Cervical cancer is a common type of malignancy accounting for about 6% of all cancers found in women. It is a disease in which cancerous cells develop in the uterine cervix (this is the connecting passage between the uterus and vagina). The human papillomaviruses (HPV) are the principal cause of most cervical cancers. The peak incidence of cervical cancer occurs between the ages of 40 to 55. It is rare before the age of 35, however the incidence of cervical cancer in younger women rose dramatically during the two decades after 1960. Regular Pap smear tests may detect abnormal changes in the cervical tissues, before cancer develops. Symptoms of cervical cancer may include vaginal bleeding after intercourse or bleeding between periods. However, in the early stages of the disease there are often no obvious signs or symptoms, so regular smear tests are important.
healthtalkonline.org Detailed information, including snippets from interviews with 25 women, who share their experiences on a broad range of topics related to cervical cancer and treatment and side effects.
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PubMed Central search for free-access publications about Cervical Cancer MeSH term: Uterine Cervical Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
A non-profit organisation founded in 1991 to increase awareness and education, support expanded research and training, and provide knowledge and hope for women
diagnosed with cancers specific to them. Gynacological Cancers
SGO A professional membership organisation encouraging research, providing education, raising standards of practice, advocating for patients and members and collaborating with other domestic and international organizations. US + international members. Gynacological CancersGynecologic Oncology
This list of publications is regularly updated (Source: PubMed).
Shen S, Zhang Y, Zhang R, Gong X Sarsasapogenin induces apoptosis via the reactive oxygen species-mediated mitochondrial pathway and ER stress pathway in HeLa cells. Biochem Biophys Res Commun. 2013; 441(2):519-24 [PubMed] Related Publications
Sarsasapogenin is a sapogenin from the Chinese medical herb Anemarrhena asphodeloides Bunge. In the present study, we revealed that sarsasapogenin exhibited antitumor activity by inducing apoptosis in vitro as determined by Hoechst staining analysis and double staining of Annexin V-FITC/PI. In addition, cell cycle arrest in G2/M phase was observed in sarsasapogenin-treated HeLa cells. Moreover, the results revealed that perturbations in the mitochondrial membrane were associated with the deregulation of the Bax/Bcl-2 ratio which led to the upregulation of cytochrome c, followed by activation of caspases. Meanwhile, treatment of sarsasapogenin also activated Unfolded Protein Response (UPR) signaling pathways and these changes were accompanied by increased expression of CHOP. Salubrinal (Sal), a selective inhibitor of endoplasmic reticulum (ER) stress, partially abrogated the sarsasapogenin-related cell death. Furthermore, sarsasapogenin provoked the generation of reactive oxygen species, while the antioxidant N-acetyl cysteine (NAC) effectively blocked the activation of ER stress and apoptosis, suggesting that sarsasapogenin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways. Taken together, the results demonstrate that sarsasapogenin exerts its antitumor activity through both reactive oxygen species (ROS)-mediate mitochondrial dysfunction and ER stress cell death.
Ohayi SA, Ezugwu EC, Aderibigbe AS, Udeh EI Angiosarcoma of the cervix: a case and literature review. Niger J Med. 2013 Oct-Dec; 22(4):362-4 [PubMed] Related Publications
BACKGROUND: Generally, sarcomas of the female genital tract are rare and angiosarcomas are extremely rare. They usually have poor prognosis and pose serious diagnostic challenges requiring special techniques namely special stains and immunohistochemistry for proper elucidation. METHOD: A case report of a 65 old para 8 (4 alive) widow, 17 years postmenopusal, who presented with history of foul smelling brownish vaginal discharge, progressive weight loss and cervical lesion. She had examination under anaesthesia and biopsy. RESULT: Histopathological result showed features in keeping with angiosarcoma of the uterine cervix. CONCLUSION: Although angiosarcoma of the cervix is very rare, it is occasionally seen in black women in Nigeria.
Shuaibu SI, Gidado S, Oseni-Momodu E Endoscopic retrograde JJ-stenting of the ureter without fluoroscopy guidance--an appraisal of outcome. Niger J Med. 2013 Oct-Dec; 22(4):348-50 [PubMed] Related Publications
BACKGROUND: JJ- ureteral stenting is a means of relieving ureteric obstruction. It is done as a retrograde or antegrade procedure, usually under fluoroscopy guidance. We reviewed our results in 2 independent tertiary health centers in Nigeria which lack fluoroscopy units. METHODS: A 2 year retrospective review of data of patients who had retrograde JJ- ureteric stenting was done. Data relating to age, indication and outcome of procedure were retrieved and analysed. RESULTS: 22 (71%) patients had successful retrograde JJ- ureteric stenting out of 31 patients who were taken for the procedure. These 22 patients had stenting of 27 ureteric units. Mean age was 48.5 years. Commonest indication was carcinoma of the cervix (31.8%). Commonest complication was irritative lower urinary tract symptoms (43.5%). CONCLUSION: In spite of inherent complications, JJ-stenting is a simple and safe technique. Therefore, the decision to attempt JJ -stenting in carefully selected patients in the absence of fluoroscopy is acceptable.
Serdarevic N, Stanciu AE Comparison of Architect i2000 for determination of Scc with IMX determination of SCC with different methods. Clin Lab. 2013; 59(9-10):1129-33 [PubMed] Related Publications
BACKGROUND: SCC (squamous cell carcinoma) antigen (SSCA), a tumor marker, is already used for the diagnosis and follow-up of carcinoma of the cervix and lungs. The aim of our study was the determination of SCCA concentration in 96 serum samples using CMIA (chemiluminesecent microparticle immnoassay) on an Architect i2000 (Abbott Diagnostics) and MEIA (microparticle enzyme immnoassay) on an IMx Chemistry Analyzer (Abbott Diagnostics). METHODS: In our investigation we used a CMIA (chemiluminesecent microparticle immnoassay) Architect i2000 and MEIA (microparticle enzyme immnoassay) Imx Chemistry Analyzer for SCCA determination. RESULTS: All patients were hospitalized at the Department of Gynecologic Oncology and Department for Oncology at the University Clinics Center of Sarajevo. The normal serum range of SCCA should be < 0.1 microg/L. The quality control, precision and accuracy of the Architect i2000 were assessed. The quality control was done using quality control serums for low (X = 2.17 microg/L), medium (X = 10.23 microg/L), and high (X = 48.99 microg/L) range. The precision for the Architect i2000 has a CV of 3.44% to 4.44%. We established that the main difference between Architect i2000 and IMx was statistically significant at p < 0.05 according to Student's t-test. The correlation coefficient was r = 0.990. The some samples have higher concentrations on the Architect than on the IMx because the sensitivity of the Architect assay is high (< 0.1 microg/L). CONCLUSIONS: The CMIA Architect technology is an applicable method significant in diagnostic of SCCA.
Lin Y, Chen Z, Kuang F, et al. Evaluation of international federation of gynecology and obstetrics stage IB cervical cancer: comparison of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging at 3.0 T. J Comput Assist Tomogr. 2013 Nov-Dec; 37(6):989-94 [PubMed] Related Publications
OBJECTIVE: The objective of this study was to compare the diagnostic performance of diffusion-weighted (DW) imaging with that of dynamic contrast-enhanced (DCE) imaging in the evaluation of tumor extent in patients with stage IB cervical cancer. METHODS: This retrospective study was approved by the institutional review board. Between June 2010 and March 2012, 46 consecutive patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB who underwent preoperative DCE, DW (b = 0 and 800 s/mm), and T1- and T2-weighted imaging were included in this study. Two radiologists independently evaluated the extent of cervical cancer and made a diagnosis of tumor stage according to the revised FIGO staging system. The staging accuracy by DCE and DW for readers 1 and 2 was compared with the McNemar test, and κ statistics were used for reader agreement. RESULTS: No statistical difference between the diagnostic performance of staging with DCE and with DW was observed in reader 1 (P = 1.000) or in reader 2 (P = 0.109). Interobserver agreement between the 2 readers for staging was both substantial with DCE (κ = 0.750, P < 0.001) and with DW (κ = 0.683, P < 0.001). CONCLUSIONS: The diagnostic performance of DW in distinguishing the subdivision of stage IB cervical cancer was not statistically different from that of DCE. Diffusion-weighted imaging may be preferable to DCE for the preoperative evaluation of stage IB cervical cancer.
Lertworapreecha M, Patumraj S, Niruthisard S, et al. Cytotoxic function of gamma delta (gamma/delta) T cells against pamidronate-treated cervical cancer cells. Indian J Exp Biol. 2013; 51(8):597-605 [PubMed] Related Publications
The cytotoxic function of polyclonal expanded gamma/delta T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The gamma/delta T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 microM pamidronate. The expansion of gamma/delta T cells was 15 times more than the non-stimulated cells. Among the expanded gamma/delta T cells, 47% were Vgamma9/Vdelta2 T cells with a purity of 87%. Analyzing the cytotoxic function of gamma/delta T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on gamma/delta T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the gamma/delta T cells to kill cancer cells. The killing ability of gamma/delta T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that gamma/delta T cells induce apoptosis in tumor cells. Our study supports the usefulness of gamma/delta T cells in future development of immunotherapy for cervical cancer.
Godfrey CC, Michelow PM, Godard M, et al. Improving diagnostic capability for HPV disease internationally within the NIH-NIAID Division of AIDS Clinical Trial Networks. Am J Clin Pathol. 2013; 140(6):881-9 [PubMed] Related Publications
OBJECTIVES: To evaluate an external quality assurance (EQA) program for the laboratory diagnosis of human papillomavirus (HPV) disease that was established to improve international research capability within the Division of AIDS at the National Institute of Allergy and Infectious Disease-supported Adult AIDS Clinical Trials Group network. METHODS: A three-component EQA scheme was devised comprising assessments of diagnostic accuracy of cytotechnologists and pathologists using available EQA panels, review of quality and accuracy of clinical slides from local sites by an outside expert, and HPV DNA detection using a commercially available HPV test kit. RESULTS: Seven laboratories and 17 pathologists in Africa, India, and South America participated. EQA scores were suboptimal for EQA proficiency testing panels in three of seven laboratories. There was good agreement between the local laboratory and the central reader 70% of the time (90% confidence interval, 42%-98%). Performance on the College of American Pathologists' HPV DNA testing panel was successful in all laboratories tested. CONCLUSIONS: The prequalifying EQA round identified correctable issues that will improve the laboratory diagnosis of HPV-related cervical disease at the participating international study sites and will provide a mechanism for ongoing education and continuous quality improvement.
Jeon HW, Suh DH, Kim K, et al. Lymphadenectomy alone is a feasible option in managing incidentally-detected early-stage cervical cancer after simple hysterectomy without intermediate-risk factors: An application of the concept of less radical surgery. Anticancer Res. 2013; 33(11):5135-41 [PubMed] Related Publications
AIM: To assess the feasibility of less radical surgery in patients with incidentally-detected cervical cancer at simple hysterectomy. PATIENTS AND METHODS: High-risk factors (HFs) were evaluated in 104 patients who underwent radical hysterectomy and lymphadenectomy for the treatment of stage IA1-IB1 cervical cancer according to intermediate-risk factors (IFs). RESULTS: Thirty-three patients without IFs had no HFs. As the number of IFs increased, the number of HFs increased (p=0.009). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for parametrial involvement (hazard ratio, 31.3; 95% confidence interval, 1.6-599.4; p=0.022). An absence of IFs was associated with a longer progression-free survival than the presence of IFs in the subgroup analysis of favorable histologies (p=0.044). CONCLUSION: HFs could be excluded in stage IA1-IB1 cervical cancer without IFs. Omitting parametrectomy seems a feasible option for selected patients with incidentally-detected early-stage cervical cancer at simple hysterectomy, without IFs.
Wakayama A, Inamine M, Kudaka W, et al. Concurrent chemoradiotherapy for non-bulky stage IB/II cervical cancer without pelvic node enlargement. Anticancer Res. 2013; 33(11):5123-6 [PubMed] Related Publications
BACKGROUND: Concurrent chemoradiotherapy (CCRT) has not been extensively studied in patients with small cervical cancer tumors with no pelvic node enlargement. PATIENTS AND METHODS: We retrospectively analyzed 55 patients with stage IB1-IIB cervical cancer and tumors of ≤40 mm with no pelvic node enlargement treated with radiotherapy (RT)-alone. RESULTS: Cancer recurred in seven patients. Patient age (≤63 years) was identified as an independent factor for better disease-free survival (DFS) (p=0.027), and tumor size (≥25 mm) had a tendency to correlate with reduced locoregional DFS (p=0.089) by the Cox hazard model. Among patients aged 63 years or less, cancer recurred in five out of 18 patients with tumors of ≥25 mm, but in only one of 10 patients with tumors of ≤24 mm. CONCLUSION: In patients with stage IB1-IIB cervical cancer and small tumors with no node enlargement, CCRT may provide a better disease control for the group aged 63 years or less and with tumor size of 25 mm or more.
Murakami N, Kasamatsu T, Morota M, et al. Radiation therapy for stage IVA cervical cancer. Anticancer Res. 2013; 33(11):4989-94 [PubMed] Related Publications
BACKGROUND: To evaluate the outcome and discover predictive factors for patients with stage IVA cervical cancer treated with definitive radiation therapy. PATIENTS AND METHODS: We retrospectively reviewed 34 patients with stage IVA cervical cancer who received definitive radiation therapy between 1992 and 2009. RESULTS: On univariate analysis, statistically significant prognostic factors for improved local control rate (LCR) were absence of pyometra (p=0.037) and equivalent dose in 2 Gy fractions (EQD2) at point A greater than 60 Gy (p=0.023). Prognostic factors for improved progression-free survival (PFS) were absence of pelvic lymph node metastasis at initial presentation (p=0.014), and EQD2 at point A greater than 60 Gy (p=0.023). CONCLUSION: Patients with stage IVA disease had poor median survival. However adequate radiation dose to point A produced favorable LCR and PFS, therefore efforts should be made to increase the point A dose.
Pieters HC, Wiley DJ Decision-making about cervical cancer screening methods by homeless women. J Natl Black Nurses Assoc. 2013; 24(1):9-15 [PubMed] Related Publications
To evaluate the perspectives and preferences of homeless women for traditional provider- and a novel low cost self-collected cytology screening technique, 17 interviews were conducted with women who participated in both phases of a comparative trial. Subjects were recruited from a comprehensive homeless service center and a residential program serving homeless women. Constructivist grounded theory guided data collection and analysis. Results showed self-collection was favored over provider-collected cytology, but that the women perceived that test accuracy trumped comfort. Although many women expressed inaccurate perceptions and beliefs about cervical cancer and screening, the women participated in and valued screening. Misconceptions about cervical malignancy and prevention strategies contributed to their complex appraisal of the two screening methods. Homeless women may partner with providers to develop and test effective interventions with high promise for improving their health and these insights may aid in developing effective interventions for diverse underserved communities.
Tirumani SH, Shanbhogue AK, Prasad SR Current concepts in the diagnosis and management of endometrial and cervical carcinomas. Radiol Clin North Am. 2013; 51(6):1087-110 [PubMed] Related Publications
Cross-sectional imaging modalities play a pivotal role in the diagnosis and multidisciplinary management of patients with endometrial and cervical carcinomas. Ultrasonography, including sonohysterography, permits evaluation of endometrial abnormalities and characterization of adnexal masses. Computed tomography, particularly in conjunction with (18)(F)-fluorodeoxyglucose positron emission tomography, is increasingly used to stage the cancers and to detect disease recurrence. Magnetic resonance imaging plays a major role in accurate locoregional staging of these cancers, and significantly influences treatment decisions and outcomes. This article discusses the role of imaging modalities in the diagnosis, management, and surveillance of these cancers.
Zeligs KP, Byrd K, Tarney CM, et al. A clinicopathologic study of vaginal intraepithelial neoplasia. Obstet Gynecol. 2013; 122(6):1223-30 [PubMed] Related Publications
OBJECTIVE: To evaluate the natural history of vaginal intraepithelial neoplasia (VAIN) and to identify risk factors for invasive vaginal carcinoma. METHODS: The records of all women with VAIN diagnosed at military treatment facilities over a 10-year period with minimum follow-up of 12 months were reviewed. Patient demographics and clinical information related to the diagnosis and treatment of VAIN were recorded. RESULTS: One hundred twenty-seven women with VAIN met inclusion criteria. The mean age was 47.4 years, and median surveillance was 34 months (range 12-169 months). Seventy-five patients had low-grade vaginal dysplasia as their initial diagnosis, and 15 (20%) of these patients underwent treatment. Fifty-two patients had high-grade vaginal dysplasia, of which 38 (73%) underwent treatment. Overall, 113 patients (89%) demonstrated normalization of disease, 11 patients (9%) demonstrated persistence of disease, and three patients (2%) experienced recurrence of disease. No patients experienced development of invasive vaginal carcinoma. However, median time to normalization was 6 months longer in patients with low-grade dysplasia compared with those with high-grade dysplasia (15.9 months compared with 10.0 months; hazard ratio 1.5; 95% confidence interval 1.004-2.1; P=.045). Patients with high-grade dysplasia had more biopsies performed during their surveillance than patients with low-grade dysplasia (3.3 compared with 2.5; P=.045). CONCLUSION: Overall, 89% of patients demonstrated normalization of VAIN, and none had progression to invasive cancer. Normalization, persistence, and recurrence rates did not significantly differ by grade of dysplasia or treatment status. Based on our findings regarding the time to normalization, annual surveillance with combined cytology and colposcopy is likely adequate. Because 11% of patients with VAIN either will experience recurrence or will have persistent disease, lifetime surveillance is recommended. LEVEL OF EVIDENCE: : III.
Hequet D, Marchand E, Place V, et al. Evaluation and impact of residual disease in locally advanced cervical cancer after concurrent chemoradiation therapy: results of a multicenter study. Eur J Surg Oncol. 2013; 39(12):1428-34 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the diagnosis and impact of residual disease (RD) after concurrent chemoradiation therapy (CRT) in locally advanced cervical cancer (FIGO IB2-IVA). METHODS: This retrospective multicenter study included 159 patients who were treated with completion surgery after CRT between 2006 and 2012. Magnetic resonance imaging (MRI) was performed 4-6 weeks after CRT and compared to pathological evidence of residual disease. Kaplan-Meier survival curves were plotted and univariate/multivariate analyses were performed to assess the association between RD and the outcome. RESULTS: Residual disease was present in 45.3% of the patients and detected by MRI in 57.1%. The MRI had a 29.2% false positive rate and an 11.1% false negative rate. The overall survival (OS) rates at 3 and 5 years were 78.6% (CI 95% [71%-86.9%]) and 76.5% (CI 95% [68.2%-85.7%]), respectively. The disease free survival (DFS) rates at 3 and 5 years were 73.4% (CI 95% [65.6%-82%]) and 71.1% (CI 95% [62.7%-80.1%]), respectively. RD greater than 10 mm decreased DFS (HR = 4.84, p = 0.03), whereas RD between 1 and 10 mm (HR = 0.31, p = 0.58) and less than 1 mm (HR = 0.37, p = 0.54) had no impact on DFS. The OS was not changed by RD. DISCUSSION: The MRI accuracy value is not sufficient to select patients who might benefit from completion surgery. Residual disease over 10 mm decreased DFS but did not impact OS.
Parish SL, Swaine JG, Son E, Luken K Determinants of cervical cancer screening among women with intellectual disabilities: evidence from medical records. Public Health Rep. 2013 Nov-Dec; 128(6):519-26 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
OBJECTIVE: We examined receipt of cervical cancer screening and determinants of screening for women with intellectual disabilities in one Southeastern state. METHODS: Using medical records data from 2006 through 2010 for community-dwelling women with intellectual disabilities who were 18-65 years of age (n=163), we employed descriptive and bivariate statistics and a multivariate regression model to examine receipt of cervical cancer screening and the determinants of cervical cancer screening across women's sociodemographic and health-care provider characteristics. RESULTS: Of women 18-65 years of age with intellectual disabilities, 55% received a Papanicolaou (Pap) test during 2008-2010, markedly below the Healthy People 2020 targets or rates of Pap test receipt of women without intellectual disabilities. Women with intellectual disabilities who lived in residential facilities, those who lived in rural communities, and those who had an obstetrician/gynecologist had higher rates of receipt of care than other women with intellectual disabilities. CONCLUSIONS: Assertive measures are required to improve the receipt of cervical cancer screening among women with intellectual disabilities. Such measures could include education of women with intellectual disabilities, as well as their paid and family caregivers, and incentives for health-care providers who achieve screening targets.
Hoogendam JP, Zaal A, Rutten EG, et al. Detection of cervical cancer recurrence during follow-up: a multivariable comparison of 9 frequently investigated serum biomarkers. Gynecol Oncol. 2013; 131(3):655-60 [PubMed] Related Publications
OBJECTIVE: To assess the diagnostic accuracy and model the optimal combination of commonly studied serum biomarkers aimed at identifying recurrence in cervical cancer patients. METHODS: From a systematic literature search, nine biomarkers (CA-15.3, CA-125, CEA, CYFRA 21-1, hsCRP, IL-6, SCC-Ag, TNF-α and VEGF) were selected for a serum analysis. Samples were derived from a historical cervical cancer cohort. Subjects with serum samples stored in a biobank were included when quality criteria were met, and one sample preceding and at least one following primary treatment were available. In case of recurrence, two additional post-recurrence samples were analyzed. Biomarker serum levels were quantified by enzyme linked or chemiluminescence microparticle immunoassays. Logistic regression and receiver operating curve analysis were employed for selection, modeling and comparison on the diagnostic accuracy of the tested biomarkers. RESULTS: 205 samples were analyzed from 75 subjects, of whom 19 (25.3%) had a recurrence. The area under the curve (AUC) of CA-15.3, CA-125, CEA, CYFRA 21-1, IL-6, TNF-α and VEGF were all <0.750. Only SCC-Ag and hsCRP were included in the final model with an AUC of 0.822 (95% CI: 0.744-0.900) and 0.831 (95% CI: 0.758-0.905) respectively. Combined AUC was 0.870 (95% CI: 0.805-0.935). Rises in SCC-Ag and hsCRP significantly increased the odds for recurrence. Each ng/ml of SCC-Ag increase, related to an odds ratio (OR) of 1.117 (95% CI: 1.039-1.200). Comparably, the OR for hsCRP (in mg/ml) was 1.025 (95% CI: 1.012-1.038). CONCLUSION: Combined testing of SCC-Ag and hsCRP yields the highest detection rate of disease recurrence during cervical cancer follow-up.
Chen YJ, Cheng YJ, Hung AC, et al. The synthetic flavonoid WYC02-9 inhibits cervical cancer cell migration/invasion and angiogenesis via MAPK14 signaling. Gynecol Oncol. 2013; 131(3):734-43 [PubMed] Related Publications
OBJECTIVE: Development of flavonoids as potential chemotherapeutic agents for cervical cancer may open new avenues in anticancer drug design. In this study, the cytotoxic activity and anti-migration/invasion/angiogenesis efficiency of the synthetic flavonoid WYC02-9 on cervical cancer and the underlying mechanisms are explored. METHODS: XTT cell viability assay, apoptosis assays, cell cycle analysis, and immunoblotting analysis were applied to study the biologic activity of WYC02-9. Anchorage independent soft agar assay and xenograft nude mouse model were applied to study the anti-tumor effect of WYC02-9 in vivo. Wound healing assay, transwell invasion assay, and gelatin zymography analysis were applied to study the effect of WYC02-9 on cancer cell migration and invasion. Tube formation analysis, zebrafish angiogenesis model, and nude mice Matrigel plug angiogenesis assay were applied to study the effect of WYC02-9 on angiogenesis. RESULTS: WYC02-9 induced cytotoxicity on cervical cancer cells by promoting apoptosis and G2/M cell cycle arrest. WYC02-9 inhibited cervical cancer cell migration/invasion and angiogenesis in vitro and in vivo via MAPK14 pathway. CONCLUSION: WYC02-9 significantly inhibited cervical cancer cell proliferation/migration/invasion and angiogenesis in vitro and in vivo. WYC02-9 may be a promising drug candidate for cervical cancer chemotherapy.
Lee YY, Kim TJ, Kim JY, et al. Genetic profiling to predict recurrence of early cervical cancer. Gynecol Oncol. 2013; 131(3):650-4 [PubMed] Related Publications
OBJECTIVE: Recurrence is the major cause of death in early cervical cancer. We compared the prediction powers for disease recurrence between the gene set prognostic model and the clinical prognostic model. MATERIALS AND METHODS: A gene set model to predict disease free survival was developed using the cDNA-mediated annealing, selection, extension, and ligation (DASL) assay data set from a cohort of early cervical cancer patients who had been treated with radical surgery with or without adjuvant therapy. A clinical prediction model was also developed using the same cohort, and the ability of predicting recurrence from each model was compared. RESULTS: Adequate DASL assay profiles were obtained from 300 patients, and we selected 12 genes for the gene set model. When patients were categorized as having a low or high risk by the prognostic score, the Kaplan-Meier curve showed significantly different recurrence rates between the two groups. The clinical model was developed using FIGO stage and post-surgical pathological findings. In multivariate Cox regression analysis of prognostic models, the gene set prognostic model showed a higher hazard ratio than that of the clinical prognostic model. CONCLUSIONS: The genetic quantitative approach may be better in predicting recurrence in early cervical cancer patients.
Yamanoi K, Matsumura N, Kido A, et al. A novel diagnostic criterion for lymph node metastasis in cervical cancer using multi-detector computed tomography. Gynecol Oncol. 2013; 131(3):701-7 [PubMed] Related Publications
OBJECTIVES: The sensitivity of the current 10mm cut-off diameter that is used to diagnose lymph node (LN) metastasis is too low. This is the first study to develop a new criterion to diagnose LN metastasis in a region-by-region manner using multi-detector computed tomography (MDCT). METHODS: 1) The short-axis diameter of the LNs in MDCT images from 1-mm slices obtained immediately prior to surgery was compared with the pathological diagnosis in 78 uterine cervical cancer patients undergoing primary surgery. For the region-by-region analysis, we divided para-aortic and pelvic spaces into 13 regions. 2) In 28 cases in which patients received neoadjuvant chemotherapy (NAC) followed by surgery, we compared MDCT images before and after NAC. RESULTS: 1) The optimal cut-off in the region-by-region analysis was 5mm, yielding 71% sensitivity and 79% specificity. 2) NAC significantly decreased LN size (p<0.0001). NAC decreased the number of swollen LN regions (>5mm) from 51% (81/158) to 26% (41/158). CONCLUSIONS: The new criterion developed using MDCT could be effective for accurately assessing LN status. It also facilitates the assessment of NAC efficacy regarding the eradication of LN metastases.
Huang EY, Chanchien CC, Lin H, et al. Galectin-1 is an independent prognostic factor for local recurrence and survival after definitive radiation therapy for patients with squamous cell carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys. 2013; 87(5):975-82 [PubMed] Related Publications
PURPOSE: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. METHODS AND MATERIALS: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. RESULTS: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. CONCLUSION: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.
Okonogi N, Saitoh J, Suzuki Y, et al. Changes in bone mineral density in uterine cervical cancer patients after radiation therapy. Int J Radiat Oncol Biol Phys. 2013; 87(5):968-74 [PubMed] Related Publications
PURPOSE: To prospectively investigate the changes in bone mineral density (BMD) after pelvic radiation therapy in patients with uterine cervical cancer. METHODS AND MATERIALS: Of 52 cervical cancer patients who received pelvic RT in our university hospital between 2009 and 2011, 46 patients without recurrence and who were followed up for more than 12 months were included in the study. The BMD of the irradiated region and nonirradiated regions, serum estradiol, tartrate-resistant acid phosphatase-5b, and N-terminal cross-linking telopeptide of collagen 1 were measured before, at 3 months after, and at 12 months after RT. The patient cohort was divided into 2 groups according to estradiol level before RT, and the groups were defined as postmenopausal (<40 pg/mL) and premenopausal (≥40 pg/mL). RESULTS: The mean BMDs within the irradiation field (lumbar vertebra 5) in the postmenopausal and the premenopausal groups were 0.825 and 0.910 g/cm(2) before RT and 0.746 and 0.841 g/cm(2) 12 months after RT, respectively. Significant decreases were observed in both groups (P<.05 and P<.01, respectively). In addition, in the premenopausal group the mean BMDs of the nonirradiated regions at thoracic vertebrae 9-12 and lumbar vertebrae 2-4 were 0.753 and 0.958 g/cm(2) before RT and were significantly decreased to 0.706 and 0.921 g/cm(2) 12 months after RT (P<.01 and P<.05, respectively). Estradiol significantly decreased 3 months after RT, whereas tartrate-resistant acid phosphatase-5b and N-terminal cross-linking telopeptide of collagen 1 continued to increase over time in the premenopausal group. CONCLUSIONS: A decrease in BMD in the irradiated region after RT was observed within 1 year, regardless of menopausal status. Furthermore, in premenopausal patients, pelvic RT caused a decrease in systemic BMD.
Lee HJ, Han S, Kim YS, et al. Individualized prediction of overall survival after postoperative radiation therapy in patients with early-stage cervical cancer: a Korean Radiation Oncology Group study (KROG 13-03). Int J Radiat Oncol Biol Phys. 2013; 87(4):659-64 [PubMed] Related Publications
PURPOSE: A nomogram is a predictive statistical model that generates the continuous probability of a clinical event such as death or recurrence. The aim of the study was to construct a nomogram to predict 5-year overall survival after postoperative radiation therapy for stage IB to IIA cervical cancer. METHODS AND MATERIALS: The clinical data from 1702 patients with early-stage cervical cancer, treated at 10 participating hospitals from 1990 to 2011, were reviewed to develop a prediction nomogram based on the Cox proportional hazards model. Demographic, clinical, and pathologic variables were included and analyzed to formulate the nomogram. The discrimination and calibration power of the model was measured using a concordance index (c-index) and calibration curve. RESULTS: The median follow-up period for surviving patients was 75.6 months, and the 5-year overall survival probability was 87.1%. The final model was constructed using the following variables: age, number of positive pelvic lymph nodes, parametrial invasion, lymphovascular invasion, and the use of concurrent chemotherapy. The nomogram predicted the 5-year overall survival with a c-index of 0.69, which was superior to the predictive power of the International Federation of Gynecology and Obstetrics (FIGO) staging system (c-index of 0.54). CONCLUSIONS: A survival-predicting nomogram that offers an accurate level of prediction and discrimination was developed based on a large multi-center study. The model may be more useful than the FIGO staging system for counseling individual patients regarding prognosis.
Schmidt MA, Gold R, Kurosky SK, et al. Uptake, coverage, and completion of quadrivalent human papillomavirus vaccine in the vaccine safety Datalink, July 2006-June 2011. J Adolesc Health. 2013; 53(5):637-41 [PubMed] Related Publications
PURPOSE: The Advisory Committee on Immunization Practices recommended quadrivalent human papillomavirus vaccine (HPV4) for use in females in June 2006 and in males in October 2009. The objective of our study was to describe HPV4 uptake, single-dose coverage, and completion of the three-dose series among those 9-26 years of age, after the respective female and male vaccine licensures through June 2011. METHODS: The study population included members of eight managed care organizations participating in the Vaccine Safety Datalink; we abstracted demographic and comprehensive vaccine information from electronic health records. RESULTS: We found one-dose coverage increasing throughout the study period, to a high of 37.7% among females and 1.3% among males in June 2011. Among those receiving at least one HPV4 dose, three-dose series completion was 42% for females and 30.2% for males. CONCLUSIONS: Our results demonstrate low initiation and completion of the HPV4 series among those recommended to receive the vaccine. Although consistent with previous studies, these results highlight the continued need to develop, implement, and monitor strategies to increase HPV4 vaccine initiation and completion in younger adolescents to achieve maximum impact in reducing the burden of cervical cancer and other HPV-related diseases.
Buchholtz ML, Jückstock J, Weber E, et al. Loss of LDOC1 expression by promoter methylation in cervical cancer cells. Cancer Invest. 2013; 31(9):571-7 [PubMed] Related Publications
Cervical cancer lacks reliable prognostic factors for both progression and chemotherapeutic responsiveness. The expression of the LDOC1 tumor suppressor candidate was therefore investigated. In four of six cervical cancer cell lines tested, expression of LDOC1 was silenced. Downregulation of LDOC1 could also be shown in biopsies of cervical cancer specimens. PCR-based promoter methylation analysis revealed a significant association between promoter methylation and the loss of LDOC1 expression, which could be reverted by DNA methyltransferase inhibitors. This indicates that silencing of LDOC1 is a frequent event in cervical cancer and may be of interest as a molecular marker in cervical cancer.
Li Z, Barron S, Hong W, et al. Surveillance for recurrent cancers and vaginal epithelial lesions in patients with invasive cervical cancer after hysterectomy: are vaginal cytology and high-risk human papillomavirus testing useful? Am J Clin Pathol. 2013; 140(5):708-14 [PubMed] Related Publications
OBJECTIVES: To examine whether women who have had a hysterectomy for cervical cancer may be at an increased risk of vaginal epithelial lesions. METHODS: We studied 147 patients with invasive cervical carcinoma (76 squamous cell carcinomas [SCCs], 60 adenocarcinomas [ADCs], and 11 adenosquamous cell carcinomas) who were treated by hysterectomy and had vaginal pathologic follow-up for a mean period of 43.3 months. RESULTS: Of the patients, 15.0% (22/147) developed vaginal intraepithelial neoplasia (VAIN) or recurrence after hysterectomy, including two recurrent carcinomas and eight high-grade VAINs. More important, these high-grade VAINs or recurrent carcinomas were detected only in patients with cervical SCC within the first two years after hysterectomy but not in patients with cervical ADC. Eleven (23.4%) of 47 patients had at least one positive high-risk human papillomavirus (hrHPV) testing result during the follow-up period, and VAIN was detected in 54.5% (6/11) of patients with an hrHPV-positive result compared with 16.7% (6/36) with an hrHPV-negative result. CONCLUSIONS: Our results indicate that women with cervical cancer are at an increased risk of VAIN besides recurrence, and women with cervical SCC are more prone to high-grade VAIN/recurrence, especially within the first two years after hysterectomy. The significantly increased detection rate of VAINs/recurrence in the hrHPV-positive group suggests vaginal cytology and HPV cotesting might be the preferred method for surveillance in these women.
Lee YY, Park W, Huh SJ, et al. Platinum-based combination chemotherapy vs. weekly cisplatin during adjuvant CCRT in early cervical cancer with pelvic LN metastasis. Anticancer Res. 2013; 33(10):4675-81 [PubMed] Related Publications
AIM: Adjuvant concurrent chemoradiation (CCRT) should be considered in surgically-treated patients with early-stage cervical cancer (ECC) who exhibit pelvic lymph node (LN) metastasis. Platinum-based chemotherapy is usually recommended during adjuvant CCRT, however, it is unclear which regimen has better prognostic outcomes. PATIENTS AND METHODS: We reviewed the electronic medical records to find patients with primary ECC (FIGO stages IB-IIA) who underwent type III radical hysterectomy and adjuvant CCRT due to pelvic LN metastasis at the Samsung Medical Center, Sungkyunkwan University School of Medicine in Seoul, Korea, from November 1997 to September 2007. RESULTS: Among 75 patients, 34 received weekly cisplatin. Combination chemotherapy was performed without consolidation in 21 patients and with consolidation in 20 patients. The mean follow-up period was 59.0 months and the five-year survival rate was 84.4%. In multivariate analysis, combination chemotherapy with and without consolidation was associated with improved disease-free survival [hazard ratio (HR)=0.23, 95% confidence interval (CI)=0.06-0.88, p=0.032, and HR=0.29, 95% CI=0.09-0.91, p=0.034, respectively]; combination chemotherapy with consolidation significantly improved overall survival (HR=0.11, 95% CI=0.02-0.87, p=0.037) when compared to weekly cisplatin. CONCLUSION: We found that platinum-based combination chemotherapy during adjuvant CCRT after surgery promoted better survival than a weekly cisplatin regimen in ECC patients with pelvic LN metastasis.
Harima Y, Ikeda K, Utsunomiya K, et al. Apolipoprotein C-II is a potential serum biomarker as a prognostic factor of locally advanced cervical cancer after chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013; 87(5):1155-61 [PubMed] Related Publications
PURPOSE: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). METHODS AND MATERIALS: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization-time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. RESULTS: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). CONCLUSION: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.
Clivio A, Kluge A, Cozzi L, et al. Intensity modulated proton beam radiation for brachytherapy in patients with cervical carcinoma. Int J Radiat Oncol Biol Phys. 2013; 87(5):897-903 [PubMed] Related Publications
PURPOSE: To evaluate intensity modulated proton therapy (IMPT) in patients with cervical cancer in terms of coverage, conformity, and dose-volume histogram (DVH) parameters correlated with recommendations from magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS: Eleven patients with histologically proven cervical cancer underwent primary chemoradiation for the pelvic lymph nodes, the uterus, the cervix, and the parametric region, with a symmetric margin of 1 cm. The prescription was for 50.4 Gy, with 1.8 Gy per fraction. The prescribed dose to the parametria was 2.12 Gy up to 59.36 Gy in 28 fractions as a simultaneous boost. For several reasons, the patients were unable to undergo brachytherapy. As an alternative, IMPT was planned with 5 fractions of 6 Gy to the cervix, including the macroscopic tumor with an MRI-guided target definition, with an isotropic margin of 5 mm for planning target volume (PTV) definition. Groupe-Europeen de Curietherapie and European society for Radiotherapy and Oncology (GEC-ESTRO) criteria were used for DVH evaluation. Reference comparison plans were optimized for volumetric modulated rapid arc (VMAT) therapy with the RapidArc (RA). RESULTS: The dose to the high-risk volume was calculated with α/β = 10 with 89.6 Gy. For IMPT, the clinical target volume showed a mean dose of 38.2 ± 5.0 Gy (35.0 ±1.8 Gy for RA). The D98% was 31.9 ± 2.6 Gy (RA: 30.8 ± 1.0 Gy). With regard to the organs at risk, the 2Gy Equivalent Dose (EQD2) (α/β = 3) to 2 cm(3) of the rectal wall, sigmoid wall, and bladder wall was 62.2 ± 6.4 Gy, 57.8 ± 6.1 Gy, and 80.6 ± 8.7 Gy (for RA: 75.3 ± 6.1 Gy, 66.9 ± 6.9 Gy, and 89.0 ± 7.2 Gy, respectively). For the IMPT boost plans in combination with external beam radiation therapy, all DVH parameters correlated with <5% risk for grades 2 to 4 late gastrointestinal and genitourinary toxicity. CONCLUSION: In patients who are not eligible for brachytherapy, IMPT as a boost technique additionally to external beam radiation therapy provides good target coverage and conformity and superior DVH parameters, compared with recommendations to MRI-guided brachytherapy. For selected patients, IMPT might be a valid alternative to brachytherapy and also superior to reference VMAT plans.
de Jonge M, Busecke G, Heinecke A, Bettendorf O Human papillomavirus genotype distribution in cytologically screened women from northwest Germany. Acta Cytol. 2013; 57(6):591-8 [PubMed] Related Publications
INTRODUCTION: In this study, we evaluate the distribution of 24 human papillomavirus (HPV) genotypes in a cohort of 3,381 cytologically screened women from a rural area of northwest Germany, in correlation to cytological diagnoses and histological outcomes. MATERIALS AND METHODS: We present a retrospective study in which the HPV-genotyping results of women who attended the German cervical screening program were correlated to cytological diagnosis and histological outcome. RESULTS: HPV genotyping showed marked differences among cervical lesions. Although HPV-51 was common in all cervical lesions, it was rarely detected as single-type HPV infection in high-grade cervical intraepithelial neoplasia (CIN)3 (2/118 cases). HPV-16 and 18 were more common in CIN3 (57.6%) than in CIN2 (21.8%), but they were absent in 42.4% of all CIN3 lesions in our cohort. DISCUSSION: Our data show that HPV-16, HPV-31, HPV-51, HPV-53 and HPV-42 are the most prevalent HPV types in the different cervical lesions in this region of northwest Germany. HPV genotyping has been shown to be a powerful tool to triage atypical squamous cells of undetermined significance lesions. Considering the observed heterogeneity of HPV types in CIN2, it could also be useful to triage CIN2+ lesions. Our results underline the usefulness of a morphologically controlled screening program with HPV genotyping as a powerful additional tool.
Azara CZ, Manrique EJ, Alves de Souza NL, et al. External quality control of cervical cytopathology: interlaboratory variability. Acta Cytol. 2013; 57(6):585-90 [PubMed] Related Publications
OBJECTIVE: To compare the variability of screening tests held at laboratories with the Unit for External Quality Control (UEQC), checking the frequency of cases that were discordant, false-positive, false-negative, unsatisfactory or that had a delay in clinical management and diagnostic agreement. MATERIALS AND METHODS: The study analyzed 10,053 screening tests from January 2007 to December 2008, including all positive cases, all those that fall under unsatisfactory and at least 10% of negative screening tests. The magnitude of the agreement was analyzed using the kappa coefficient. RESULTS: Out of the 10,053 cases analyzed, 7.59% were considered disagreeing, and it was estimated that 1.1% were false-negative. There was a delay in the clinical procedure regarding 2.44% cases. There were 2.82% of cases identified as false-positive and 1.24% as unsatisfactory. The diagnostic agreement was excellent (kappa = 0.81). The agreement of most laboratories concerning screening tests was classified as very good. The agreement of the sample adequacy was reasonable (kappa = 0.30) and the agreement regarding the representation of epithelia was considered excellent. CONCLUSION: Most laboratories showed very good agreement; however, it is worthy of note that to establish the standardization of diagnostic criteria, and enhance the accuracy of screening and improve the quality of cytopathology test results, it is necessary to perform external quality control.