PubMed

Wan, Xiao Chloe; Egloff, Ann Marie; Johnson, Jonas

2012-12-01

Postoperative chemoradiation (CRT) has been shown to be more effective than postoperative radiotherapy (RT) alone in high risk head and neck squamous cell carcinoma (HNSCC) patients. Multimodality therapy is associated with more treatment related-toxicity. In this study, we assessed cervical lymph node histological characteristics to detect prognostic and predictive value differences to help guide therapeutic decision making. Retrospective analysis of Cancer Registry data. HNSCC surgical patients who had tumor resection and neck dissection at our institution from 1980 to 2008 were identified (n=1510). Multivariable Cox proportional hazards regression models were developed to identify significant predictors of three outcomes: overall survival (OS), disease-specific survival (DSS), and neck disease recurrence (NDR). Hazard ratios were estimated for the number of cervical nodal metastases and presence of extracapsular spread (ECS) by adjuvant treatment after controlling for significant covariates. Increasing number of positive nodes was significantly associated with poorer outcomes in OS, DSS, and NDR models (p<0.0001, p<0.0001, p=0.0002, respectively). OS and DSS associated with adjuvant treatment (none, RT, or CRT) were modified by number of positive nodes, ECS status, and cancer site. The presence of ECS was associated with reduced OS and DSS (p=0.077, p=0.001 respectively), but not significantly associated with NDR (p=0.179). Nodal positive patients benefited from adjuvant therapy regardless of ECS status. CRT consistently conferred a survival advantage over RT across all nodal categories, although the difference was not statistically significant. We observed a consistent survival advantage with CRT over RT for patients with positive cervical nodal metastasis, although the difference was not statistically significant. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

PubMed

Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

2012-01-01

It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

PubMed

Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

2017-08-01

Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for

Mucin expression profile of benign and malignant cervical tissues and correlation with clinical-pathologic parameters.

PubMed

Kong, X; Ding, L J; Wang, Z X

2017-01-01

To detect the expression of mucins in diverse benign and malignant cervical tissues of cervical disease. 158 cases of cervical tissues were collected. Sections were stained with monoclonal antibodies against MUC1, MUC2, MIUC4, MUC5AC, and MUC20 by immunohistochemistry. Normal cervical epithelium showed high expr ession of MUC1I, MUC4, and MUC5AC, partial expression of MUC20, and no MUC2. With the development from chronic cervicitis, cervical intraepithelial neoplasia (CI7N) to cervical squamous cell carcinoma (SCC), the expression of MUC1, NMUC4, and MUC20 was statistically significant. The expression of MUCl was related with the depth of invasion and clinical stage of SCC. The positive rates of MUC4 and MUC20 were associated with the degree of differentiation and clinical stage of SCC. There was a correlation between the expression of MUC4, MUC 1, and MUC20 in cervical squamous lesions. Mucins may be involved in the development of cervical cancer.

Intensity-modulated radiotherapy for cervical node squamous cell carcinoma metastases from unknown head-and-neck primary site: M. D. Anderson Cancer Center outcomes and patterns of failure.

PubMed

Frank, Steven J; Rosenthal, David I; Petsuksiri, Janjira; Ang, K Kian; Morrison, William H; Weber, Randal S; Glisson, Bonnie S; Chao, K S Clifford; Schwartz, David L; Chronowski, Gregory M; El-Naggar, Adel K; Garden, Adam S

2010-11-15

Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and the survival rates calculated using the Kaplan-Meier method. Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon. Copyright © 2010 Elsevier Inc. All rights reserved.

Intensity-Modulated Radiotherapy for Cervical Node Squamous Cell Carcinoma Metastases From Unknown Head-and-Neck Primary Site: M. D. Anderson Cancer Center Outcomes and Patterns of Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Steven J., E-mail: sjfrank@mdanderson.or; Rosenthal, David I.; Petsuksiri, Janjira

2010-11-15

Purpose: Conventional therapy for cervical node squamous cell carcinoma metastases from an unknown primary can cause considerable toxicity owing to the volume of tissues to be irradiated. In the present study, hypothesizing that using intensity-modulated radiotherapy (IMRT) would provide effective treatment with minimal toxicity, we reviewed the outcomes and patterns of failure for head-and-neck unknown primary cancer at a single tertiary cancer center. Methods and Materials: We retrospectively reviewed the records of 52 patients who had undergone IMRT for an unknown primary at M.D. Anderson Cancer Center between 1998 and 2005. The patient and treatment characteristics were extracted and themore » survival rates calculated using the Kaplan-Meier method. Results: Of the 52 patients, 5 presented with Stage N1, 11 with Stage N2a, 23 with Stage N2b, 6 with Stage N2c, 4 with Stage N3, and 3 with Stage Nx disease. A total of 26 patients had undergone neck dissection, 13 before and 13 after IMRT; 14 patients had undergone excisional biopsy and presented for IMRT without evidence of disease. Finally, 14 patients had received systemic chemotherapy. All patients underwent IMRT to targets on both sides of the neck and pharyngeal axis. The median follow-up time for the surviving patients was 3.7 years. The 5-year actuarial rate of primary mucosal tumor control and regional control was 98% and 94%, respectively. Only 3 patients developed distant metastasis with locoregional control. The 5-year actuarial disease-free and overall survival rate was 88% and 89%, respectively. The most severe toxicity was Grade 3 dysphagia/esophageal stricture, experienced by 2 patients. Conclusion: The results of our study have shown that IMRT can produce excellent outcomes for patients who present with cervical node squamous cell carcinoma metastases from an unknown head-and-neck primary tumor. Severe late complications were uncommon.« less

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma

PubMed Central

Fan, Song; Tang, Qiong-lan; Lin, Ying-jin; Chen, Wei-liang; Li, Jin-song; Huang, Zhi-quan; Yang, Zhao-hui; Wang, You-yuan; Zhang, Da-ming; Wang, Hui-jing; Dias-Ribeiro, Eduardo; Cai, Qiang; Wang, Lei

2011-01-01

Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently. PMID:22010576

Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

PubMed Central

2010-01-01

Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

Comparison of absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissue

NASA Astrophysics Data System (ADS)

Peresunko, O. P.; Zelinska, N. V.; Prydij, O. G.; Zymnyakov, D. A.; Ushakova, O. V.

2013-12-01

We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

Long-term outcome of definitive radiotherapy for cervical esophageal squamous cell carcinoma.

PubMed

Sakanaka, Katsuyuki; Ishida, Yuichi; Fujii, Kota; Itasaka, Satoshi; Miyamoto, Shin'ichi; Horimatsu, Takahiro; Muto, Manabu; Mizowaki, Takashi

2018-01-18

The aim of this study was to identify the long-term clinical outcome of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT) for cervical esophageal squamous cell carcinoma (CESCC). We retrospectively reviewed the medical records of 30 patients with CESCC [clinical stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty-six patients underwent elective nodal irradiation for the neck node levels III, IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy. Twenty-six patients underwent concurrent chemotherapy. Initial disease progression sites, locoregional control (LRC) rate, overall survival (OS) rate, and toxicities were retrospectively evaluated. A univariate analysis was performed to identify prognostic factors. With a median follow-up of 110 months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5- and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant and both area accounted for 83%, 6% and 11% of the initial progression sites. Unresectable status and M1LYM were significantly associated with poor LRC (p < 0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in 13.3% of patients. During the follow-up, patients without any disease progression did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events, including hypothyroidism and cardiovascular disease, were observed; 5- and 10-year cumulative incidence rates of grade 2 hypothyroidism and ≥grade 3 cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively. Definitive radiotherapy yields a cure for patients with CESCC while preserving their laryngopharyngeal function. The poor LRC rate in the advanced stage needs to be overcome for a better prognosis. As the incidence

Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

ClinicalTrials.gov

2018-05-24

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7

Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amsbaugh, Mark J., E-mail: mjamsb01@louisville.edu; Yusuf, Mehran; Cash, Elizabeth

Purpose/Objective(s): To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. Methods and Materials: All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ{sup 2}, Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. Results: The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016),more » and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. Conclusions: For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC

Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status.

PubMed

Amsbaugh, Mark J; Yusuf, Mehran; Cash, Elizabeth; Silverman, Craig; Wilson, Elizabeth; Bumpous, Jeffrey; Potts, Kevin; Perez, Cesar; Bert, Robert; Redman, Rebecca; Dunlap, Neal

2016-10-01

To investigate the factors contributing to the clinical presentation of oropharyngeal squamous cell carcinoma (OPSCC) in the era of risk stratification using human papilloma virus (HPV) and smoking status. All patients with OPSCC presenting to our institutional multidisciplinary clinic from January 2009 to June 2015 were reviewed from a prospective database. The patients were grouped as being at low risk, intermediate risk, and high risk in the manner described by Ang et al. Variance in clinical presentation was examined using χ(2), Kruskal-Wallis, Mann-Whitney, and logistic regression analyses. The rates of HPV/p16 positivity (P<.001), never-smoking (P=.016), and cervical lymph node metastases (P=.023) were significantly higher for patients with OPSCC of the tonsil, base of tongue (BOT), or vallecula subsites when compared with pharyngeal wall or palate subsites. Low-risk patients with tonsil, base of tongue, or vallecula primary tumors presented with nodal stage N2a at a much higher than expected frequency (P=.007), and high-risk patients presented with tumor stage T4 at a much higher than expected frequency (P=.003). Patients with BOT primary tumors who were never-smokers were less likely to have clinically involved ipsilateral neck disease than were former smokers (odds ratio 1.8; P=.038). The distribution of cervical lymph node metastases was not associated with HPV/p16 positivity, risk group, or subsite. When these data were compared with those in historical series, no significant differences were seen in the patterns of cervical lymph node metastases for patients with OPSCC. For patients with OPSCC differences in HPV status, smoking history and anatomic subsite were associated with differences in clinical presentation but not with distribution of cervical lymph node metastases. Historical series describing the patterns of cervical lymph node metastases in patients with OPSCC remain clinically relevant. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Aspects on Oral Squamous Cell Carcinoma

PubMed Central

Markopoulos, Anastasios K

2012-01-01

Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. This article overviews the essential points of oral squamous cell carcinoma, highlighting its risk and genomic factors, the potential malignant disorders and the therapeutic approaches. It also emphasizes the importance of the early diagnosis. PMID:22930665

Correlation of DNA Ploidy with Progression of Cervical Cancer

PubMed Central

Singh, M.; Mehrotra, S.; Kalra, N.; Singh, U.; Shukla, Y.

2008-01-01

The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79), moderate (36), and severe (12) dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS)” (57) along with controls (69), in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity. PMID:20445775

Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

ClinicalTrials.gov

2016-07-30

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral

Epithelial-to-mesenchymal transition in penile squamous cell carcinoma.

PubMed

Masferrer, Emili; Ferrándiz-Pulido, Carla; Masferrer-Niubò, Magalí; Rodríguez-Rodríguez, Alfredo; Gil, Inmaculada; Pont, Antoni; Servitje, Octavi; García de Herreros, Antonio; Lloveras, Belen; García-Patos, Vicenç; Pujol, Ramon M; Toll, Agustí; Hernández-Muñoz, Inmaculada

2015-02-01

Epithelial-to-mesenchymal transition is a phenomenon in epithelial tumors that involves loss of intercellular adhesion, mesenchymal phenotype acquisition and enhanced migratory potential. While the epithelial-to-mesenchymal transition process has been extensively linked to metastatic progression of squamous cell carcinoma, studies of the role of epithelial-to-mesenchymal transition in squamous cell carcinoma containing high risk human papillomaviruses are scarce. Moreover, to our knowledge epithelial-to-mesenchymal transition involvement in human penile squamous cell carcinoma, which can arise through transforming HPV infections or independently of HPV, has not been investigated. We evaluated the presence of epithelial-to-mesenchymal transition markers and their relationship to HPV in penile squamous cell carcinoma. We assessed the expression of E-cadherin, vimentin and the epithelial-to-mesenchymal transition related transcription factors Twist, Zeb1 and Snail by immunohistochemical staining in 64 penile squamous cell carcinoma cases. HPV was detected by polymerase chain reaction amplification. Simultaneous loss of membranous E-cadherin expression and vimentin over expression were noted in 43.5% of penile squamous cell carcinoma cases. HPV was significantly associated with loss of membranous E-cadherin but not with epithelial-to-mesenchymal transition. Recurrence and mortality rates were significantly higher in cases showing epithelial-to-mesenchymal transition. Our findings indicate that in penile squamous cell carcinoma epithelial-to-mesenchymal transition is associated with poor prognosis but not with the presence of HPV. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Genomic instability in human actinic keratosis and squamous cell carcinoma

PubMed Central

Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

2011-01-01

OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

Detection of torque teno midi virus/small anellovirus (TTMDV/SAV) in chronic cervicitis and cervical tumors in Isfahan, Iran.

PubMed

Salmanizadeh, Sharareh; Bouzari, Majid; Talebi, Ardeshir

2012-02-01

Torque teno midi virus and small anellovirus (TTMDV/SAV) are members of the genus Gammatorquevirus within the family Anelloviridae. Cervical cancer is the second most prevalent cancer after breast cancer. The aim of this study was to determine the frequency of infection by these viruses in cervicitis and cervical tumors of women from Isfahan, Iran. Formalin-fixed, paraffin-embedded tissue samples from cervical cancers (n = 42) and cervicitis cases (n = 79) were subjected to nested PCR to identify TTMDV/SAV viral sequences. Of the 42 tumor cases, 22, 18 and 2 were diagnosed as adenocarcinoma, cervical intraepithelial neoplasia and squamous cell carcinoma, respectively. In total, 23 (55%) of the tumor samples were positive for TTMDV/SAV. Of the 79 cervicitis cases, 38 (48%) were also positive for TTMDV/SAV. This is the first report of TTMDV/SAV in cervicitis and cervical tumors of women.

The presence of advanced lesions and associating risk factors for advanced cervical carcinoma in patients with atypical sguamous cells of undetermined significance.

PubMed

Sun, L L; Chen, W; Fan, Y Y; Wang, M L; Wang, L N

2015-01-01

To characterize histopathological status, high-risk human papillomavirus (hr-HPV) infection status, and associated risk factors in patients with atypical squamous cells of undetermined significance (ASCUS). Cervical biopsies obtained from 130 ASCUS patients were subjected to histopathological examination and hr-HPV testing. Associations between advanced lesions and hr-HPV load or age were analyzed, and the confounding factors for high-grade cervical lesions were identified. Cervical biopsies from ASCUS patients had a wide range of pathological states, ranging from normal to invasive cervical carcinoma. High-risk HPV infection was significantly associated with advanced cervical lesions in ASCUS patients; hr-HPV infection and the number of gestations were risk factors for developing advanced cervical disease. A significant portion of ASCUS patients harbor advanced cervical lesions. The number of gestations and hr-HPV infection can increase the risk of developing advanced cervical lesions in ASCUS patients.

[Apoptosis and uterine cervical carcinogenesis].

PubMed

Yao, J; Lin, H; Song, H

2000-11-01

To investigate the possible role of apoptosis in the development of uterine cervical carcinoma. Formalin-fixed, paraffin-embedded samples from 190 patients [41 patients with severe dysplasia (SD); 37 with carcinoma in situ(CIS); 31 with microinvasive carcinoma (MIC), 40 with fran invasive large cell non-keratinizing epidermoid carcinoma (IC)], and 41 samples from normal cervical squamous epithelium (NE) were studied. The number of apoptotic cells was assessed in situ by the TDT-mediated dUTP-biotin nick end labeling (TUNEL) method. PCNA, p53 and bcl-2 were demonstrated immunohistochemically. (1) In NE, TUNEL-positive cells were found in the superficial layer and PCNA-positive cells were confined in the lamina profunda, while in cervical neoplasia these cells were irregulasly scattered throughout the cervical lesions. (2) The TUNEL staining index decreased while PCNA increased with progression of the neoplasm, showing a significant negative correlation between apoptosis and proliferation. (3) In patients with SD and CIS who had overexpression of p53 and bcl-2 proteins, the cells positively stained by TUNEL were significantly less in number than in these with negative p53 and bcl-2 expression. No such observation for PCNA expression. These results suggest that apoptosis is associated with the early process of cervical carcinogenesis and apoptosis is closely correlated with overexpression of p53 and bcl-2 proteins.

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma.

PubMed

Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Dodda Thimmasandra Ramanjanappa, Ravindra; Das, Debashish; Pandian, Ramanan; Khora, Samanta Sekhar; Kuriakose, Moni Abraham; Suresh, Amritha

2017-06-01

Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44 high /CD147 high cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous

[Glandular squamous cell carcinoma of the urinary bladder].

PubMed

Kovylina, M V; Pushkar', D Iu; Zaĭrat'iants, O V; Rasner, P I

2006-01-01

The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.

AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

PubMed

Fonseca, L M; do Carmo, M A

2000-01-01

Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

Atypical squamous and glandular cells of undetermined significance (ASCUS and AGUS) of the uterine cervix.

PubMed

Cenci, M; Vecchione, A

2000-01-01

ASCUS (Atypical Squamous Cells of Undetermined Significance) and AGUS (Atypical Glandular Cells of Undetermined Significance), or AGCUS, are two acronyms introduced in 1988 by The Bethesda System (TBS) for reporting borderline cytological changes in cervical cytology. ASCUS and AGUS categories should be subclassified. Five ASCUS subgroups were proposed: 1) ASCUS due to processing defects, 2) with "mature" cytoplasm, 3) in post-menopausal women (a--in the setting of atrophy and b--with estrogen stimulation), 4) atypical metaplasia, and 5) ASCUS with keratinized cytoplasm. AGUS subgroups may be subcategorized in endometrial or endocervical on the basis of origin. Endocervical AGUS should be further qualified, but the analysis of atypical glandular cells may be really difficult and the conclusive diagnosis is frequently "AGUS not otherwise specified". The subclassification of ASCUS and AGUS is useful for an appropriate clinical management, but pertinent patient information (such as age, date of last menstrual period, mechanical therapies, tamoxifen therapy, and others) is needed to avoid an overdiagnosis and consequently an overtreatment. In fact various subgroups require different clinical management. Therefore, an effective communication between cytopathologists and referring physicians is essential in the analysis of squamous and glandular atypias.

Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

ClinicalTrials.gov

2017-10-09

Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression.

PubMed

Walch-Rückheim, Barbara; Mavrova, Russalina; Henning, Melanie; Vicinus, Benjamin; Kim, Yoo-Jin; Bohle, Rainer Maria; Juhasz-Böss, Ingolf; Solomayer, Erich-Franz; Smola, Sigrun

2015-12-15

Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4(+)/IL17(+) cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancer-binding protein β (C/EBPβ) pathway as shown with a dominant-negative version of C/EBPβ and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPβ-dependent manner. Th17 cells may in turn maintain chronic inflammation within high-grade cervical lesions to further promote cancer progression. ©2015 American Association for Cancer Research.

CEACAM1 in Cervical Cancer and Precursor Lesions: Association With Human Papillomavirus Infection

PubMed Central

Albarran-Somoza, Benibelks; Franco-Topete, Ramon; Delgado-Rizo, Vidal; Cerda-Camacho, Felipe; Acosta-Jimenez, Lourdes; Lopez-Botet, Miguel; Daneri-Navarro, Adrian

2006-01-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an adhesion molecule expressed in a wide variety of tissues including epithelial cells, leukocytes, and tumors that may establish both homotypic and heterotypic interactions. The aim of this work was to study the protein expression pattern of CEACAM1 in cervical cancer and precursor lesions in the context of human papillomavirus (HPV) infection. We used immunohistochemistry to analyze CEACAM1 expression in formalin-fixed, paraffin-embedded cervical tissues from 15 healthy women, 15 patients with low-grade squamous intraepithelial lesions (SIL), 15 patients with high-grade SIL, and 15 patients with squamous carcinomas. HPV types were identified by PCR. CEACAM1 was either undetectable (13/15) or low (2/15) in normal cervical tissues. By contrast, CEACAM1 expression was increased in high-grade SIL (10 samples staining intermediate/high and 4 samples staining low) as compared with low-grade SIL with undetectable (n=3) or low (n= 12) expression. CEACAM1 expression was undetectable or low in cervical carcinoma. Our results suggest that CEACAM1 may be an interesting progression marker in SIL and cervical cancer, in particular due to reported immunoregulatory properties. PMID:16924126

Prevalence of Specific Types of Human Papiloma Virus in Cervical Intraepithelial Lesions and Cervical Cancer in Macedonian Women

PubMed Central

Aleksioska-Papestiev, Irena; Chibisheva, Vesna; Micevska, Megi; Dimitrov, Goran

2018-01-01

Introduction Cervical cancer is a malignancy originating in the transformation zone of the cervix, most commonly in the squamous cells. It is the fourth most common cancer in women worldwide, and the third most common cause of female cancer death. Genital human papilloma viruses (HPV) are sexually transmitted and approximately 630 milion people worldwide are infected. More than 200 genotypes, subtypes and variants have been reported, 13-15 being oncogenic type, which could be responsible for cervical intraepithelial lesions (CIN) or cancer. Aim Aim of this study was to evaluate the prevalence of this infection and to identify specific types of human papiloma virus in cervical intraepithelial lesions and cervical cancer in Macedonian women. Material and methods The study was conducted at the University Clinic for Obstetrics and Gynecology, Skopje, Macedonia, in a period of four years. The study was performed on a cohort of 1895, 18 - 73 year old patients who during primary examination had already abnormal PAP smear test. Cervical cells were collected in the lithotomy gynecological position of the patient, using endocervical cytobrush and cotton-tipped swab, and both were placed in sterile test tube with phosphate buffered saline. Samples were stored at temperature of 2 - 8 °C and Human Pappiloma Virus (HPV) genotyping was analyzed within 7 days by multiple Polymerase Chain Reaction (PCR) methods. Results The mean age of enrolled women was 40,8 years±10.36 SD(minimum of 18 and maximum 73 years. Among the patients, the presence of HPV by using PCR was detected in 40,68 % (769 patients) and was highly associated with cervical abnormalities. The prevalence of HPV was highest (82,1%) in women aged 20-years or less and it decreased with age and was lowest (19,9%) among patients older than 50 years. The prevalence of oncogenic types of the virus was higher if the cytologic diagnosis is CIN 3/Carcinoma in situ (CIS). In these patients detection of high risk HPV was in 79

Candida and squamous (pre)neoplasia of immigrants and Dutch women as established in population-based cervical screening.

PubMed

Engberts, M K; Vermeulen, C F W; Verbruggen, B S M; van Haaften, M; Boon, M E; Heintz, A P M

2006-01-01

The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.

In-vitro micro-Raman study of tissue samples for detecting cervical and ovarian cancer with 785-nm laser excitation

NASA Astrophysics Data System (ADS)

Sharma, S. K.; Kamemoto, L. E.; Misra, A. K.; Goodman, M. T.; Luk, H. W.; Killeen, J. L.

2010-04-01

We present results of in vitro micro-Raman spectroscopy of normal and cancerous cervical and ovarian tissues excited with 785 nm near-infrared (NIR) laser. Micro- Raman spectra of squamous cervical cells of both cervix and ovarian tissues show significant differences in the spectra of normal and cancerous cells. In particular, several well-defined Raman peaks in the 775-975 cm-1 region are observed in the spectra of normal cervix squamous cells but are completely missing in the spectra of invasive cervical cancer cells. In the high-frequency 2800-3100 cm-1 region it is shown that the peak area under CH stretching band is much lower than the corresponding area in the spectra of normal cells. In the case of ovarian tissues, the micro-Raman spectra show noticeable spectral differences between normal cells and ovarian serous cancer cells. In particular, we observed the accumulation of β-carotene in ovarian serous cancer cells compared to normal ovarian cells from women with no ovarian cancer. The NIR micro-Raman spectroscopy offers a potential molecular technique for detecting cervical and ovarian cancer from the respective tissues.

The role of human papillomavirus in oral squamous cell carcinoma: myth and reality.

PubMed

Kansy, Katinka; Thiele, Oliver; Freier, Kolja

2014-06-01

As the traditional risk factors for oral squamous cell carcinoma, especially tobacco, decline, new potential causative agents become the focus of research. Since the discovery of human papillomavirus (HPV) and its importance in carcinogenesis in cervical cancer, a lot of research has been undertaken to define its role in different types of cancer. In the present study, we evaluate the role of high-risk HPV types in initiation and progression of oral squamous cell carcinoma (OSCC) using a systematic review of the current literature. A literature research with the search term "HPV oral squamous cell carcinoma" was performed via PubMed. Results were screened systematically for relevance and classified into the following categories: molecular biology, genetics, clinical aspects, and prevalence. Articles were then further analyzed to assess quality. The literature research led to 527 results, with an overall HPV prevalence of 30.1 % in OSCCs. The most frequently identified subtypes were HPV-16 and HPV-18 (25.4 and 18.1 %, respectively). Prognostic relevance of HPV was discussed controversially. HPV detection via polymerase chain reaction is the most established method today. Molecular changes according to carcinogenic pathways described for cervix carcinoma were not routinely found in OSCC. In general, no definite role of high-risk HPV is currently deducible from the literature. High-risk subtypes 16 and 18 are present in the genome in approximately one third of OSCC. Its role as a causative agent is less clear than the role in oropharyngeal tumors. The infection might not be the cause of carcinogenesis in a significant number of patients but may become proportionally more important with the decrease of the classical risk factors of tobacco and alcohol.

Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank

2011-02-01

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biologicalmore » markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.« less

Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-01-08

Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

ClinicalTrials.gov

2016-04-19

Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

Is atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion clinically significant?

PubMed

McHale, Michael T; Souther, Jessica; Elkas, John C; Monk, Bradley J; Harrison, Terry A

2007-04-01

To determine the cumulative risk of cervical intraepithelial neoplasia (CIN) 2 or 3 in patients with atypical squamous cells, cannot exclude HSIL (ASC-H). A retrospective analysis was performed to identify patients referred to the dysplasia clinic with ASC-H. Initial evaluation included colposcopy, endocervical curettage, and an ectocervical biopsy, when indicated, in all the patients. A follow-up evaluation was performed at 6 and 12 months. Cumulative histological diagnosis of CIN 2 or 3 at 12 months served as the clinical end point. Two hundred twenty-nine patients with ASC-H and with a mean age of 32.8 years were evaluated. At the time of initial colposcopy, only 10.0% (23/229; 95% CI = 6.5%-15%) of the patients had histological evidence of CIN 2 or 3. The cumulative risk of CIN 2 or 3 was 12.2% (95% CI = 8%-17%). Evaluation of patients with ASC-H with colposcopy does lead to the detection of CIN 2 or 3 but perhaps at a rate lower than previously reported.

Phase II trial of Cetuximab in the Treatment of Persistent or Recurrent Squamous or Non-Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

PubMed Central

Santin, Alessandro D.; Sill, Michael W.; McMeekin, D. Scott; Leitao, Mario M.; Brown, Jubilee; Sutton, Gregory P.; Van Le, Linda; Griffin, Patricia; Boardman, Cecelia H.

2011-01-01

Purpose The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of the anti-EGFR antibody cetuximab, in persistent or recurrent carcinoma of the cervix. Patients and Methods Eligible patients had cervical cancer, measurable disease, and GOG performance status ≤2. Treatment consisted of cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 weekly until disease progression or prohibitive toxicity. The primary endpoints were progression-free survival (PFS) at 6 months and response. The study used a 2-stage group sequential design. Results Thirty-eight patients were entered with 3 exclusions, leaving 35 evaluable for analysis. Thirty-one patients (88.6%) received prior radiation as well as either 1 (n = 25, 71.4%) or 2 (n = 10) prior cytotoxic regimens. Twenty-four patients (68.6%) had a squamous cell carcinoma. Grade 3 adverse events possibly related to cetuximab included dermatologic (n = 5), GI (n = 4), anemia (n = 2), constitutional (n = 3), infection (n = 2), vascular (n = 2), pain (n = 2), and pulmonary, neurological, vomiting and metabolic (n = 1 each). No clinical responses were detected. Five patients (14.3%; two-sided 90% CI, 5.8% to 30%) survived without progression for at least 6 months. The median PFS and overall survival (OS) times were 1.97 and 6.7 months, respectively. In this study, all patients with PFS at 6 months harbored tumors with squamous cell histology. Conclusion Cetuximab is well tolerated but has limited activity in this population. Cetuximab activity may be limited to patients with squamous cell histology. PMID:21684583

Human uterine cervical epithelial cells grown on permeable support--a new model for the study of differentiation.

PubMed

Gorodeski, G I; Romero, M F; Hopfer, U; Rorke, E; Utian, W H; Eckert, R L

1994-04-01

The purpose of the present study was to establish culture conditions for human uterine cervical epithelial cells on permeable support and to determine how it affects cervical cell differentiation. Human ectocervical epithelial cells (hECE), HPV-16 immortalized hECE cells (ECE16-1) and Caski cells were grown on collagen-coated filters. Culture conditions, density of cells in culture and expression of epithelial and cervical-cell phenotypic markers were determined and compared in cells grown on filter and on solid support. Compared with the latter, cultures on filter had a higher cell density, hECE cells stratified to 5-12 cell layers compared to 1-3 on solid support, and cells of all three types expressed intercellular tight junctions. The cytokeratin profiles revealed differences between the three cell types as well as differences within the same cell species when grown on filter, compared to solid support. Of particular importance was the finding of a higher expression of K-13 in hECE grown on filter compared to solid support; K-13 is a marker of ectocervical cell differentiation. The cytokeratin profiles of the cultured hECE, ECE16-1 and Caski cells resembled those of ectocervical, squamous metaplastic and endocervical epithelia, respectively. hECE and ECE16-1 expressed involucrin protein, the level of which in both was higher in cells grown on filter compared to solid support. Polarization of the cultures was determined by morphology (stratification of hECE cells, expression of pseudomicrovilli in the apical cell membrane), selective apical vs. basolateral secretion of [35S]methionine- and [35S]cysteine-, [3H]fucose- and [14C]glucosamine-labeled molecules, and positive short-circuit current (Isc) under voltage-clamp conditions. Confluency of the cultures was determined by measuring transepithelial unidirectional fluxes of inert molecules with different molecular weights (MWs) through the paracellular pathway, and by measuring transepithelial conductance. The

[Clinical significance of σ1 receptor over-expression in cervical cancer and the effect of its synthetic ligands on the growth of cervical cancer cells].

PubMed

Deng, Y Q; Zhou, X H; Jiang, L L; Tang, X J; Zhang, Y X; Cui, J Q

2017-07-25

Objective: To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods: (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein. (2) The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3) Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results: (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC ( P= 0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P= 0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P= 0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P= 0.022]. MOS of the patients with σ1R

Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells.

PubMed

Kong, Lu; Hao, Qi; Wang, Ying; Zhou, Ping; Zou, Binbin; Zhang, Yu-xiang

2015-09-29

nc886 or VRNA2-1 has recently been identified as a noncoding RNA instead of a vault RNA or a pre-microRNA. Several studies have reported that pre-miR-886 plays a tumor-suppressive role in a wide range of cancer cells through its activity as a cellular protein kinase RNA-activated (PKR) ligand and repressor. However, by sequencing stem-PCR products, we found that a microRNA originating from this precursor, vault RNA2-1-5p (VTRNA2-1-5p), occurs in cervical cancer cells. The expression levels of the predicted targets of VTRNA2-1-5p are negatively correlated with VTRNA2-1-5p levels by quantitative reversion transcription PCR (qRT-PCR). Previous results have shown that VTRNA2-1-5p is overexpressed in human cervical squamous cell carcinomas (CSCCs) compared with adjacent healthy tissues. Inhibition of VTRNA2-1-5p increases Bax protein expression and apoptotic cell death in cervical cancer cells. Our findings suggest that VTRNA2-1-5p has oncogenic activity related to the progression of cervical cancer. Here, we report that VTRNA2-1-5p directly targeted p53 expression and functioned as an oncomir in cervical cancer. VTRNA2-1-5p inhibition decreased cervical cancer cell invasion, proliferation, and tumorigenicity while increasing apoptosis and p53 expression. Interestingly, VTRNA2-1-5p inhibition also increased cisplatin-induced apoptosis of HeLa and SiHa cells. In human clinical cervical cancer specimens, low p53 expression and high VTRNA2-1-5p expression were positively associated.In addition, VTRNA2-1-5p was found to directly target the 5' and 3' untranslated regions (UTRs) of p53. We propose that VTRNA2-1-5p is a direct regulator of p53 and suggest that it plays an essential role in the apoptosis and proliferation of cervical cancer cells.

Multiple squamous cells in thyroid fine needle aspiration: Friends or foes?

PubMed

Gage, Heather; Hubbard, Elizabeth; Nodit, Laurentia

2016-08-01

Abundant squamous cells are rarely encountered in thyroid FNA with only few case reports noted in the literature. Their presence and cytologic features may pose a diagnostic dilemma and challenges for proper classification and follow-up. We intend to gain more insight into the frequency of this finding and its clinical significance. Our electronic records were searched over 16 years to reveal 15 thyroid FNAs with abundant squamous cells. The available cytology and surgical resection slides were reviewed and radiologic records and clinical follow-up was documented. Only 15 out of 8811 thyroid FNAs from our department contained predominantly squamous cells (0.17%) of which two were interpreted as nondiagnostic, four as atypical, eight as benign, and one malignant. Surgical follow-up was available in eight cases only with benign lesions representing the majority of the cases (squamous metaplasia in Hashimoto thyroiditis, benign epidermoid/branchial cleft or thyroglossal duct cysts, and one case squamous cell carcinoma). The cases without surgical resection were stable on subsequent ultrasound studies. Thyroid aspirates with predominance of squamous cells cannot be classified in the current Bethesda categories. Even when interpreted as atypical or equivocal, the squamous cells present in our small case series were mostly benign. The only malignant case was easily identified cytologically because of its higher degree of differentiation. The most common pitfall for atypical squamous cells in these aspirates was squamous metaplasia in the setting of Hashimoto thyroiditis and degenerative changes. Diagn. Cytopathol. 2016;44:676-681. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

PubMed Central

Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

2014-01-01

Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

Outcome and cervical metastatic spread of squamous cell cancer of the buccal mucosa, a retrospective analysis of the past 25 years.

PubMed

Sagheb, Keyvan; Blatt, Sebastian; Kraft, Ina Sophie; Zimmer, Stefanie; Rahimi-Nedjat, Roman-Kia; Al-Nawas, Bilal; Walter, Christian

2017-07-01

Because of the low proportion of squamous cell carcinomas (SCCs) of the buccal mucosa within the carcinomas of the oral cavity in the Western population, data concerning metastatic pattern are sparse. Therefore, this retrospective study is focusing on the occurrence of cervical metastases (CM) and the overall outcome of this tumor entity. From January 1988 to October 2013, 113 patients were treated in the Department of Oral and Maxillofacial Surgery, Mainz, for an oral SCC of the cheek. Metastatic pattern and clinical parameters that are possibly associated with an increased risk for CM as well as overall outcome were analyzed. The average follow-up was 48 months (range: 1-248 months). A total of 55 (49%) patients were female and 58 (51%) male, with an average age of 65 ± 13 years (♀68 ± 14 years; ♂63 ± 11 years). In total, 55% of the patients either smoked and/or consumed alcohol. In total, 34% of the patients had a stage III or IV tumor, with overall 23% having CM at the time of diagnosis. During the follow-up, 50% (n = 56) of the patients developed a relapse after 12 months (median). Tumor size (P = 0.002*) and grading (P < 0.001*) are significantly associated with the occurrence of CM. Metastases (P = 0.008*) and advanced tumor size (P = 0.018) had an influence on the survival, whereas the relapse had no significant influence (P = 0.928). Five-year survival rate was 80%. SCC of the buccal mucosa shows aggressive behavior with a considerably high proportion of relapse. Since overall outcome is significantly decreased by the cervical metastatic pattern, a selective, ipsilateral neck dissection for this patient group is recommended as the primary management. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

APOBEC3A Expression in Penile Squamous Cell Carcinoma.

PubMed

Heller, Martina; Prigge, Elena-Sophie; Kaczorowski, Adam; von Knebel Doeberitz, Magnus; Hohenfellner, Markus; Duensing, Stefan

2017-11-23

APOBECs (apolipoprotein B mRNA-editing catalytic polypeptides) are cytidine deaminases that have been implicated in the host defense against viruses by blocking viral replication. They have also been shown to play a role in genome hypermutation in several human cancers. An APOBEC3 hypermutation signature has been discovered in cervical cancer, which is intimately associated with infection by high-risk human papillomaviruses (HPVs). At the same time, HPV genomes themselves are subject to DNA editing by APOBECs. Similar to cervical cancer, a proportion of penile squamous cell carcinomas (SCCs) is etiologically driven by high-risk HPVs, but very little is known about the role of APOBECs in penile SCC development and progression. A series of 34 penile SCCs was analyzed for the expression of APOBEC3A protein by immunohistochemistry. HPV genotyping was carried out using a bead-based multiplex hybridization assay preceded by BSGP5+6+ primer-based amplification. We found a frequent reduction of APOBEC3A protein expression in the invasive parts of the majority of HPV-negative penile SCCs. In contrast, the majority of HPV-positive penile SCCs retained APOBEC3A expression during malignant progression. Our results suggest that APOBEC3A expression is downregulated during progression towards invasiveness in HPV-negative penile SCC, but maintained in HPV-positive penile SCC. How high-risk HPV-infected tumor cells tolerate high APOBEC3A, which appears to exert tumor suppressive functions in HPV-negative penile SCCs, remains to be elucidated. © 2017 S. Karger AG, Basel.

Histological characteristics of human papilloma-virus-positive and-negative invasive and in situ squamous cell tumours of the penis

PubMed Central

Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C; Frisch, Morten

2009-01-01

A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from 145 patients with invasive (n = 116) or in situ (n = 29) penile squamous cell carcinoma were subjected to systematic histological evaluation and were PCR-tested for 14 hrHPV types and 23 low-risk HPV types. Around half (52%) of invasive and nine-tenths (90%) of in situ lesions were positive for an hrHPV type, of which HPV 16 was by far the predominant type (91% of hrHPV-positive lesions). In relation to histological characteristics, hrHPV positivity was statistically significantly more common in high-grade tumours, lesions dominated by small tumour cells, lesions with a high number of multinucleated cells and mitoses, and lesions with a small amount of parakeratosis. In conclusion, about half of invasive penile squamous carcinomas in this study were hrHPV-positive, most notably to HPV 16, and probably arose through in situ lesions whereas the other half of invasive penile lesions appeared to be unrelated to hrHPV. A number of histological characteristics differed significantly between hrHPV-positive and -negative invasive penile carcinomas. PMID:19335557

Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

PubMed

Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

2017-07-01

Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was

Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2015-04-29

Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

Expression of Cat Podoplanin in Feline Squamous Cell Carcinomas.

PubMed

Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

2017-12-01

Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis. Until now, we have established several mAbs against podoplanin in humans, mice, rats, rabbits, dogs, cattle, and cats. We have reported podoplanin expression in canine melanoma and squamous cell carcinomas using an anti-dog podoplanin mAb PMab-38. In this study, we investigated podoplanin expression in 40 feline squamous cell carcinomas (14 cases of mouth floor, 13 of skin, 9 of ear, and 4 of tongue) by immunohistochemical analysis using an anti-cat podoplanin mAb PMab-52, which we recently developed by cell-based immunization and screening (CBIS) method. Of the total 40 cases, 38 (95%) showed positive staining for PMab-52. In particular, 12 cases (30%) showed a strong membrane-staining pattern of squamous cell carcinoma cells. PMab-52 can be useful for antibody therapy against feline podoplanin-expressing squamous cell carcinomas.

Basaloid and warty carcinomas of the vulva. Distinctive types of squamous cell carcinoma frequently associated with human papillomaviruses.

PubMed

Kurman, R J; Toki, T; Schiffman, M H

1993-02-01

In a previous study, we described an elevated prevalence of human papillomavirus (HPV) in two specific types of squamous cell carcinoma of the vulva designated basaloid carcinoma (BC) and warty carcinoma (WC) compared with the conventional type of keratinizing squamous cell carcinoma (KSC). To determine whether there were other differences in their clinical presentation or behavior, we examined 100 cases of squamous cell carcinoma of the vulva classified as BC (28 cases), WC (seven cases), and KSC (65 cases). We included only cases in which tissue adjacent to the tumor was present so that the presence of intraepithelial lesions (squamous hyperplasia, lichen sclerosus, and vulvar intraepithelial neoplasia [VIN]) could be correlated with the different types of invasive carcinomas. Microscopically, BC was characterized by a relatively uniform population of small, ovoid cells with a high nuclear-cytoplasmic ratio resembling VIN 3. Although WC was similar to typical squamous cell carcinoma, it contained many squamous cells that displayed marked nuclear pleomorphism, enlargement, atypia, and multinucleation in conjunction with cytoplasmic cavitation resembling koilocytotic atypia in intraepithelial lesions. The majority of the women with BC and WC were less than 60 years of age, and the proportion of black women was higher as compared with the women with KSC, the majority of whom were white and over 65 years of age. On crude comparison, women with BC appeared to have a survival advantage compared with women with KSC; however, through multivariate modelling, when all possible confounding variables were taken into account, there was little residual impression of a survival advantage of women with BC compared with those having KSC. Substantial differences were found among the three types of carcinoma with regard to the prevalence of adjacent intraepithelial lesions. Squamous hyperplasia was found adjacent to KSC in 54 (83%) of the 65 cases, whereas 27 (77%) of 35 cases of

Human papillomavirus (HPV) oncoprotein E6 facilitates Calcineurin-Nuclear factor for activated T cells 2 (NFAT2) signaling to promote cellular proliferation in cervical cell carcinoma.

PubMed

Ram, Babul Moni; Dolpady, Jayashree; Kulkarni, Rakesh; Usha, R; Bhoria, Usha; Poli, Usha Rani; Islam, Mojahidul; Trehanpati, Nirupma; Ramakrishna, Gayatri

2018-01-01

The calcineurin-NFAT signaling pathway regulates cell proliferation, differentiation, and development in diverse cell types and organ systems. Deregulation of calcineurin-NFAT signaling has been reported in leukaemias and few solid tumors such as breast and colon. In the present study, we found elevated calcineurin protein levels and phosphatase activity in cervical cancer cell lines and depletion of the same attenuated cell proliferation. Additionally, nuclear levels of NFAT2, a downstream target of calcineurin, viz, was found elevated in human papillomavirus (HPV) infected cells, HeLa and SiHa, compared to the HPV negative cells, HaCaT and C33A, indicative of its higher DNA binding activity. The nuclear levels of both NFAT1 and NFAT3 remain unaltered implicating they have little role in cervical carcinogenesis. Similar to the in vitro studies, the HPV infected human squamous cell carcinoma specimens showed higher NFAT2 levels compared to the normal cervical epithelium. Depletion of NFAT2 by RNAi attenuated growth of SiHa cells. Overexpression of HPV16 oncoproteins viz, E6 and E7 increased NFAT2 expression levels and DNA binding activity, while knockdown of E6 by RNAi decreased the same. Briefly, we now report an activation of calcineurin-NFAT2 axis in cervical cancer and a novel role of HPV oncoprotein in facilitating NFAT2 dependent cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Atypical Squamous Cells of Undetermined Significance: Bethesda Classification and Association with Human Papillomavirus

PubMed Central

Barcelos, Ana Cristina Macêdo; Michelin, Márcia Antoniazi; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

2011-01-01

Introduction. To analyze patients with atypical squamous cells of undetermined significance (ASCUS) through a cytology review and the presence of microbiological agents, with consideration of colposcopy and semiannual tracking. Methods. 103 women with ASCUS were reviewed and reclassified: normal/inflammatory, ASCUS, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). If ASCUS confirmed, it was subclassified in reactive or neoplastic ASCUS, ASC-US, or ASC-H; and Regione Emilia Romagna Screening Protocol. Patients underwent a colposcopic examination, and test for Candida sp., bacterial vaginosis, Trichomonas vaginalis, and human papillomavirus (HPV) were performed. Results. Upon review, ASCUS was diagnosis in 70/103 (67.9%), being 38 (54.2%) reactive ASCUS and 32 (45.71%) neoplastic ASCUS; 62 (88.5%) ASC-US and 8 (11.41%) ASC-H. ASCUS (Regione Protocol), respectively 1-5: 15 (21.4%), 19 (27.1%), 3 (27.1%), 16 (22.8%), and 1 (1.4%). A higher number of cases of cervical intraepithelial neoplasia (CIN) II/III in the biopsies of patients with ASC-H compared to ASC-US (P = .0021). High-risk HPV test and presence of CIN II/III are more frequent in ASC-H than ASC-US (P = .031). Conclusions. ASC-H is associated with clinically significant disease. High-risk HPV-positive status in the triage for colposcopy of patients with ASC-US is associated with increased of CIN. PMID:21760701

Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.

PubMed

Obata, Kyoichi; Shimo, Tsuyoshi; Okui, Tatsuo; Matsumoto, Kenichi; Takada, Hiroyuki; Takabatake, Kiyofumi; Kunisada, Yuki; Ibaragi, Soichiro; Yoshioka, Norie; Kishimoto, Koji; Nagatsuka, Hitoshi; Sasaki, Akira

2017-11-01

The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Combined Influence of Oral Contraceptives and Human Papillomavirus Virus on Cutaneous Squamous Cell Carcinoma

PubMed Central

Efird, Jimmy T.; Toland, Amanda E.; Lea, C. Suzanne; Phillips, Christopher J.

2011-01-01

The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV β-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway. PMID:21499554

Regeneration of cervical reserve cell-like cells from human induced pluripotent stem cells (iPSCs): A new approach to finding targets for cervical cancer stem cell treatment.

PubMed

Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2017-06-20

Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer.

PubMed

Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei

2017-01-01

The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Cervical cytology of atypical squamous cells, cannot exclude high-grade squamous intra-epithelial lesion: significance of age, human papillomavirus DNA detection and previous abnormal cytology on follow-up outcomes.

PubMed

Sung, Chang Ohk; Oh, Young Lyun; Song, Sang Yong

2011-11-01

Despite the usefulness of Pap tests for cancer screening, outcomes can be difficult to predict when atypical squamous cells (ASCs) are identified. According to the 2001 Bethesda system, ASCs can be subdivided into two groups: ASCs of undetermined significance (ASC-US); and ASCs, cannot exclude high-grade squamous intra-epithelial lesion (ASC-H). ASC-H interpretations are uncommon, and studies involving this type of lesion are based on small numbers of cases. Cross-sectional, retrospective study of 392 ASC-H cases. The follow-up outcomes of ASC-H cases that were diagnosed during routine primary screening between 2002 and 2008 were investigated, and relationships between clinicopathological parameters were assessed, particularly positive test for high-risk HPV (HPV) DNA, patient age at diagnosis and previous abnormal cytology. Of the 392 cases, high-grade squamous intra-epithelial lesion (HSIL) was detected in 111 (28.3%) cases, squamous cell carcinoma was detected in 15 (3.8%) cases, low-grade squamous intra-epithelial lesion was detected in 37 (9.4%) cases, reactive change was detected in 178 (45.4%) cases, atrophy was detected in 47 (12.0%) cases, and adenocarcinoma was detected in four (1.0%) cases. The prevalence of HSIL or greater was 27.8% for women aged ≥ 40 years, and 52.3% for women aged <40 years (p<0.001). HPV positivity in ASC-H smears was significantly associated with HSIL or greater, irrespective of age (<40 years, p=0.003; ≥ 40 years, p<0.001). ASC-H with previous abnormal cytology greater than ASC-US showed a significantly higher detection rate for HSIL or greater at follow-up (p<0.001). Patient age, positive HPV DNA test and previous abnormal cytology are useful predictors of underlying HSIL or greater in women with ASC-H. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Nature of "basal" and "reserve" cells in oviductal and cervical epithelium in man.

PubMed Central

Peters, W M

1986-01-01

The epithelium of the human fallopian tube (oviduct) and cervix were studied by histological, immunohistological, and ultrastructural methods with a view to establishing the nature of the so called "basal" and "reserve" cells. The results indicated that the "basal" cells of the oviductal epithelia were T lymphocytes, with a predominance of T cytotoxic and suppressor cells. A more heterogeneous inflammatory cell population was present in cervical epithelium, although once again T cytotoxic and suppressor cells were the most numerous subtype. The intraepithelial inflammatory cells were quite distinct from the cells commonly referred to as "reserve" cells (reserve cell hyperplasia), which have epithelial characteristics. The origin of the "reserve" cells is unclear, but they seem to arise within the epithelium. They probably represent an early sign of squamous metaplasia. The lymphoid tissue of fallopian tube and endocervix shows similarities with that of the endometrium and mucosal associated lymphoid tissue in general. Images PMID:2937810

Performance of the cobas HPV Test for the Triage of Atypical Squamous Cells of Undetermined Significance Cytology in Cervical Specimens Collected in SurePath.

PubMed

Tewari, Devansu; Novak-Weekley, Susan; Hong, Christina; Aslam, Shagufta; Behrens, Catherine M

2017-11-02

Determine performance of the cobas human papillomavirus (HPV) test for triage of atypical squamous cells of undetermined significance (ASC-US) in SurePath. Women presenting for routine screening had cervical specimens collected in SurePath and specimen transport medium (STM); those with ASC-US cytology underwent colposcopy. Performance of cobas HPV in SurePath specimens that had undergone a preanalytic procedure to reverse possible cross-linking of HPV DNA was compared with Hybrid Capture 2 (hc2) specimens in STM. Among 856 women, HPV prevalence was 45.8%; HPV 16 and HPV 18 prevalences were lower than expected in the 21- to 29-year-old group in this highly vaccinated population. cobas HPV performance in SurePath was comparable to hc2 in STM. Sensitivity and specificity for detection of cervical intraepithelial neoplasia grade 3 or worse were 87.5% (95% confidence interval [CI], 71.9%-95.2%) and 55.5% (95% CI, 52.1%-58.9%) for cobas and 85.3% (95% CI, 69.9%-93.6%) and 54.7% (95% CI, 51.4%-57.9%) for hc2. Sensitivity was negatively affected by random biopsies performed at colposcopy; comparable sensitivities were achieved in the nonvaccinated and vaccinated populations with disease determined by directed biopsy only. Performance of cobas HPV for ASC-US triage in pretreated SurePath specimens meets criteria for validation. Preliminary data indicate reliable performance of HPV testing in a highly vaccinated population. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

PubMed

Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

2016-04-01

We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-02-08

Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck

Squamous cell carcinoma of the anal sacs in three dogs.

PubMed

Mellett, S; Verganti, S; Murphy, S; Bowlt, K

2015-03-01

Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass. © 2014 British Small Animal Veterinary Association.

Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia.

PubMed

Sabol, Ivan; Milutin Gašperov, Nina; Matovina, Mihaela; Božinović, Ksenija; Grubišić, Goran; Fistonić, Ivan; Belci, Dragan; Alemany, Laia; Džebro, Sonja; Dominis, Mara; Šekerija, Mario; Tous, Sara; de Sanjosé, Silvia; Grce, Magdalena

2017-01-01

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18-24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

PubMed

Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

2007-08-01

To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital.

PubMed

Heng, Suttichai; Sirichaisutdhikorn, Daranee

2016-01-01

To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.

SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

PubMed Central

Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

2016-01-01

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and

Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group.

PubMed

2000-03-01

Human papillomavirus (HPV) infections appear to be central to the development of cervical cancer. This study addresses the question of whether testing women who have low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix for HPV DNA is useful as a triage strategy. Four clinical centers in different areas of the United States participated in a randomized clinical trial of the use of HPV DNA testing in women with cytologic evidence of atypical squamous cells of undetermined significance (ASCUS) or LSIL. The study sample in this article consists only of women who had LSIL at enrollment. Within 6 months of an LSIL diagnosis (based on a Pap smear read by a community-based cytopathologist), women who were 18 years of age or older completed a standardized questionnaire and underwent a pelvic examination that included collection of cervical specimens for HPV DNA testing by Hybrid Capture II (HCII)(R) assay. Among the 642 women referred with LSIL who had analyzable test results, the mean chronologic age and age at first coitus were similar among the four clinical centers, despite the centers' ethnic and geographic diversity. Overall, HPV DNA was detected in cervical samples from 532 (82.9%) of the 642 women (95% confidence interval = 79.7%-85.7%). This high frequency of HPV positivity was confirmed by polymerase chain reaction (PCR) assays in a subset of 210 paired specimens tested by HCII and PCR (81.4% were positive by both methods). Because a very high percentage of women with an LSIL diagnosis from Pap smears are positive for HPV DNA by HCII testing, there is limited potential for this assay to direct decisions about the clinical management of women with LSIL. The role of HPV testing in the management of women with ASCUS is still under study.

[Nomenclature of squamous cell precursor lesions of the lower female genital tract : Current aspects].

PubMed

Horn, L-C; Brambs, C E; Handzel, R; Mehlhorn, G; Schmidt, D; Schierle, K

2016-11-01

The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations. In the current World Health Organization (WHO) classification a novel grading system for squamous cell precancerous lesions of the lower female genital tract has been proposed, differentiating low grade squamous intraepithelial lesions (L-SIL) including condyloma and HPV-associated alterations plus VIN 1, vaginal intraepithelial neoplasia (VaIN 1) and cervical intraepithelial neoplasia (CIN 1) from high grade squamous intraepithelial lesions (H-SIL) with VIN 2 and 3, VaIN 2 and 3 as well as CIN 2 and 3. The use of p16 immunohistochemistry can assist the differentiation. The new binary classification, however, contradicts the German cytological nomenclature (Munich nomenclature III), which differentiated three grades of dysplasia in order to avoid overtreatment of patients with moderate IN. The individual nomenclatures are compared to each other. It is recommended to report the grade of precancerous lesions in addition to the SIL classification of the WHO.

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting.

PubMed

Adhya, A K; Mahesha, V; Srinivasan, R; Nijhawan, R; Rajwanshi, A; Suri, V; Dhaliwal, L K

2009-12-01

To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001. A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out. AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old (P = 0.010). The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.

Squamous Cell Cancer of The Lung with Synchronous Renal Cell Carcinoma

PubMed Central

Ateş, İhsan; Yazıcı, Ozan; Ateş, Hale; Yazılıtaş, Doğan; Özcan, Ayşe Naz; Ağaçkıran, Yetkin; Zengin, Nurullah

2016-01-01

Coexistence of two or more primary cancers is a relatively rare case. Not with standing that the coexistence of multiple primary cancers is often discussed in the literature, there is a small number of publications concerning the coexistence of squamous cell lung carcinoma and renal cancer. In this case report, detection of both squamous cell lung carcinoma and primary renal cancer in one male patient is going to be discussed. PMID:29404140

RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

PubMed

Zhang, Jinyao; Chen, Zhaoli; Tang, Zefang; Huang, Jianbing; Hu, Xueda; He, Jie

2017-07-01

In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

Purtscher-like retinopathy associated with squamous cell carcinoma of the cervix.

PubMed

Ting, Darren Shu Jeng; Smith, Jonathan; Talks, Stephen James

2018-02-01

To describe a previously unreported case of Purtscher-like retinopathy secondary to severe acute renal failure associated with squamous cell carcinoma of the cervix. This is a case report. A 31-year-old female presented with a week history of acute abdominal pain, vomiting and severe renal failure followed by a sudden onset of bilateral visual loss. Vision was hand movement in either eye with central scotoma. Ophthalmic examination demonstrated bilateral retinal thickening and whitening with intraretinal hemorrhages localized to the peripapillary area, consistent with the diagnosis of Purtscher-like retinopathy. Further systemic examination revealed bilateral hydronephrosis secondary to underlying undiagnosed cervical carcinoma. Patient was treated with a short course of high-dose steroids. At 2 months, patient vision remained poor despite the resolution of retinal edema and hemorrhages. This case serves as the first report of Purtscher-like retinopathy secondary to acute renal failure associated with cervical carcinoma, expanding the list of causes of Purtscher's or Purtscher-like retinopathies. In the presence of significant uremia and absence of previously known association, the authors postulate that the sudden surge of uremia causes increase of endothelin-1 (a potent vasoconstrictor), resulting in downstream endothelin-induced vasculopathy with subsequent occlusion of the pre-capillary arteriolar network.

Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-01-23

Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Cervical cancer in north-eastern Libya: 2000-2008.

PubMed

Ben Khaial, F; Bodalal, Z; Elramli, A; Elkhwsky, F; Eltaguri, A; Bendardaf, R

2014-08-01

Libya is a country with a low population, listed under the EMRO. Using registers and patient records from a major primary oncology clinic, data was gathered from Libyan cervical cancer patients and various parameters were studied across 9 years. Out of 4,090 female cancer cases during the study period, 1.8% were cervical cancer (n = 74). The average age of presentation was 53 years, with most of the cases (60%, n = 44) being premenopausal. Approximately 65% (n = 48) of cervical cancer patients are diagnosed at later stages (i.e. stages III and IV). The majority of these cases are squamous cell carcinoma (83.8%, n = 62), while 16.2% (n = 12) were found to be adenocarcinoma. Patients with squamous cell carcinoma presented at later stages more often than those with adenocarcinoma. Human papilloma virus was strongly implicated in cervical cancer, with 94% (n = 63) of those who were tested being positive for HPV-16 (82.5%, n = 52) and HPV-18 (12.7%, n = 8). Diagnosis was most frequently made through biopsy (97.3%, n = 72) as opposed to Pap smears (2.7%, n = 2). Most Libyan patients were put through chemotherapy (75%, n = 55) and triple therapy (surgery with combined chemotherapy and radiotherapy) was the most common (38%, n = 28) modality of treatment. Comparisons were made between Libya and other nations, either in the developed world or neighbouring countries. The major problem of cervical cancer in Libya is delayed presentation and hence, all the recommendations focus on increased awareness for the populace, implementation of a national cancer control plan and a national screening programme.

Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma.

PubMed

Chen, Xiangyun; Wu, Jingjing; Chen, Yitian; Ye, Dongxia; Lei, Hu; Xu, Hanzhang; Yang, Li; Wu, Yingli; Gu, Wenli

2016-10-01

Ubiquitin-specific protease 14, a deubiquitinating enzyme, has been implicated in the tumorigenesis and progression of several cancers, but its role in oral squamous cell carcinoma remains to be elucidated. The aim of this study was to explore the expression pattern and roles of Ubiquitin-specific protease 14 in the occurrence and development of oral squamous cell carcinoma. Interestingly, Ubiquitin-specific protease 14 was overexpressed in oral cancer tissues and cell lines at both mRNA and protein levels. b-AP15, a specific inhibitor of Ubiquitin-specific protease 14, significantly inhibited the growth of cancer cells and increased cell apoptosis in a dose-dependent manner. Moreover, knockdown of Ubiquitin-specific protease 14 by shRNA significantly inhibited the proliferation and migration of cancer cells in vitro. Finally, using a xenograft mouse model of oral squamous cell carcinoma, knockdown of Ubiquitin-specific protease 14 markedly inhibited tumor growth and triggered the cancer cell apoptosis in vivo, supporting previous results. In conclusion, for the first time we have demonstrated the expression pattern of Ubiquitin-specific protease 14 in oral squamous cell carcinoma and verified a relationship with tumor growth and metastasis. These results may highlight new therapeutic strategies for tumor treatment, application of Ubiquitin-specific protease 14 selective inhibitor, such as b-AP15, or knockdown by shRNA. Collectively, Ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes

PubMed Central

Piroozmand, Ahmad; Mostafavi Zadeh, Seyed Mostafa; Madani, Azita; Soleimani, Reza; Nedaeinia, Reza; Niakan, Mohammad; Avan, Amir; Manian, Mostafa; Moradi, Mohammad; Eftekhar, Zahra

2016-01-01

Background Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. Objectives The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. Materials and Methods Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. Results The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. Conclusions Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID:27279992

Towards improving cervical cancer screening in Nigeria: a review of the basics of cervical neoplasm and cytology.

PubMed

Dim, C C

2012-01-01

Cervical cancer screening is the key to reducing the incidence and mortality of cervical cancer in developing countries. In the absence of a national screening program, healthcare givers in Nigeria are encouraged to routinely inform and screen eligible women. This review aims at equipping health workers for this task by re-educating them on the basics of the disease and its screening by cytology. Relevant texts and online databases including Pubmed, African Journal Online, and Google Scholar, were searched for relevant literature on the subject area. Persistent infection by a high-risk human papilloma virus, especially types 16 and 18, is necessary for the development of cervical cancer. The exfoliation of cells from the metaplastic squamous cells of transformation zone of the cervix is the basis of cervical cytology. Organized Pap screening reduces the incidence and mortality of cervical cancer, but screening protocols vary. Nevertheless, annual screening is not recommended except for high-risk women such as HIV-positive women. Abnormal Pap smear results are currently reported using either the Bethesda System or the British Society for Clinical Cytology classification, and colposcopy with or without biopsy are necessary when indicated. In conclusion, the use of cervical cytology to detect pre-cancerous lesions followed by an appropriate treatment when necessary is the key to reducing invasive cervical cancer. The task of provider-initiated counseling and testing for cervical cancer by health practitioners requires update on the current etio-pathology of cervical cancer, and its screening as reviewed.

Cutaneous and laryngeal squamous cell carcinoma in mixed epidermolysis bullosa, kindler syndrome.

PubMed

Mizutani, Hiromi; Masuda, Koji; Nakamura, Naomi; Takenaka, Hideya; Tsuruta, Daisuke; Katoh, Norito

2012-05-01

Kindler syndrome is a rare autosomal recessive genodermatosis characterized by trauma-induced acral blisters in infancy and childhood, photosensitivity, and progressive poikiloderma. Other clinical features include chronic erosive gingivitis, dysphagia, esophageal and urethral strictures, ectropion, and an increased risk of mucocutaneous squamous cell carcinoma. We describe a patient with Kindler syndrome associated with squamous cell carcinoma of the skin and larynx. He had squamous cell carcinoma on his left knee with simultaneous unresectable laryngeal carcinoma at the age of 43 years. The squamous cell carcinoma on his knee was excised and the laryngeal carcinoma was treated with radiation therapy. Although pathophysiology of Kindler syndrome and its frequency of association with cancer are still not fully elucidated, we speculate that long-term erosion and regeneration of mucosal and cutaneous surfaces may have induced squamous cell carcinoma on the patient's knee and larynx.

Nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro.

PubMed

Wang, Chengze; Gu, Weiting; Zhang, Yunpeng; Ji, Yawen; Wen, Yong; Xu, Xin

2017-07-05

Cigarette smoking is one of highly risk factors of cervical cancer. Recently nicotine has been reported to increase proliferation and invasion in some smoking related cancers, like non-small cell lung cancer and esophageal squamous cell cancer. However, the effects and mechanisms of nicotine stimulation on cervical cancer cells are not clear. Here, we investigated the effects and mechanisms of nicotine stimulation on HeLa cells in vitro. In our study, we found that nicotine could accelerate HeLa cells migration and invasion, activate PI3K/Akt and NF-κB pathways and increase the expression of Vimentin in vitro. Moreover, we demonstrated that the specific PI3K inhibitor LY294002 could reverse nicotine-induced cell migration and invasion, NF-κB activation and up-regulation of Vimentin. Inhibition of NF-κB by Pyrrolidine dithiocarbamate (PDTC) also antagonized nicotine-induced cell migration, invasion and up-regulation of Vimentin. Simply put, these findings suggest that nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro. Copyright © 2017 Elsevier GmbH. All rights reserved.

Molecular Mechanisms of Ethanol-associated Oro-esophageal Squamous Cell Carcinoma

PubMed Central

Liu, Yao; Chen, Hao; Sun, Zheng; Chen, Xiaoxin

2016-01-01

Alcohol drinking is a major etiological factor of oro-esophageal squamous cell carcinoma (OESCC). Both local and systemic effects of ethanol may promote carcinogenesis, especially among chronic alcoholics. However, molecular mechanisms of ethanol-associated OESCC are still not well understood. In this review, we summarize current understandings and propose three mechanisms of ethanol-associated OESCC: (1) Disturbance of systemic metabolism of nutrients: during ethanol metabolism in the liver, systemic metabolism of retinoids, zinc, iron and methyl groups is altered. These nutrients are known to be associated with the development of OESCC. (2) Disturbance of redox metabolism in squamous epithelial cells: when ethanol is metabolized in oro-esophageal squamous epithelial cells, reactive oxygen species are generated and produce oxidative damage. Meanwhile, ethanol may also disturb fatty-acid metabolism in these cells. (3) Disturbance of signaling pathways in squamous epithelial cells: due to its physico-chemical properties, ethanol changes cell membrane fluidity and shape, and may thus impact multiple signaling pathways. Advanced molecular techniques in genomics, epigenomics, metabolomics and microbiomics will help us elucidate how ethanol promotes OESCC. PMID:25766659

Urothelial cells in smears from cervix uteri

PubMed Central

Palaoro, Luis Alberto; Guerra, Fernando; Angeleri, Anabela; Palamas, Marta; Melba, Sardi-Segovia; Rocher, Adriana Esther

2012-01-01

Objectives: To establish the cytological criteria to identify the urothelial cells in cervical smears in order to avoid mistakes in the cytological diagnosis. Materials and Methods: Cervical smears from 34 post menopausal women with vesicovaginal fistulas, advanced bladder prolapse and genital erosive lichen planes (vulvar kraurosis) (Group 1) and transitional cell metaplasia of the cervix (TCM, Group 2) were stained with Papanicolaou technique. The cervical samples were taken during the routine annual examination for prevention of the uterine cancer. Results: The smears of cervix from Group 1 showed urothelial cells from the three layers of the transitional epithelium. The umbrella cells are the bigger ones with relatively large nuclei. Frequently, they are multinucleated with single or multiple nucleoli and a typical “frothy” cytoplasm (cytoplasmic vacuoles). The cells of the Group 2 showed nuclei with oval to spindled shapes, some tapered ends, less cytoplasm than squamous metaplastic cells, powdery chromatin, small nucleoli and nuclear grooves. Conclusions: The umbrella cells may be mistaken for dysplastic cells originating in low grade squamous intraepithelial lesions lesions (LSILs) due to their nuclear and cytoplasm sizes. Therefore, it is important to know the possibility of their appearance in the cervical smears, especially in post menopausal patients in order to avoid a false diagnosis of an intraepithelial lesion. It is unlikely that deeper cells of urothelium would be confused with high grade squamous intraepithelial lesion (HSIL) cells. However, their presence might be a reason of mistake in the diagnosis. TCM is an under-recognized metaplastic phenomenon of the cervix and vagina, which is a mimicker of high-grade squamous intraepithelial lesion. The differential characteristic between umbrella cells, cells from TCM and the deeper urothelial cells, and LSIL and HSIL are detailed in the present paper. PMID:22438615

NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

PubMed

Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

2016-08-01

Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL.

PubMed

Halliwell, Diane E; Morais, Camilo L M; Lima, Kássio M G; Trevisan, Julio; Siggel-King, Michele R F; Craig, Tim; Ingham, James; Martin, David S; Heys, Kelly A; Kyrgiou, Maria; Mitra, Anita; Paraskevaidis, Evangelos; Theophilou, Georgios; Martin-Hirsch, Pierre L; Cricenti, Antonio; Luce, Marco; Weightman, Peter; Martin, Francis L

2016-07-12

Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 μm to 30 μm due to the optical diffraction limit.

Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL

PubMed Central

Halliwell, Diane E.; Morais, Camilo L. M.; Lima, Kássio M. G.; Trevisan, Julio; Siggel-King, Michele R. F.; Craig, Tim; Ingham, James; Martin, David S.; Heys, Kelly A.; Kyrgiou, Maria; Mitra, Anita; Paraskevaidis, Evangelos; Theophilou, Georgios; Martin-Hirsch, Pierre L.; Cricenti, Antonio; Luce, Marco; Weightman, Peter; Martin, Francis L.

2016-01-01

Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (≥0.2 μm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 μm to 30 μm due to the optical diffraction limit. PMID:27406404

Cytological analysis of atypical squamous epithelial cells of undetermined significance using the world wide web.

PubMed

Washiya, Kiyotada; Abe, Ichinosuke; Ambo, Junichi; Iwai, Muneo; Okusawa, Estuko; Asanuma, Kyousuke; Watanabe, Jun

2011-01-01

The low-level consistency of the cytodiagnosis of uterine cervical atypical squamous epithelial cells of undetermined significance (ASC-US) employing the Bethesda System has been reported, suggesting the necessity of a wide survey. We presented cases judged as ASC-US on the Web and analyzed the voting results to investigate ASC-US cytologically. Cytology samples from 129 patients diagnosed with ASC-US were used. Images of several atypical cells observed in these cases were presented on the Web. The study, based on the voting results, was presented and opinions were exchanged at the meeting of the Japanese Society of Clinical Cytology. The final diagnosis of ASC-US was benign lesions in 76 cases and low- and high-grade squamous intraepithelial lesions in 44, but no definite diagnosis could be made for the remaining 9. The total number of votes was 17,884 with a 36.5% consistency of cases judged as ASC-US. Benign cases were divided into 6 categories. Four categories not corresponding to the features of koilocytosis and small abnormal keratinized cells were judged as negative for an intraepithelial lesion or malignancy at a high rate. A Web-based survey would be useful which could be viewed at any time and thereby facilitate the sharing of cases to increase consistency. Copyright © 2011 S. Karger AG, Basel.

Cervical cancer biopsy reporting: a review.

PubMed

Reyes, Maria Carolina; Cooper, Kumarasen

2014-01-01

The terminology for reporting human papillomavirus-associated squamous lesions in the cervix, both in tissue samples and cytology specimens, has suffered from many changes throughout the last years creating confusion in interpreting cervical biopsy and cytology reports by clinicians. This review presents a summary and discussion of the current terminology for reporting results of cervical biopsies and cytology with emphasis in the lower anogenital squamous terminology consensus recommendations for tissue specimens and the 2001 Bethesda Workshop for reporting cytology results. Microscopic features of cervical lesions in tissue samples and cytology specimens are presented. Biomarkers, including p16 and Ki-67, are discussed and how they can help the pathologist when dealing with difficult cases.

Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

ClinicalTrials.gov

2012-10-30

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: cytohistologic correlation study with diagnostic pitfalls.

PubMed

Mokhtar, Ghadeer A; Delatour, Nicolas L D Roustan; Assiri, Ali H; Gilliatt, M Angela; Senterman, Mary; Islam, Shahidul

2008-01-01

In the current study, we explore the diagnostic parameters and pitfalls in the follow-up of 123 cases of Pap smears diagnosed as high-grade atypical squamous cells (ASC-H) at our institution. A computer database search was performed from the archives of the Ottawa Hospital Cytopathology Service for cases diagnosed with ASC-H between January 2003 and July 2005. Follow-up of the 123 cases of ASC-H showed high grade squamous intraepithelial lesion (HSIL) in 73 patients (59.4%), low grade squamous intraepithelial lesion (LSIL) in 11 (8.9%), immature squamous metaplasia in 23 (18.7%), reactive squamous cell changes in 12 (9.8%), benign glandular lesions (endocervical atypia, degenerated glandular cells) in 2 (1.6%) and atrophy in 2 (1.6%). In our study, 83 patients were younger than 40 years (67.4%), with biopsy-proven HSIL found in 54 patients (65.1%). The remaining 40 patients (32.6%) were older than 40 years of age, and follow-up biopsies showed HSIL in 19 patients (47.5%). In our study, 59.4% of the cases that were diagnosed cytologically as ASC-H were found to have HSIL on subsequent biopsies. This correlation was stronger in patients below the age of 40 years (65.1% vs. 47.5%). The cytopathologic feature most strongly associated with HSIL was the presence of coarse nuclear chromatin (84%).

Corneal squamous cell carcinoma in a Border Collie.

PubMed

Busse, Claudia; Sansom, Jane; Dubielzig, R R; Hayes, Alison

2008-01-01

A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.

Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

PubMed

Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

2016-11-04

Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines.

PubMed

Tanaka, Kyoko; Miyazawa, Masaki; Mikami, Mikio; Aoki, Daisuke; Kiguchi, Kazushige; Iwamori, Masao

2016-10-01

Monoclonal antibody YHD-06 generated by immunization with GM2 reacted with gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, among which GalNAc-GD1a was characterized as an antigen of autoimmune peripheral neuropathies including Guillain-Barré syndrome. When glycolipids were examined by TLC-immunostaining with YHD-06 in seven human cervical carcinoma-derived cell lines, GM2 was found in all cell lines, amounting to 15.5 % to 57.5 % of total gangliosides. Whereas GalNAc-GD1a was present in three cell lines, amounting to 5.4-17.5 % of total gangliosides, and GalNAc-GM1b in four cell lines in amounts of less than 2 %. The elevated amounts of gangliosides with GM2 determinant were closely correlated with the relative intensities of gene expression of GalNAc transferase, this being characteristic of cervical carcinoma-derived cells. However, in tissues from patients with several histological types of cervical carcinomas, GM3 was ubiquitously expressed in amounts of more than 66 % of total gangliosides, GM2 was expressed in only five of 15 tissues, and both GalNAc-GM1b and GalNAc-GD1a were not even detected in trace amounts. Since GM1 was detected in all tissues in amounts of less than 0.06 μg/mg dried tissue, all cervical carcinoma tissues were revealed to exhibit GM2 synthesis, indicating that enhanced synthesis of gangliosides with GM2 determinant is a characteristic of cultivated cells in vitro. Similarly, although I(3)SO3-GalCer was not present in the squamous cell carcinoma (SCC) tissues, SCC-derived cells selectively expressed II(3)SO3-LacCer. Since enhanced synthesis of GM2 has been reported in SV-40 virus-transfected fibroblasts, papilloma virus might be involved in the expression of GM2 in cervical carcinoma-derived cells.

Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-19

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

ClinicalTrials.gov

2013-12-10

Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral

The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone.

PubMed

Wang, Mei; Wu, Chunping; Guo, Yu; Cao, Xiaojuan; Zheng, Wenwei; Fan, Guo-Kang

2017-05-01

Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti-chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no

Breast implant capsule-associated squamous cell carcinoma: a report of 2 cases.

PubMed

Olsen, Daniel L; Keeney, Gary L; Chen, Beiyun; Visscher, Daniel W; Carter, Jodi M

2017-09-01

The use of prosthetic implants for breast augmentation has become commonplace. Although implants do not increase the risk of conventional mammary carcinoma, they are rarely associated with anaplastic large cell lymphoma. We report 2 cases of breast implant capsule-associated squamous cell carcinoma with poor clinical outcomes. Both patients (56-year-old woman and 81-year-old woman) had long-standing implants (>25 years) and presented with acute unilateral breast enlargement. In both cases, squamous cell carcinoma arose in (focally dysplastic) squamous epithelium-lined breast implant capsules and widely invaded surrounding breast parenchyma or chest wall. Neither patient had evidence of a primary mammary carcinoma or squamous cell carcinoma at any other anatomic site. Within 1 year, one patient developed extensive, treatment-refractory, locoregional soft tissue metastasis, and the second patient developed hepatic and soft tissue metastases and died of disease. There are 2 prior reported cases of implant-associated squamous cell carcinoma in the plastic surgery literature; one provides no pathologic staging or outcome information, and the second case was a capsule-confined squamous cell carcinoma. Together, all 4 cases share notable commonalities: the patients had long-standing breast implants and presented with acute unilateral breast pain and enlargement secondary to tumors arising on the posterior aspect of squamous epithelialized implant capsules. Because of both its rarity and its unusual clinical presentation, implant capsule-associated squamous cell carcinoma may be underrecognized. The aggressive behavior of the tumors in this series underscores the importance of excluding malignancy in patients with long-standing breast implants who present with acute unilateral breast pain and enlargement. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of mast cells in oral squamous cell carcinoma

PubMed Central

Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

2017-01-01

The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. PMID:28435394

FOXF2 promoter methylation is associated with prognosis in esophageal squamous cell carcinoma.

PubMed

Chen, Xiaoying; Hu, Haochang; Liu, Jing; Yang, Yong; Liu, Guili; Ying, Xiuru; Chen, Yingmin; Li, Bin; Ye, Cong; Wu, Dongping; Duan, Shiwei

2017-02-01

Esophageal squamous cell carcinoma is a commonly malignant tumor of digestive tract with poor prognosis. Previous studies suggested that forkhead box F2 ( FOXF2) could be a candidate gene for assessing and predicting the prognosis of human cancers. However, the relationship between FOXF2 promoter methylation and the prognosis of esophageal squamous cell carcinoma remained unclear. Formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma tissues of 135 esophageal squamous cell carcinoma patients were detected for FOXF2 promoter methylation status by methylation-specific polymerase chain reaction approach. DNA methylation results were evaluated with regard to clinicopathological features and overall survival. Our study confirmed that FOXF2 promoter hypermethylation could independently predict a poorer overall survival of esophageal squamous cell carcinoma patients ( p = 0.002), which was consistent with the data mining results of the data from 82 esophageal squamous cell carcinoma patients in The Cancer Genome Atlas datasets ( p = 0.036). In addition, no correlation was found between FOXF2 promoter methylation and other clinic pathological parameters (age, gender, differentiation, lymph node metastasis, stage, cutting edge, vascular invasion, smoking behavior, and drinking history). In conclusion, FOXF2 methylation might be a useful prognostic biomarker for esophageal squamous cell carcinoma patients.

Generation of K14-E7/∆N87βcat double transgenic mice as a model of cervical cancer.

PubMed

Bulut, Gülay; Üren, Aykut

2015-01-01

Nearly all cervical cancers are initiated by a subset of high-risk human papilloma viruses (HPVs). However, cervical cancers develop only in a small fraction of women who are infected with these viruses. HPV is required, but not sufficient for developing cervical cancer. Activation of complementary signaling pathways appears to be necessary for malignant transformation of cervical epithelial cells that are immortalized by HPV. Here, we describe the creation and maintenance of a double transgenic mouse model that is based on constitutively active Wnt/β-catenin signaling in cervical epithelial cells expressing the HPV oncoprotein E7. These mice develop invasive cervical squamous carcinomas within 6 months with an average penetrance of 94 %.

Loss in 3p and 4p and gain of 3q are concomitant aberrations in squamous cell carcinoma of the vulva.

PubMed

Jee, K J; Kim, Y T; Kim, K R; Kim, H S; Yan, A; Knuutila, S

2001-05-01

Neoplasm of the vulva is a rare malignancy accounting for <5% of all female genital-tract cancer. However, in recent years the incidence of vulva intraepithelial neoplasia, known to serve as a precursor to carcinoma, has increased in young women generating considerable interest in its pathogenesis. Genetic changes at the molecular level in precursor or invasive vulvar tumors are not well investigated, and DNA copy number changes have not been reported until now. We used comparative genomic hybridization (CGH) to analyze genetic alterations in 10 primary invasive squamous cell carcinomas of the vulva. Chromosomal aberrations were identified in 8/10 cases. The most frequent chromosomal losses were 4p13-pter (five cases), 3p (four cases), and 5q (two cases), and less frequent losses were detected at 6q, 11q, and 13q (one case each). The most frequent chromosomal gains were 3q (four cases) and 8p (three cases), and less frequent gains were found in 9p, 14, 17, and 20q (one case each). The pattern of chromosomal imbalance in vulvar cancer detected by CGH was revealed to be very similar to that in cervical cancers, despite regional differences in their prevalence. These results suggest that the pathogenic pathways in vulvar and cervical carcinomas may be similar and that the genetic background may be common to these two squamous cell carcinomas.

Histopathology of Cervical Cancer and Arsenic Concentration in Well Water: An Ecological Analysis.

PubMed

Mostafa, Mohammad Golam; Queen, Zarat Jahin; Cherry, Nicola

2017-10-06

Arsenic in drinking water is causally linked with cancer of the skin, lung, and urinary bladder, but there is very little data on a possible role for arsenic in the etiology of cervical cancer, a disease in which human papilloma virus is held to be a necessary but not sufficient cause. All histopathology results from cervical specimens from the National Institute of Cancer Research and Hospital (NICRH), Dhaka (1997-2015), and the Anowara Medical Services (2003-2015), both serving the whole of Bangladesh, were classified by cell type. Arsenic concentrations in well water in the thana of residence were estimated from systematic sampling carried out by the British Geological Survey. In a case-referent analysis arsenic estimates for cases of cervical cancer were compared with those found to have benign lesions. In this study, 3464 NICRH (CH) cervical specimens and 30,050 community medical service (CMS) specimens were available: 3329 (CH) and 899 (CMS) were recorded as malignant. Most were squamous cell carcinoma, of which 4.9% were poorly differentiated. Overall, there was no increase in cervical cancer with increasing arsenic concentration. Among those with squamous cell histology, a strong dose response was seen for poorly differentiated cancer with increasing arsenic exposure. The odds ratio increased monotonically, compared with exposure <10 μg/L, from 1.58 at 10 < 50 μg/L to 8.11 at >200 μg/L (p < 0.001). Given the high proportion of Bangladeshis using drinking water containing >50 μg/L of arsenic, the evidence that arsenic is implicated in cancer grade suggests a need for further investigation and the introduction of cervical screening in high arsenic areas.

SUZ12 is a novel putative oncogene promoting tumorigenesis in head and neck squamous cell carcinoma.

PubMed

Wu, Yaping; Hu, Huijun; Zhang, Wei; Li, Zhongwu; Diao, Pengfei; Wang, Dongmiao; Zhang, Wei; Wang, Yanling; Yang, Jianrong; Cheng, Jie

2018-04-18

The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC patient cohorts. Moreover, SUZ12 protein was markedly up-regulated in primary HNSCC samples from our patient cohort as assessed by immunohistochemical staining and its overexpression significantly associated with cervical node metastasis and reduced overall and disease-free survival. In the 4-nitroquinoline 1-oxide (4NQO)-induced HNSCC mouse model, increased SUZ12 immunostaining was observed along with disease progression from epithelial hyperplasia to squamous cell carcinoma in tongue. Furthermore, shRNA-mediated SUZ12 knock-down significantly inhibited cell proliferation, migration and invasion in HNSCC cells, and resulted in compromised tumour growth in vivo. Collectively, our data reveal that SUZ12 might serve as a putative oncogene by promoting cell proliferation, migration and invasion, and also a novel biomarker with diagnostic and prognostic significance for HNSCC. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Wild-type p53 reactivation by small-molecule Minnelide™ in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma.

PubMed

Caicedo-Granados, Emiro; Lin, Rui; Fujisawa, Caitlin; Yueh, Bevan; Sangwan, Veena; Saluja, Ashok

2014-12-01

The incidence of high-risk human papillomavirus (HR-HPV) head and neck squamous cell carcinoma (HNSCC) continues to increase, particularly oropharyngeal squamous cell carcinoma (OPSCC) cases. The inactivation of the p53 tumor suppressor gene promotes a chain of molecular events, including cell cycle progression and apoptosis resistance. Reactivation of wild-type p53 function is an intriguing therapeutic strategy. The aim of this study was to investigate whether a novel compound derived from diterpene triepoxide (Minnelide™) can reactivate wild-type p53 function in HPV-positive HNSCC. For all of our in vitro experiments, we used 2 HPV-positive HNSCC cell lines, University of Michigan squamous cell carcinoma (UM-SCC) 47 and 93-VU-147, and 2 HPV-positive human cervical cancer cell lines, SiHa and CaSki. Cells were treated with different concentrations of triptolide and analyzed for p53 activation. Mice bearing UM-SCC 47 subcutaneous xenografts and HPV-positive patient-derived tumor xenografts were treated with Minnelide and evaluated for tumor growth and p53 activation. In HPV-positive HNSCC, Minnelide reactivated p53 by suppressing E6 oncoprotein. Activation of apoptosis followed, both in vitro and in vivo. In 2 preclinical HNSCC animal models (a subcutaneous xenograft model and a patient-derived tumor xenograft model), Minnelide reactivated p53 function and significantly decreased tumor progression and tumor volume. Triptolide and Minnelide caused cell death in vitro and in vivo in HPV-positive HNSCC by reactivating wild-type p53 and thus inducing apoptosis. In addition, in 2 HPV-positive HNSCC animal models, Minnelide decreased tumor progression and induced apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical and biological significance of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma.

PubMed

Lu, Chunlai; Xu, Fengkai; Gu, Jie; Yuan, Yunfeng; Zhao, Guangyin; Yu, Xiaofang; Ge, Di

2015-08-01

Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma. Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4(+) cells (CD133(+)CXCR4(+) and CD133(-)CXCR4(+)) showed high invasive potential and CD133(+)CXCR4(+) cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival (P < .01). Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review.

PubMed

Guma, Sergei; Maglantay, Remegio; Lau, Ryan; Wieczorek, Rosemary; Melamed, Jonathan; Deng, Fang-Ming; Zhou, Ming; Makarov, Danil; Lee, Peng; Pincus, Matthew R; Pei, Zhi-Heng

2016-01-01

The human papilloma virus (HPV) is a carcinogen known for its strong association with cervical cancers and cervical lesions. It is also known to be associated with a variety of squamous cell carcinomas in other areas, such as the penis, vulva, anus and head and neck. However, the association with urothelial carcinoma remains controversial. Here, we report a case of urothelial carcinoma with squamous differentiation associated with HPV-6/HPV-11. This is a case of a 70 year old man who presented with nocturia and pressure during urination. During the TURP procedure for what was clinically thought to be benign prostate hyperplasia with pathologic diagnosis as prostate carcinoma, a 2 cm papillary mass was found in the distal penile urethra. The papillary mass was found to be a high grade urothelial carcinoma positive for GATA 3 expression, with focal areas of squamous differentiation. The areas with squamous differentiation demonstrated koilocytic differentiation, which were positive for strong p16 expression. The tumor was found to harbor low risk HPV 6/11 by in situ hybridization. This study case demonstrates HPV infection with a low risk subtype (HPV 6/11) associated with an urothelial carcinoma with squamous differentiation and condylomatous features.

MRI-Based Texture Analysis to Differentiate Sinonasal Squamous Cell Carcinoma from Inverted Papilloma.

PubMed

Ramkumar, S; Ranjbar, S; Ning, S; Lal, D; Zwart, C M; Wood, C P; Weindling, S M; Wu, T; Mitchell, J R; Li, J; Hoxworth, J M

2017-05-01

Because sinonasal inverted papilloma can harbor squamous cell carcinoma, differentiating these tumors is relevant. The objectives of this study were to determine whether MR imaging-based texture analysis can accurately classify cases of noncoexistent squamous cell carcinoma and inverted papilloma and to compare this classification performance with neuroradiologists' review. Adult patients who had inverted papilloma or squamous cell carcinoma resected were eligible (coexistent inverted papilloma and squamous cell carcinoma were excluded). Inclusion required tumor size of >1.5 cm and preoperative MR imaging with axial T1, axial T2, and axial T1 postcontrast sequences. Five well-established texture analysis algorithms were applied to an ROI from the largest tumor cross-section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. On the basis of 3 separate blinded reviews of the ROI, isolated tumor, and entire images, 2 neuroradiologists predicted tumor type in consensus. The inverted papilloma ( n = 24) and squamous cell carcinoma ( n = 22) cohorts were matched for age and sex, while squamous cell carcinoma tumor volume was larger ( P = .001). The best classification model achieved similar accuracies for training (17 squamous cell carcinomas, 16 inverted papillomas) and validation (7 squamous cell carcinomas, 6 inverted papillomas) datasets of 90.9% and 84.6%, respectively ( P = .537). For the combined training and validation cohorts, the machine-learning accuracy (89.1%) was better than that of the neuroradiologists' ROI review (56.5%, P = .0004) but not significantly different from the neuroradiologists' review of the tumors (73.9%, P = .060) or entire images (87.0%, P = .748). MR imaging-based texture analysis has the potential to differentiate squamous cell carcinoma from inverted papilloma and may, in the future, provide incremental information to the

Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma.

PubMed

Castaldi, P; Leccisotti, L; Bussu, F; Miccichè, F; Rufini, V

2013-02-01

The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of (18)F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of (18)F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of (18)F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of (18)F-FDG.

Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

PubMed

Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

2016-02-05

Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma.

PubMed

Li, Rong; Leng, Ai-Min; Liu, Xiao-Ming; Hu, Ting-Zi; Zhang, Lin-Fang; Li, Ming; Jiang, Xiao-Xia; Zhou, Yan-Wu; Xu, Can-Xia

2017-06-01

PTOV1 has been demonstrated to play an extensive role in many types of cancers. This study takes the first step to clarify the potential relationship between esophageal squamous cell carcinoma and PTOV1 expression and highlight the link between PTOV1 and the tumorigenesis, progression, and prognosis of esophageal squamous cell carcinoma. PTOV1 expression was detected by quantitative reverse transcription polymerase chain reaction and western blotting or immunohistochemical staining in esophageal squamous cell carcinoma cell lines, esophageal squamous cell carcinoma tissues, and its paired adjacent non-cancerous tissues. Moreover, we have analyzed the relationship between PTOV1 expression and clinicopathological features of esophageal squamous cell carcinoma. Survival analysis and Cox regression analysis were used to assess its prognostic significance. We found that PTOV1 expression was significantly higher in the esophageal squamous cell carcinoma cell lines and tissues at messenger RNA level (p < 0.001) and protein level (p < 0.001). Gender, tumor size, or differentiation was tightly associated with the PTOV1 expression. Lymph node involvement (p < 0.001) and TNM stage (p < 0.001) promoted a high PTOV1 expression. A prognostic significance of PTOV1 was also found by Log-rank method, and the overexpression of PTOV1 was related to a shorter OS and DFS. Multiple Cox regression analysis indicated overexpressed PTOV1 as an independent indicator for adverse prognosis. In conclusion, this study takes the lead to demonstrate that the overexpressed PTOV1 plays a vital role in the tumorigenesis and progression of esophageal squamous cell carcinoma, and it is potentially a valuable prognostic predicator and new chemotherapeutic target for esophageal squamous cell carcinoma.

HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status.

PubMed

Richardson, Lyndsay Ann; El-Zein, Mariam; Ramanakumar, Agnihotram V; Ratnam, Samuel; Sangwa-Lugoma, Ghislain; Longatto-Filho, Adhemar; Cardoso, Marly Augusto; Coutlée, Francois; Franco, Eduardo L

2015-12-01

Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. © 2015 American Cancer Society.

Population-based prevalence of abnormal cervical cytology findings and local risk factors in Ibadan, Nigeria: implications for cervical cancer control programs and human papilloma virus immunization.

PubMed

Thomas, J O; Ojemakinde, K O; Ajayi, I O; Omigbodun, A O; Fawole, O I; Oladepo, O

2012-01-01

To investigate the prevalence of abnormal cervical cytological findings and local risk factors in Ibadan, Nigeria. All women aged ≥15 years in each household in Idikan, Ibadan, were invited to participate in a population-based study. Structured questionnaires were administered to all consenting women. Conventional cervical Papanicolaou smears obtained from sexually active women were classified using the 2001 Bethesda system. The diagnoses were correlated with sociodemographic data and risk factors. Of 2,870 women aged ≥15 years estimated to live in Idikan, 1,204 sexually active women consented to pelvic examination and cervical smears. Results were available for 1,104 women (mean age: 39.8 years). Mean ages at menarche, first sexual intercourse and first pregnancy were 16.1, 20.3 and 20.7 years, respectively. Cytological results were categorized into atypical squamous cells of undetermined significance and atypical glandular cells 22 (1.99%); low-grade 43 (3.89%) and high-grade squamous intraepithelial lesions (HSIL) 17 (1.54%); invasive cancer 2 (0.18%) and normal 593 (53.8%) and reactive changes 427 (38.7%). The prevalence of epithelial abnormalities is 7.6%. Significant host-related factors in those with HSIL and invasive cancer included older age (mean 56.2 years), high parity and gravidity, lack of formal education and being divorced (p < 0.05). This study provides prevalence data and local risk factors for abnormal cervical cytology in a Nigerian population, which will be useful for planning future cervical cancer control programs. Copyright © 2012 S. Karger AG, Basel.

[Suppression of VEGF protein expression by arctigenin in oral squamous cell carcinoma].

PubMed

Pu, Guang-rui; Liu, Fa-yu; Wang, Bo

2015-08-01

To observe arctigenin's inhibitory effect on oral squamous cell carcinoma, and explore the possible mechanism. The expression of VEGF in 32 cases of oral squamous cell cancer and 20 adjacent tissue specimen were detected with immunohistochemistry. Human nude mouse transplantation tumor model of oral squamous cell cancer was prepared with HSC-3 cells line. Transplanted tumor growth and VEGF expression in transplanted tumor tissues were assayed after treatment with arctigenin. One-way ANOVA was used for comparison between groups with SPSS 16.0 software package. Compared with the adjacent tissue, immunohistochemical staining score of VEGF was significantly higher (P<0.01) in oral squamous cell carcinoma tissues. After treatment with arctigenin, the growth of oral squamous cell transplanted tumors in nude mouse was inhibited (P<0.05), and decreased weight in end point of observation was noted (P<0.05). There were significant differences between high dose group and low dose group (P<0.05). Compared with the nude mouse model group, the optical density of VEGF staining was significantly lower in arctigenin group (P<0.05). There were significant differences between high dose group and low dose group (P<0.05). Arctigenin can dose-dependently inhibit the growth of oral squamous cell carcinomas, and this effect may be related to down regulation of VEGF expression.

Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells

PubMed Central

Fekrazad, Reza; Hakimiha, Neda; Farokhi, Enice; Rasaee, Mohammad Javad; Ardestani, Mehdi Shafiee; Kalhori, Katayoun AM; Sheikholeslami, Farzaneh

2011-01-01

Background Worldwide, oral squamous cell carcinoma (potentially mediated by HER2) is recognized as the most commonly occurring malignant neoplasm of the oral cavity. Anti-HER2 nanobodies conjugated to gold-silica nanoshells and used as photothermal treatment for oral squamous cell carcinoma may provide a novel therapeutic alternative to current treatment for this disease. Methods KB epithelial or HeLaS3 cell cultures (controls) were exposed to these immunonanoshells, and plasmon resonance electron initiation specific to gold was employed to burn the tumor cells. Results Following this treatment, significant cell death occurred in the KB tumor cell cultures while there was no evidence of cellular damage or death in the HeLaS3 cell cultures. Conclusion These findings suggest that photothermal treatment of oral squamous cell carcinoma has considerable advantages. PMID:22131825

Treatment of oral squamous cell carcinoma using anti-HER2 immunonanoshells.

PubMed

Fekrazad, Reza; Hakimiha, Neda; Farokhi, Enice; Rasaee, Mohammad Javad; Ardestani, Mehdi Shafiee; Kalhori, Katayoun A M; Sheikholeslami, Farzaneh

2011-01-01

Worldwide, oral squamous cell carcinoma (potentially mediated by HER2) is recognized as the most commonly occurring malignant neoplasm of the oral cavity. Anti-HER2 nanobodies conjugated to gold-silica nanoshells and used as photothermal treatment for oral squamous cell carcinoma may provide a novel therapeutic alternative to current treatment for this disease. KB epithelial or HeLaS3 cell cultures (controls) were exposed to these immunonanoshells, and plasmon resonance electron initiation specific to gold was employed to burn the tumor cells. Following this treatment, significant cell death occurred in the KB tumor cell cultures while there was no evidence of cellular damage or death in the HeLaS3 cell cultures. These findings suggest that photothermal treatment of oral squamous cell carcinoma has considerable advantages.

Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells

PubMed Central

Alonso-Lecue, Pilar; de Pedro, Isabel; Coulon, Vincent; Molinuevo, Rut; Lorz, Corina; Segrelles, Carmen; Ceballos, Laura; López-Aventín, Daniel; García-Valtuille, Ana; Bernal, José M; Mazorra, Francisco; Pujol, Ramón M; Paramio, Jesús; Ramón Sanz, J; Freije, Ana; Toll, Agustí; Gandarillas, Alberto

2017-01-01

Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy. PMID:28661481

Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moy, R.L.; Eliezri, Y.D.; Bennett, R.G.

1989-05-12

Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. Themore » high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.« less

[Why does the prevalence of cytopathological results of cervical cancer screening can vary significantly between two regions of Brazil?].

PubMed

Discacciati, Michelle Garcia; Barboza, Bárbara Maria Santos; Zeferino, Luiz Carlos

2014-05-01

To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Maceió and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System. Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Maceió. In Rio de Janeiro, examination at one and two year intervals predominated, while in Maceió examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Maceió were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Maceió and that of rejected samples for analysis was five times higher in Maceió when compared to Rio de Janeiro. The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Maceió. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.

Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2018-05-22

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

[Inveterate squamous cell carcinoma of the upper eyelid: a case report].

PubMed

Rinaldi, S; Marcasciano, M; Pacitti, F; Toscani, M; Tarallo, M; Fino, P; Scuderi, G L

2013-01-01

Squamous cell carcinoma (SCC) is a malignant tumor of epithelium that shows squamous cell differentiation. It is the second most common cancer of the skin and usually occurs in areas exposed to the sun but it can rarely arise within the conjunctival epithelium with a deep component. We describe a woman with a history of chronic blepharoconjunctivitis unresponsive to topical medications. Examination disclosed a hyperaemic translucent patch with blurred margins of the upper palpebral conjunctiva. Tarsoconjunctival biopsy revealed intraepithelial squamous cell carcinoma. Management consisted of complete tumor excision with removal of the entire posterior lamella of the left upper eyelid and reconstruction. Histopathologic analysis confirmed primary squamous cell carcinoma arising from conjunctival epithelium, involving the underlying tarsus. Patients with unexplained chronic unilateral blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule out neoplasia, even when there is no sign of an evident mass.

Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-02-02

Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

Introduction of liquid-based cytology and human papillomavirus testing in cervical cancer screening in Luxembourg.

PubMed

Latsuzbaia, Ardashel; Hebette, Gaëtan; Fischer, Marc; Arbyn, Marc; Weyers, Steven; Vielh, Philippe; Schmitt, Fernando; Mossong, Joël

2017-05-01

In 2014, liquid-based cytology with HPV triage replaced conventional cytology. The aim of our study was to compare conventional and liquid-based cytology (LBC), estimate the prevalence of abnormal cervical cytology and high risk HPV (hrHPV) infection and their correlation, among screened women in Luxembourg. Between the first January 2013 and 31st December 2015, 315,868 cervical samples from 150,815 women (mean age 42.2 years) were investigated by the national cytology laboratory. Slides were prepared and screened according to European Guidelines. All cytological results were classified according to the Bethesda 2001 system terminology. The prevalence of abnormal cervical lesions was as follows: atypical squamous cells of undetermined significance (ASC-US), 1.3%; low-grade squamous intraepithelial lesion (LSIL), 1.9%; high-grade squamous intraepithelial lesion (HSIL), 0.4%. The detection rate of cytological lesions was significantly higher with LBC than with conventional cytology. Based on 11,838 samples with concomitant cytology and HPV testing, hrHPV was detected in 9.5, 45.3, 70.0, and 92.6% of women with negative cytology, ASC-US, LSIL, and HSIL, respectively. More cervical lesions were identified using LBC compared to conventional cytology. HrHPV infection was correlated with the severity of intraepithelial lesions. The current findings provide important information to evaluate the prevention of cervical cancer in Luxembourg and for monitoring the future impact of HPV vaccination. Diagn. Cytopathol. 2017;45:384-390. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Squamous cell carcinoma arising in Hailey-Hailey disease of the vulva.

PubMed

Cockayne, S E; Rassl, D M; Thomas, S E

2000-03-01

A 61-year-old woman, who was known to have Hailey-Hailey disease, presented with increasing vulval soreness. Biopsy showed vulval intraepithelial neoplasia (VIN) 3 and subsequent histology from a vulvectomy specimen showed extensive VIN with early invasive squamous cell carcinoma. This may be another example of chronic inflammation of the vulval area leading to the development of squamous cell carcinoma. However, in this case, chronic human papillomavirus may also have played a part, leading to VIN and reactivation of the Hailey-Hailey disease. We can find no previous reports of squamous cell carcinoma developing in the setting of Hailey-Hailey disease.

Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

ClinicalTrials.gov

2018-04-23

Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Mucosal human papillomavirus types in squamous cell carcinomas of the uterine cervix and subsequently on fingers.

PubMed

Forslund, O; Nordin, P; Hansson, B G

2000-06-01

Human papillomavirus (HPV), especially type 16, is causally involved in the pathogenesis of anogenital cancer. There is an increasing number of reports of HPV infections in squamous cell carcinoma (SCC) of the fingers. A search of the Swedish cancer register covering the period 1958-94 inclusive for women with a history of genital and upper extremity SCC revealed 63 cases. Archival material from both cervical and cutaneous lesions was traced and analysed for the presence of HPV DNA in 32 of these patients. A newly developed 'neighbour primer' polymerase chain reaction (PCR) for HPV 16 DNA, aimed at overcoming the obstacle of cross-linked target DNA, was shown to be superior to conventional general and type-specific HPV PCR tests. HPV DNA was significantly more frequently found in digital tumours than in tumours at other cutaneous sites of the upper extremities [67% (10 of 15) vs. 7% (three of 43); P < 0.001]. Among 13 patients with a history of both cervical and finger SCC, HPV 16 was found in cervical samples from seven patients. From five of these seven patients, HPV 16 was also present in the corresponding finger lesions. The results support the hypothesis of a possible transmission of patients' genital HPV infections to fingers.

mTOR as a Molecular Target in HPV-Associated Oral and Cervical Squamous Carcinomas

PubMed Central

Molinolo, Alfredo A.; Marsh, Christina; Dinali, Mohamed El; Gangane, Nitin; Jennison, Kaitlin; Hewitt, Stephen; Patel, Vyomesh; Seiwert, Tanguy Y.; Gutkind, J. Silvio

2012-01-01

Purpose The incidence of head and neck squamous cell carcinomas (HNSCC) associated with papillomavirus (HPV) infection has increased over the past decades in the US. We aimed at examining the global impact of HPV-associated HNSCC, and whether the established key role of mTOR activation in HNSCC is also observed in HPV+ HNSCC lesions, thereby providing novel treatment options for HPV-associated HNSCC patients. Experimental Design An international HNSCC tissue microarray (TMA) was used to analyze the expression of p16INK4A, a surrogate for HPV infection, and Akt-mTOR pathway activation. Results were confirmed in a large collection of HPV− and HPV+ HNSCC cases and in a cervical cancer (CCSCC) TMA. Observations were validated in HNSCC and CCSCC-derived cell lines, which were xenografted into immunodeficient mice for tumorigenesis assays. Results Approximately 20% of all HNSCC lesions could be classified as HPV+, irrespective of their country of origin. mTOR pathway activation was observed in most HPV+ HNSCC and CCSCC lesions and cell lines. The pre-clinical efficacy of mTOR inhibition by rapamycin and RAD001 was explored in HPV+ HNSCC and CCSCC tumor xenografts. Both mTOR inhibitors effectively decreased mTOR activity in vivo, and caused a remarkable decrease in tumor burden. These results emphasize the emerging global impact of HPV-related HNSCCs, and indicate that the activation of the mTOR pathway is a widespread event in both HPV− and HPV-associated HNSCC and CCSCC lesions. Conclusions The emerging results may provide a rationale for the clinical evaluation of mTOR inhibitors as a molecular targeted approach for the treatment of HPV-associated malignancies. PMID:22409888

Cytology and high risk HPV testing in cervical cancer screening program: Outcome of 3-year follow-up in an academic institute.

PubMed

Yang, Jack; Nolte, Fredrick S; Chajewski, Olga S; Lindsey, Kathryn G; Houser, Patricia M; Pellicier, Jalidsa; Wang, Qun; Ehsani, Laleh

2018-01-01

Combination of cervical cytology and high-risk human papillomavirus (HR-HPV) testing, co-testing, has been increasingly used in screening cervical cancers. The present study summarized the outcome of co-testing by reviewing 3-year clinical and pathological follow-up information. Patients were retrospectively identified via computerized search and were grouped based on the cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past medical history and follow-up information were analyzed. During 3-year follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%) patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC-US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of 159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%) with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US, respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up cervical biopsy. HR-HPV testing plays an important role in cervical cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co-testing is an optimal method to identifying the patients with higher risk for developing cervical abnormalities. © 2017 Wiley Periodicals, Inc.

Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-05-18

CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Squamous cell carcinoma of the anal sac in five dogs.

PubMed

Esplin, D G; Wilson, S R; Hullinger, G A

2003-05-01

Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.

[Factors associated with abnormal cervical cytology in pregnant women].

PubMed

Fan, Ling; Zou, Li-ying; Wu, Yu-mei; Zhang, Wei-yuan

2010-02-01

To investigate the risk factors associated with abnormal cervical cytology findings in pregnant women. From Sep. 2007 to Sep. 2008, 12,112 pregnant women who underwent their antenatal examinations at 12-36 gestational weeks in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. They were all excluded from the following pathologic obstetrics factors including threatened abortion, premature rupture of membranes or placental previa. Thinprep cytology test (TCT) were given at their first examination, meanwhile, a personal clinic file was established to record her occupation, education, address, family income, nationality, age of first intercourse, number of sex partners, contraception, marriage and pregnancy, current gynecologic diseases, family history of gynecologic tumors, history of gynecologic diseases and smoking and result of pelvic examination. Those risk factors leading to abnormal cervical cytology were analyzed. The complete clinical data were collected from 11 906 cases (98.30%, 11,906/12,112). It was found that 10,354 women were shown with normal TCT result, however, 1134 women (9.52%, 1134/11,906) with atypical squamous cells of undetermined significance (ASCUS), 112 women (0.94%, 112/11,906) with atypical glandular cells of undetermined significance (AGUS), 229 women (1.92%, 229/11,906) with low grade squamous intraepithelial (LSIL), 74 women (0.62%, 74/11,906) with high grade squamous intraepithelial (HSIL). Multiple factorial non-conditioned logistic regression analysis showed that age of first sexual intercourse (OR(ASCUS) = 2.90, OR(AGUS) = 7.32), number of sex partners (OR(ASCUS) = 1.49, OR(AGUS) = 2.02), number of abortion (OR(ASCUS) = 1.68, OR(AGUS) = 3.50) were correlated with ASCUS and AGUS. In LSIL group and HSIL group, age of first sexual intercourse (OR(LSIL) = 6.34, OR(HSIL) = 9.26), number of sex partners (OR(LSIL) = 1.69, OR(HSIL) = 1.65), number of abortion (OR(LSIL) = 1.53, OR(HSIL) = 5.33), smoking (OR(LSIL) = 1

VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-11

Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

PubMed

Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2018-01-01

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-07-01

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis

PubMed Central

Cui, Ning-hua; Zhang, Shuai; Wang, Chen; Zheng, Fang

2017-01-01

To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis. PMID:27669738

Human papillomavirus (HPV) and Oropharyngeal Squamous Cell Carcinoma (OP-SCC) of the Head and Neck: a Growing Epidemic

PubMed Central

Bauman, Jessica; Wirth, Lori

2015-01-01

Human papillomavirus (HPV) is now considered a major causative agent in oropharyngeal squamous cell carcinoma (OP-SCC). The incidence of HPV+ OP-SCC is increasing dramatically, is higher in men, and is now more common than cervical cancer in the United States. HPV+ OPSCCs usually present as locally advanced, stage IV cancers, requiring intensive treatment with surgery, chemotherapy, and/or radiation that can cause tremendous morbidity. HPV vaccination is predicted to prevent HPV+ OP-SCC because over 90% are caused by vaccine-type HPV. However, current vaccination rates are not yet high enough to be effective at preventing HPV-associated malignancies at a population level. PMID:27132327

Re-irradiation for head and neck squamous cell carcinoma.

PubMed

Benson, Rony; Giridhar, Prashant; Venkatesulu, Bhanu Prasad; Mallick, Supriya; Raza, Mohd Waseem; Rath, Goura Kishor

2017-03-01

Local recurrences after curative treatment have a potential for cure with salvage surgery or with re-irradiation. We reviewed the PubMed for articles published in English with key words squamous cell carcinoma, recurrent, re-irradiation, prognostic factors to find relevant articles describing prognostic factors, re-irradiation, and outcome for recurrent head and neck squamous cell carcinoma. Various factors including age, performance status, time for recurrence, previous radiation dose volume and site of recurrence, previous use of chemotherapy are all prognostic factors in recurrent head and neck squamous cell carcinoma. Surgery is feasible in very select subgroup of patients and must be done when feasible. Re-irradiation with the aid of modern sophisticated technology is safe and confers durable and clinically meaningful survival benefit. Re-irradiation in head and neck recurrent squamous cell carcinoma may provide an expected median survival of 10-12months. Chemotherapy may be added along with radiation in the recurrent setting. Treatment approaches may have to be personalized. Re surgery must be done in all patients in whom it is feasible. In patients in whom surgery is not feasible, re-irradiation must be evaluated as a therapeutic option especially in patients with limited volume recurrence. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

Squamous cell carcinoma in chronic wound: Marjolin ulcer.

PubMed

Cocchetto, Vanessa; Magrin, Paula; de Paula, Roberta Andrade; Aidé, Márcia; Monte Razo, Leonardo; Pantaleão, Luciana

2013-02-15

Cutaneous squamous cell carcinoma (SCC) is a malignant tumor that can occur in normal skin, but commonly evolves from precursor lesions. SCC arising in ulcers is a rare and often aggressive cutaneous malignancy that arises from chronic wounds or old scars and is the most common histological tumor type found in Marjolin ulcer. Most frequently occurs in patients of low socioeconomic status, with limited access to health services, as a result of burns and other neglected injuries. Herein, we report a case of squamous cell carcinoma originating from a longstanding decubitus ulcer in a 56-year-old paraplegic man.

Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

PubMed Central

Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

2014-01-01

Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma.

PubMed

Liu, Kang; Song, Guiqin; Zhang, Xuqian; Li, Qiujiang; Zhao, Yunxia; Zhou, Yuchuan; Xiong, Rong; Hu, Xin; Tang, Zhirong; Feng, Gang

2017-05-25

Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer. We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration. Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells. PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.

Squamous cell carcinoma of the anal and perianal area in a bull.

PubMed

Musser, J M; Russell, K E; Veatch, J K; St-Jean, G

1993-01-01

A squamous cell carcinoma located adjacent to the anus was diagnosed in a 15-year-old light colored Longhorn bull. The tumor restricted the anal orifice to a diameter of 3 cm. Upon histological evaluation, islands of squamous cells were present deep in the dermis and the submucosal connective tissue. It was not possible to determine whether the tumor originated from the perianal region or the anus. This is the first diagnosed and reported occurrence in North America of squamous cell carcinoma in the anal region of a bull.

Effect of Lower Anogenital Squamous Terminology Recommendations on the Use of p16 Immunohistochemistry and the Proportion of High-Grade Diagnoses in Cervical Biopsy Specimens.

PubMed

Thrall, Michael J

2016-04-01

The Lower Anogenital Squamous Terminology (LAST) group has recommended that cervical intraepithelial neoplasia (CIN) terminology be replaced by squamous intraepithelial lesion (SIL) terminology, with p16 immunohistochemistry used to separate lesions formerly diagnosed as CIN grade 2 into high-grade SILs (HSILs) and low-grade SILs. This study investigated the impact of these changes on the frequency of p16 testing and the diagnosis of high-grade lesions. Pathology reports for all cervical biopsy specimens in the 1 year before and after the introduction of LAST recommendations (July 2011 to June 2013) were examined. Before and after the implementation of LAST, 365 (15.4%) of 2,376 cases were diagnosed as high grade (CIN 2/3) vs 486 (17.6%) of 2,761 cases diagnosed as HSILs (P = .0343), and p16 was performed 79 (3.3%) times vs 383 (13.9%) times (P < .0001). Immunohistochemistry for p16 increased dramatically as a result of LAST recommendations, and high-grade diagnoses increased. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Solitary Splenic Metastasis After Surgically-treated Cervical Cancer - A Case Report and Literature Review.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Marcu, Madalina; Oprescu, Dana Nuti; Anca, Alexandru Florin

2017-05-01

Solitary metastases after surgically-treated cervical cancer are a rare entity, with only few cases described so far. We present the case of a 31-year-old patient diagnosed with a tumoral splenic lesion at 18 months after surgically-treated cervical cancer. The patient was submitted to surgery, with a splenectomy being performed. The histopathological studies confirmed the presence of a squamous cell cervical cancer splenic metastasis. At one year follow-up after splenectomy, the patient is free of any recurrent disease. Solitary splenic metastases after surgically-treated cervical cancer are rarely seen; however, this diagnostic should not be omitted whenever a medical history of cervical cancer is present. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Poorly Differentiated Squamous Cell Carcinoma Arising in Tattooed Skin

PubMed Central

Sarma, Deba P.; Dentlinger, Renee B.; Forystek, Amanda M.; Stevens, Todd; Huerter, Christopher

2010-01-01

Introduction. Tattoos have increasingly become accepted by mainstream Western society. As a result, the incidence of tattoo-associated dermatoses is on the rise. The presence of a poorly differentiated squamous cell carcinoma in an old tattooed skin is of interest as it has not been previously documented. Case Presentation. A 79-year-old white homeless man of European descent presented to the dermatology clinic with a painless raised nodule on his left forearm arising in a tattooed area. A biopsy of the lesion revealed a poorly differentiated squamous cell carcinoma infiltrating into a tattoo. The lesion was completely excised and the patient remains disease-free one year later. Conclusion. All previous reports of squamous cell carcinomas arising in tattoos have been well-differentiated low-grade type or keratoacanthoma-type and are considered to be coincidental rather than related to any carcinogenic effect of the tattoo pigments. Tattoo-associated poorly differentiated invasive carcinoma appears to be extremely rare. PMID:21274289

Association between concurrent genital bleeding and cervical cancer: a cross-sectional study.

PubMed

Xavier-Júnior, José C C; Vale, Diama B; Zeferino, Luiz C; Dufloth, Rozany M

2015-09-01

Genital bleeding may be a common symptom among women with cervical cancer. Cross-sectional study evaluating whether the prevalence of cervical smear results is different in women with and without clinical information about concurrent genital bleeding. The sample consisted of 2 324 836 smears; of these, 0.4% had clinical information on genital bleeding. When stratified by age group, women with genital bleeding had a higher chance of a cytological result of a high-grade squamous intraepithelial lesion [30-49 years odds ratio (OR) 2.38; 95% confidence interval (CI) 1.60-3.53 and ≥50 years OR 6.30; 95%CI 3.72-10.67), of squamous cell carcinoma (SCC) (30-49 years OR 24.70; 95%CI 11.96-51.03 and ≥50 years OR 48.91; 95%CI 31.28-76.47) and of atypical glandular cells (30-49 years OR 5.72; 95%CI 3.30-9.93 and ≥50 years OR 11.56; 95%CI 5.96-22.45); there was also a higher chance of adenocarcinoma for women ≥50 years (OR 53.13; 95%CI 28.08-100.51). The sensitivity of genital bleeding for women aged 18-29 years was 0.4% for high-grade squamous intraepithelial lesion (HSIL); for women 30-49 years old the rate was 0.9% for HSIL, 8.6% for SCC and 2.1% for atypical glandular cells of undetermined significance (AGUS), while for women aged from 50 years or more the rates were 2.0% for HSIL, 13.7% for SCC, 3.6% for AGUS and 14.7% for adenocarcinoma. Women ≥30 years old with genital bleeding should be referred for colposcopy to rule out the possibility of cervical cancer. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

PubMed

Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

2016-01-01

To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

PubMed

Couture, Émilie L; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

2015-12-01

A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors' knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species.

Identification of Significant Gene Signatures and Prognostic Biomarkers for Patients With Cervical Cancer by Integrated Bioinformatic Methods

PubMed Central

Li, Xiaofang; Tian, Run; Gao, Hugh; Yan, Feng; Ying, Le; Yang, Yongkang; Yang, Pei

2018-01-01

Cervical cancer is the leading cause of death with gynecological malignancies. We aimed to explore the molecular mechanism of carcinogenesis and biomarkers for cervical cancer by integrated bioinformatic analysis. We employed RNA-sequencing details of 254 cervical squamous cell carcinomas and 3 normal samples from The Cancer Genome Atlas. To explore the distinct pathways, messenger RNA expression was submitted to a Gene Set Enrichment Analysis. Kyoto Encyclopedia of Genes and Genomes and protein–protein interaction network analysis of differentially expressed genes were performed. Then, we conducted pathway enrichment analysis for modules acquired in protein–protein interaction analysis and obtained a list of pathways in every module. After intersecting the results from the 3 approaches, we evaluated the survival rates of both mutual pathways and genes in the pathway, and 5 survival-related genes were obtained. Finally, Cox hazards ratio analysis of these 5 genes was performed. DNA replication pathway (P < .001; 12 genes included) was suggested to have the strongest association with the prognosis of cervical squamous cancer. In total, 5 of the 12 genes, namely, minichromosome maintenance 2, minichromosome maintenance 4, minichromosome maintenance 5, proliferating cell nuclear antigen, and ribonuclease H2 subunit A were significantly correlated with survival. Minichromosome maintenance 5 was shown as an independent prognostic biomarker for patients with cervical cancer. This study identified a distinct pathway (DNA replication). Five genes which may be prognostic biomarkers and minichromosome maintenance 5 were identified as independent prognostic biomarkers for patients with cervical cancer. PMID:29642758

Cervical Cancer Incidence in Young U.S. Females After Human Papillomavirus Vaccine Introduction.

PubMed

Guo, Fangjian; Cofie, Leslie E; Berenson, Abbey B

2018-05-30

Since 2006, human papillomavirus vaccine has been recommended for young females in the U.S. This study aimed to compare cervical cancer incidence among young women before and after the human papillomavirus vaccine was introduced. This cross-sectional study used data from the National Program for Cancer Registries and Surveillance, Epidemiology, and End Results Incidence-U.S. Cancer Statistics 2001-2014 database for U.S. females aged 15-34 years. This study compared the 4-year average annual incidence of invasive cervical cancer in the 4 years before human papillomavirus vaccine was introduced (2003-2006) and the 4 most recent years in the vaccine era (2011-2014). Joinpoint regression models of cervical incidence from 2001 to 2014 were fitted to identify the discrete joints (year) that represent statistically significant changes in the direction of the trend after the introduction of human papillomavirus vaccination in 2006. Data were collected in 2001-2014, released, and analyzed in 2017. The 4-year average annual incidence rates for cervical cancer in 2011-2014 were 29% lower than that in 2003-2006 (6.0 vs 8.4 per 1,000,000 people, rate ratio=0.71, 95% CI=0.64, 0.80) among females aged 15-24 years, and 13.0% lower among females aged 25-34 years. Joinpoint analyses of cervical cancer incidence among females aged 15-24 years revealed a significant joint at 2009 for both squamous cell carcinoma and non-squamous cell carcinoma. Among females aged 25-34 years, there was no significant decrease in cervical cancer incidence after 2006. A significant decrease in the incidence of cervical cancer among young females after the introduction of human papillomavirus vaccine may indicate early effects of human papillomavirus vaccination. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Paracoccidioidomycosis: report of 2 cases mimicking squamous cell carcinoma.

PubMed

Meneses-García, Abelardo; Mosqueda-Taylor, Adalberto; Morales-de la Luz, Rosario; Rivera, Luz María Ruíz-Godoy

2002-11-01

Paracoccidioidomycosis is an endemic fungal infection in Latin America. This mucocutaneous disease often involves the oral mucosa and may clinically resemble other infectious and neoplastic processes. Paracoccidioidomycosis that clinically suggested squamous cell carcinoma was diagnosed in 2 patients with a history of heavy alcohol and tobacco use. Antifungal therapy with ketoconazole and itraconazole resulted in resolution of the oral lesions. Interestingly, 1 patient had a pulmonary lesion that persisted after antifungal therapy, and biopsy proved this to be a squamous cell carcinoma of the lung.

[Actinic keratosis, Bowen's disease, keratoacanthoma and squamous cell carcinoma of the skin].

PubMed

Majores, M; Bierhoff, E

2015-02-01

Actinic (solar) keratosis is an intraepidermal squamous neoplasm of sun-damaged skin and by far the most frequent neoplastic skin lesion. A subdivison into three grades has been proposed with increasing acceptance not least because of the therapeutic consequences. The transition to invasive squamous cell carcinoma is reported in 5-10 % and with immunosuppression in 30 % of patients.Bowen's disease is a variant of squamous cell carcinoma in situ of the skin and the mucocutaneous junction. The differentiation from bowenoid papulosis as a lesion associated with human papillomavirus (HPV), actinic (solar) keratosis grade III, intraepidermal poroid lesions and in cases of clonal type from clonal seborrhoic keratosis and Paget's disease is very important.Keratoacanthoma is currently uniformly interpreted as a variant of highly differentiated squamous cell carcinoma of the skin with clinical and histomorphological characteristics. Clinically keratoacanthoma erupts rapidly and is capable of resolving spontaneously. Histologically, there is a characteristic growth pattern and various stages of regression. The final histomorphological diagnosis needs the entire specimen.Squamous cell carcinoma of the skin is the second most common type of skin cancer following basal cell carcinoma. With respect to reccurrencies and risk of metastases the subtyping of cutaneous squamous cell carcinoma is very important. The classification system of the Union Internationale Contra le Cancer (UICC) is based solely on the anatomical spread and the classification system of the American Joint Committee on Cancer (AJCC) also considers so-called high-risk features in the staging between stages I and II.

Triage of women with atypical squamous cells of undetermined significance (ASC-US): results of an Italian multicentric study.

PubMed

Del Mistro, Annarosa; Frayle-Salamanca, Helena; Trevisan, Rossana; Matteucci, Mario; Pinarello, Antonella; Zambenedetti, Pamela; Buoso, Rita; Fantin, Gian Piero; Zorzi, Manuel; Minucci, Daria

2010-04-01

To compare the performance of immediate colposcopy, repeat Pap test and HPV test as triage options for women diagnosed as having atypical squamous cells of undetermined significance (ASC-US) while attending organised screening for cervical carcinoma in five centres of the Veneto region. Women consecutively diagnosed as having ASC-US were included in a prospective study, and underwent colposcopy and collection of cervico-vaginal cells for conventional Pap test and HPV test (Hybrid Capture 2, High-risk probe set, Digene). Repetition of all three tests was scheduled for 12 months later. DNA was subsequently extracted from residual cells of positive samples, and analysed by polymerase chain reaction with several primers for typing of HPV sequences. Sensitivity, specificity and positive predictive value (PPV) of the different triage options for histology-confirmed cervical intraepithelial neoplasia, grade 2 or worse (CIN2+) were calculated among all women and by age (under and above 35 years). Seven hundred forty-nine women 25-64 years old (median age 42 years) were enrolled in the study. Pap smears at enrolment were read as ASC-US or more severe in 211 (29.4%) cases, colposcopy disclosed an atypical transformation zone in 254 (34.2%) women, and HPV test was positive in 181 (24.2%). High-grade cervical lesions developed in 29/749 (3.9%) women. HPV typing was possible in 163 (90%) of the samples, and carcinogenic types were present in 123. HPV test showed the best performance; overall, it had the highest sensitivity (92.3%), specificity (78.6%) and PPV (14.9%). Copyright 2009 Elsevier Inc. All rights reserved.

Squamous cell carcinoma of the breast as a clinical diagnostic challenge

PubMed Central

Jakubowska, Katarzyna; Kańczuga-Koda, Luiza; Kisielewski, Wojciech; Koda, Mariusz; Famulski, Waldemar

2018-01-01

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice. PMID:29556390

Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris)

PubMed Central

Couture, Émilie L.; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

2015-01-01

A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors’ knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species. PMID:26663924

Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance.

PubMed

Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

2015-03-01

Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated. Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034). Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

Treatment of Squamous Cell Carcinoma of the Skin by Electrodesiccation and Curettage

PubMed Central

Williamson, George S.; Jackson, Robert

1964-01-01

Results of treatment of 108 squamous cell carcinomas of the skin are analyzed. Fiftyone were successfully treated by the technique of electrodesiccation and curettage. There were two treatment failures by this method. Large squamous cell cancers showing histologically a marked degree of anaplasia and/or invasion are not suitable for this technique. Small squamous cell carcinomas, well differentiated, with minimal invasion, occurring on the exposed areas, in elderly and infirm patients can be treated successfully by electrodesiccation and curettage. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8 PMID:14123665

Esophageal squamous cell carcinoma with dural and bone marrow metastases.

PubMed

Chen, Yen-Hao; Huang, Cheng-Hua

2014-09-21

Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

Squamous cell carcinoma in exstrophy of the bladder.

PubMed

Sharma, Pramod Kumar; Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

2013-08-01

Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature.

Squamous Cell Carcinoma in Exstrophy of the Bladder

PubMed Central

Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

2013-01-01

Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature. PMID:23956833

Computer-aided screening system for cervical precancerous cells based on field emission scanning electron microscopy and energy dispersive x-ray images and spectra

NASA Astrophysics Data System (ADS)

Jusman, Yessi; Ng, Siew-Cheok; Hasikin, Khairunnisa; Kurnia, Rahmadi; Osman, Noor Azuan Bin Abu; Teoh, Kean Hooi

2016-10-01

The capability of field emission scanning electron microscopy and energy dispersive x-ray spectroscopy (FE-SEM/EDX) to scan material structures at the microlevel and characterize the material with its elemental properties has inspired this research, which has developed an FE-SEM/EDX-based cervical cancer screening system. The developed computer-aided screening system consisted of two parts, which were the automatic features of extraction and classification. For the automatic features extraction algorithm, the image and spectra of cervical cells features extraction algorithm for extracting the discriminant features of FE-SEM/EDX data was introduced. The system automatically extracted two types of features based on FE-SEM/EDX images and FE-SEM/EDX spectra. Textural features were extracted from the FE-SEM/EDX image using a gray level co-occurrence matrix technique, while the FE-SEM/EDX spectra features were calculated based on peak heights and corrected area under the peaks using an algorithm. A discriminant analysis technique was employed to predict the cervical precancerous stage into three classes: normal, low-grade intraepithelial squamous lesion (LSIL), and high-grade intraepithelial squamous lesion (HSIL). The capability of the developed screening system was tested using 700 FE-SEM/EDX spectra (300 normal, 200 LSIL, and 200 HSIL cases). The accuracy, sensitivity, and specificity performances were 98.2%, 99.0%, and 98.0%, respectively.

Behavior of squamous cell carcinoma of the floor of the mouth. Is supraomohyoid neck dissection sufficiently safe to manage clinically N0 patients?

PubMed

Cariati, Paolo; Cabello Serrano, Almudena; Roman Ramos, Maria; Sanchez Lopez, Dario; Fernandez Solis, Jose; Martinez Lara, Ildefonso

2018-05-11

The main aim of the present report is to study the behavior of SCC of the floor of the mouth. A retrospective analysis was conducted using the records of patients diagnosed with squamous cell carcinoma of the floor of the mouth between 2000 and 2012 in the HUVN. Ninety-three patients with squamous cell carcinoma of the floor of the mouth treated with tumourectomy and selective neck dissection were included in the study. The pattern of distribution of cervical metastases and numerous histological features such as T-stage, N stage, surgical margins, tumor thickness, ECS (extracapsular spread) and vascular invasion were analyzed. Level I was the most affected level, followed by Level II. T stage, tumor thickness, and surgical margins showed a strong relationship with the risk of developing a local or cervical failure at follow-up. Overall survival was 52.7%. T stage, tumor thickness, N stage, recurrence, extracapsular spread, and vascular invasion were also associated with a poor prognosis. SCC of the floor of the mouth is an aggressive disease even at early stages. Due to the low rate of positive nodes observed at level IV and V in clinically N0 patients, supraomohyoid neck dissection might be considered sufficiently safe in this group. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

PubMed

Kashofer, Karl; Winter, Elke; Halbwedl, Iris; Thueringer, Andrea; Kreiner, Marisa; Sauer, Stefan; Regauer, Sigrid

2017-07-01

The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 ink4a overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained. Thirty of 76 squamous cell carcinomas (43%; average 63 years) were HPV-negative with 8/33 squamous cell carcinomas being TP53 wild-type (24%; average 63 years). Twenty-five of 33 squamous cell carcinomas (76%; average 65 years) showed 32 different somatic TP53 mutations (23 missense mutations in exons 5-8, 6 nonsense, 1 frameshift and 2 splice-site mutations). Several hotspot mutations were detected multiple times (R175H, R248, R282, and R273). Eighteen of 19 squamous cell carcinomas with TP53 expression in immunohistochemistry had TP53 mutations. Fifty percent of TP53-negative squamous cell carcinomas showed mostly truncating loss-of-function TP53 mutations. Patients without mutations had longer survival (5 years: 86% vs 61%; 10 years: 60% vs 22%), but valid clinically relevant conclusions cannot be drawn due to different tumor stages and heterogeneous treatment of the cases presented in this study. Somatic TP53 mutations are a common feature in HPV-negative penile squamous cell carcinomas and offer an explanation for HPV-independent penile carcinogenesis. About half of HPV-negative penile cancers are driven by oncogenic activation of TP53, while a quarter is induced by loss of TP53 tumor suppressor function. Detection of TP53 mutations should be carried out by sequencing, as immunohistochemical TP53 staining could not identify all squamous cell carcinomas with TP53 mutations.

Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

PubMed Central

Ali, Liaquat; Hassan, Zahid; Khan, Imran

2013-01-01

Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18. PMID:23617206

Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.

PubMed

Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

2013-03-01

Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.

Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ

PubMed Central

ANDERSSON, SONIA; MINTS, MIRIAM; WILANDER, ERIK

2013-01-01

The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged ≤32 years, while patients aged ≥38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing cofactor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination. PMID:23946807

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

PubMed

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

PubMed Central