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Cervical Cancer

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.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Human Papillomavirus (HPV), Vaccination, and Cervical Cancer
Cervical Cancer Screening (including the PAP smear test)
Gynacological Cancers

Information Patients and the Public (22 links)

Information for Health Professionals / Researchers (12 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Botha MH, van der Merwe FH, Snyman LC, Dreyer G
The vaccine and cervical cancer screen (VACCS) project: acceptance of human papillomavirus vaccination in a school-based programme in two provinces of South Africa.
S Afr Med J. 2015; 105(1):40-3 [PubMed] Related Publications
BACKGROUND: The incidence of cervical cancer in South Africa (SA) remains high, and the current screening programme has had limited success. New approaches to prevention and screening tactics are needed.
OBJECTIVES: To investigate acceptance of school-based human papillomavirus (HPV) vaccination, as well as the information provided, methods of obtaining consent and assent, and completion rates achieved.
METHODS: Information on cervical cancer and HPV vaccination was provided to 19 primary schools in Western Cape and Gauteng provinces participating in the study. Girls with parental consent and child assent were vaccinated during school hours at their schools.
RESULTS: A total of 3 465 girls were invited to receive HPV vaccine, of whom 2 046 provided written parental consent as well as child assent. At least one dose of vaccine was delivered to 2 030 girls (99.2% of the consented cohort), while a total of 1 782 girls received all three doses. Sufficient vaccination was achieved in 91.6% of the vaccinated cohort. Of all invited girls, 56.9% in Gauteng and 50.7% in the Western Cape were sufficiently vaccinated.
CONCLUSION: This implementation project demonstrated that HPV vaccination is practical and safe in SA schools. Political and community acceptance was good, and positive attitudes towards vaccination were encountered. During the study, which mimicked a governmental vaccine roll-out programme, high completion rates were achieved in spite of several challenges encountered.

Silva-Meléndez PE, Escobar PF, Héctor Silva, et al.
Small cell carcinoma of the uterine cervix: a case report and literature review.
Bol Asoc Med P R. 2015 Jan-Mar; 107(1):55-7 [PubMed] Related Publications
Small cell carcinoma of the uterine cervix is a rare and aggressive extra-pulmonary variant of small cell tumors. This carcinoma of the cervix comprises less than 5% of all cervical carcinomas and is know to be highly undifferentiated. It is associated with a poor prognosis and characterized by premature distant nodal involvement. The survival rate at all stages ranges from 17% to 67%. We describe the case of a 41 year old female patient with a rare, and aggressive, clinical stage IB1 small cell neuroendocrine carcinoma of the cervix. The goal of this case report is to describe this rare pathology and contribute information to the scant available data.

Beaber EF, Kim JJ, Schapira MM, et al.
Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.
J Natl Cancer Inst. 2015; 107(6):djv120 [PubMed] Related Publications
General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites.

Wang S, Sun H, Jia Y, et al.
Association of 42 SNPs with genetic risk for cervical cancer: an extensive meta-analysis.
BMC Med Genet. 2015; 16:25 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: A large number of single nucleotide polymorphisms (SNPs) associated with cervical cancer have been identified through candidate gene association studies and genome-wide association studies (GWAs). However, some studies have yielded different results for the same SNP. To obtain a more comprehensive understanding, we performed a meta-analysis on previously published case-control studies involving the SNPs associated with cervical cancer.
METHODS: Electronic searches of PubMed and Embase were conducted for all publications about the association between gene polymorphisms and cervical cancer. One-hundred and sixty-seven association studies were included in our research. For each SNP, three models (the allele, dominant and recessive effect models) were adopted in the meta-analysis. For each model, the effect summary odds ratio (OR) and 95% CI were calculated. Heterogeneity between studies was evaluated by Cochran's Q test. If the p value of Q test was less than 0.01, a random effect model was used; otherwise, a fixed effect model was used.
RESULTS: The results of our meta-analysis showed that: (1) There were 8, 2 and 8 SNPs that were significantly associated with cervical cancer (P < 0.01) in the allele, dominant and recessive effect models, respectively. (2) rs1048943 (CYP1A1 A4889G) showed the strongest association with cervical cancer in the allele effect model (1.83[1.57, 2.13]); in addition, rs1048943 (CYP1A1 A4889G) had a very strong association in the dominant and recessive effect model. (3) 15, 11 and 10 SNPs had high heterogeneity (P < 0.01) in the three models, respectively. (4) There was no published bias for most of the SNPs according to Egger's test (P < 0.01) and Funnel plot analysis. For some SNPs, their association with cervical cancer was only tested in a few studies and, therefore, might have been subjected to published bias. More studies on these loci are required.
CONCLUSION: Our meta-analysis provides a comprehensive evaluation of cervical cancer association studies.

Chacko S
Effect of structured teaching programme on VIA test for early detection and diagnosis of cervical cancer.
Nurs J India. 2014 Sep-Oct; 105(5):221-4 [PubMed] Related Publications
The conceptual framework of the study, undertaken in select health centres of New Delhi, was based on General System Model. The research approach was evaluative with one group pre-test and post-test design. The study population comprised of Community Health Workers working in selected centres in Najafgarh, Delhi. Purposive sampling technique was used to select a sample of 30 Community Health Workers. A structured knowledge questionnaire was developed to assess the knowledge of subjects. A Structured Teaching Programme was developed to enhance the knowledge of Community Health Workers. Pre-test was given on day 1 and Structured Teaching Programme administered on same day. Post-test was conducted on day 7. Most of the Community Health Workers were in the age group of 21-30 years with academic qualification up to Higher Secondary level. Maximum Community Health Workers had professional qualification as ANM/MPHW (female). Majority of the Community Health Workers had experience up to 5 years. Initially there was deficit in scores of knowledge of Community Health Workers regarding Visual Inspection with Acetic Acid (VIA) test. Mean post-test knowledge scores of Community Health Workers were found to be signifi- cantly higher than their mean pre-test knowledge score. The Community Health Workers after expo- sure to Structured Teaching Programme gained a significant positive relationship between post-test knowledge scores. The study reveals the efficacy of Structured Teaching Programme in enhancing the knowledge of Community Health Workers regarding VIA test and a need for conducting a regular and well planned health teaching programme on VIA test for improving their knowledge on VIA test for the early detection and diagnosis of cervical cancer.

Lin Y, Li H, Chen Z, et al.
Correlation of histogram analysis of apparent diffusion coefficient with uterine cervical pathologic finding.
AJR Am J Roentgenol. 2015; 204(5):1125-31 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to investigate the application of histogram analysis of apparent diffusion coefficient (ADC) in characterizing pathologic features of cervical cancer and benign cervical lesions.
SUBJECTS AND METHODS: This prospective study was approved by the institutional review board, and written informed consent was obtained. Seventy-three patients with cervical cancer (33-69 years old; 35 patients with International Federation of Gynecology and Obstetrics stage IB cervical cancer) and 38 patients (38-61 years old) with normal cervix or cervical benign lesions (control group) were enrolled. All patients underwent 3-T diffusion-weighted imaging (DWI) with b values of 0 and 800 s/mm(2). ADC values of the entire tumor in the patient group and the whole cervix volume in the control group were assessed. Mean ADC, median ADC, 25th and 75th percentiles of ADC, skewness, and kurtosis were calculated. Histogram parameters were compared between different pathologic features, as well as between stage IB cervical cancer and control groups.
RESULTS: Mean ADC, median ADC, and 25th percentile of ADC were significantly higher for adenocarcinoma (p = 0.021, 0.006, and 0.004, respectively), and skewness was significantly higher for squamous cell carcinoma (p = 0.011). Median ADC was statistically significantly higher for well or moderately differentiated tumors (p = 0.044), and skewness was statistically significantly higher for poorly differentiated tumors (p = 0.004). No statistically significant difference of ADC histogram was observed between lymphovascular space invasion subgroups. All histogram parameters differed significantly between stage IB cervical cancer and control groups (p < 0.05).
CONCLUSION: Distribution of ADCs characterized by histogram analysis may help to distinguish early-stage cervical cancer from normal cervix or cervical benign lesions and may be useful for evaluating the different pathologic features of cervical cancer.

Yang L, He Z, Huang XY, et al.
Prevalence of human papillomavirus and the correlation of HPV infection with cervical disease in Weihai, China.
Eur J Gynaecol Oncol. 2015; 36(1):73-7 [PubMed] Related Publications
OBJECTIVE: This study investigates the human papillomavirus (HPV) infection rate in female genital tracts, as well as the HPV genotype distribution and HPV correlation with cervical disease in Weihai, Shandong Province, China.
MATERIALS AND METHODS: A random sample of 9,460 volunteers was simultaneously screened using gene chips and examined by ThinPrep liquid-based cytology test (TCT). Cervical biopsy samples were collected from women with positive HPV-DNA and abnormal TCT for pathological diagnosis.
RESULTS: The overall HPV prevalence was 6.93% (656 of 9,460). A total of 753 subjects were infected with HPV subtypes (including multiple HPV infections). Of those with infections, 688 were infected with high-risk (HR) types (91.37%), and 65 were infected with low-risk subtypes (8.63%). The single-infection rate was 63.1%.The prevalence rates of HPV in women aged 20 to 39 years and 40 to 59 years were 7.29% and 6.71%, respectively. The most common genotype was HPV16. The HR genotypes were associated with cervical diseases such as atypical squamous cells of undetermined significance (ASCUS) (37.9%), atypical squamous cells high grade (ASC-H) (42.5%), low grade squamous intraepithelial lesion (LSIL) (50%), and high grade squamous intraepithelial lesion HSIL (66.7%). Cervical biopsy results show that the HPV detection rate increased in the following biopsy samples: cervical intraepithelial neoplasia (CIN) I (74.11%), CIN II (84.31%), CIN III (90.32%), and squamous-cell carcinoma (SCC) (100%).
CONCLUSIONS: The HPV infection rate with associated cervical disease in Weihai is equal to those in foreign countries but is lower than the average rate in China. The prevalence of HPV was higher in young people. The most common HPV genotype was 16, followed by 52 and 58. HR HPV is the most probable infection factor for cervical diseases.

Zhou WQ, Sheng QY, Sheng YH, et al.
Expressions of survivin, P16(INK4a), COX-2, and Ki-67 in cervical cancer progression reveal the potential clinical application.
Eur J Gynaecol Oncol. 2015; 36(1):62-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To explore the significance of survivin, P16(INK4a), COX-2, and Ki-67 expressions for prediction of cervical cancer progression.
MATERIALS AND METHODS: A retrospective study was performed in 129 cases including 24 squamous carcinoma of the cervix (SCC), 70 cervical intraepithelial neoplasias (CIN), 15 cervical condyloma acuminatum (CCA), ten chronic cervicitis (CC), and ten normal cervix (NC). Protein expressions were evaluated using immunohistochemistry.
RESULTS: Survivin, P16(INK4a); COX-2, and Ki-67 were highly expressed in SCC and CIN compared with others. Their expression rates were gradually increased in CIN I, CIN II, CIN III, and SCC groups, showing 72.00%, 88.00%, 90.00%, and 95.83% for P16(INK4a), 68.00%, 84.00%, 95.00% and 100.00% for COX-2, 76.00%, 96.00%, 100.00%, and 100.00 for Ki-67, respectively. There were significant correlations between survivin and P16(INK4a), COX-2, Ki-67, as well as P16(INK4a) and Ki-67.
CONCLUSION: Survivin, P16(INK4a), COX-2 and Ki-67 play critical roles for development and progression of cervical cancer.

Kerimoglu OS, Pekin A, Yilmaz SA, et al.
Pyometra in elderly post-menopausal women: a sign of malignity.
Eur J Gynaecol Oncol. 2015; 36(1):59-61 [PubMed] Related Publications
PURPOSE: To describe the clinical and histopathological characteristics of 12 patients with pyometra and highlight the increased incidence of gynecological malignancy in these patients.
MATERIALS AND METHODS: The authors examined the medical records of 12 patients with pyometra, who were treated between 2009 and 2013.
RESULTS: All patients were post-menopausal, and their mean age was 70.83 ± 6.978 years (min = 61, max = 82). To remove purulent fluid via dilation and because of the probability of malignancy, three patients (25%) underwent cervical biopsy and endometrial curettage; the other nine patients (75%) underwent curettage alone, with suitable antibiotic therapy. Of the 12 patients, nine (75%) had gynecologic malignancy [(endometrial cancer, n = 5, 41.6%), (cervical cancer, n = 3, 25%), (uterine leiomyosarcoma, n = 1, 8.3%)]. In three (25%) patients, the cause of pyometra was benign pathologies, among which the most common were leiomyomas (n = 2, 66.6%).
CONCLUSION: Pyometra diagnosed during the post-menopausal period should be considered a complication caused by gynecological malignancy until proven otherwise.

Li Y, Wang X, Li J, Ding W
Combination therapy of liposomal paclitaxel and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer.
Eur J Gynaecol Oncol. 2015; 36(1):54-8 [PubMed] Related Publications
OBJECTIVES: To investigate the efficacy and toxicities of combination therapy of liposomal paclitaxel and cisplatin as neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer.
MATERIALS AND METHODS: The authors retrospectively reviewed the clinical records of patients with cervical cancer who received NACT with liposomal paclitaxel and cisplatin at Sun Yat-sen University Cancer Center from April 1, 2008 to December 31, 2012. Liposomal paclitaxel and cisplatin was administrated intravenously at a dose of 175 mg/m2 and 75 mg/m2, respectively.
RESULTS: The total response rate was 86.1% (62/72) including a complete response and partial response rate of 27.8% (20/72) and 58.3% (42/72), respectively. Stable disease was observed in 12.5% (9/72) of patients and progressive disease in 1.4% (1/72). Hematological toxicities were the major dose-limiting toxicities. Grade 3/4 neutropenia and anemia developed in 18.1% (13/72) and 6.9% (5/72) of patients, respectively. Peripheral neuropathy occurred in 6.9% (5/72) of patients (all grade 1).
CONCLUSION: The study findings support further evaluation of liposomal paclitaxel with cisplatin as an additional chemotherapy regimen which may be efficacious and tolerable in the NACT of cervical cancer.

Andrikopoulou M, Salakos N, Deligeoroglou E, et al.
The role of mTOR signaling pathway in premalignant and malignant cervical lesions.
Eur J Gynaecol Oncol. 2015; 36(1):36-43 [PubMed] Related Publications
PURPOSE OF THE STUDY: Aberrant activation of the Akt/mTOR/pS6 signaling pathway has been identified in various types of cancer and is under investigation in cervical cancer. The purpose of this study was to assess the expression of the phosphorylated/activated forms of Akt (upstream molecule), 4E-BP1 and pS6 (downstream molecules) in biopsy samples of cervical low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), and squamous cell carcinoma (Ca) compared to normal cervical epithelium.
MATERIAL AND METHODS: The study included 38 cases diagnosed as LSIL, 31 cases as HSIL, 29 cases as Ca, and eight control cases from normal cervix. Immunohistochemistry was used to assess the expression of pAkt, p4E-BP1 and pS6.
RESULTS: Statistical analysis revealed significant differences between HSIL and Ca groups compared to controls regarding intensity, positivity, and total scores for all three molecules (p < 0.001). A trend for higher expression with increasing grade of dysplasia was demonstrated.
CONCLUSION: These results strongly support the view that the mTOR signaling pathway is involved in cervical carcinogenesis.

Cho SH, Lim JY, Kim SN, et al.
The prognostic significance of pretreatment [18F]FDG-PET/CT imaging in patients with uterine cervical cancer: preliminary results.
Eur J Gynaecol Oncol. 2015; 36(1):30-5 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To evaluate the prognostic significance of positron emission tomography/computed tomography (PET/CT) in patients diagnosed with cervical cancer.
MATERIALS AND METHODS: Patients with cervical cancer in FIGO Stages IB1 to IVB were imaged with PET/CT prior to treatment during one of the staging work-ups. The patients were observed for a median of 31.4 months (range, six to 89 months) after the initial treatment. The standardized uptake value (SUV) max of the primary cervical tumor mass was compared with the prognostic factors. RESULTs: A total of 81 patients who were primarily treated with radical hysterectomy (RH, n = 45) or concurrent chemoradiation (CCRT, n = 36) were analyzed. Multivariate analysis indicated that larger tumor size (> 4 cm, OR 8.694, 95% CI, 1.638-46.146), deep stromal invasion (≥ 1 cm, OR 7.249, 95% CI, 1.141-46.039) by the primary tumor, and pathologically confirmed pelvic lymph node involvement (positive, OR 14.586, 95% CI, 2.072-102.674) were significantly associated with recurrence after treatment. However, pretreatment SUVmax was not a significant independent predictor of disease recurrence (OR 1.058, 95% CI, 0.255-4.398).
CONCLUSION: [18F]Fluorodeoxyglucose (FDG) uptake by the primary tumor showed a significant association with several risk factors that have been identified as treatment predictors. However, a high pretreatment SUVmax was not predictive of recurrence in uter- ine cervical cancer patients.

Shou H, Chen Y, Chen Z, et al.
Laparoscopic ovarian transposition in young women with cervical squamous cell carcinoma treated by primary pelvic irradiation.
Eur J Gynaecol Oncol. 2015; 36(1):25-9 [PubMed] Related Publications
OBJECTIVE: To report the authors' experience with laparoscopic ovarian transposition and ovarian function preservation in young women with cervical squamous cell carcinoma treated by primary pelvic irradiation.
MATERIALS AND METHODS: Twenty-seven premenopausal patients were treated with radiotherapy for a cervical squamous cell carcinoma. Laparoscopic ovarian transposition to paracolic gutters with uterine conservation with pelvic common iliac lymph node and para-aortic lymph node sampling were performed in ten patients at the same time of laparoscopic ovarian transposition. Preservation of ovarian function was assessed by patients' symptoms and serum follicle-stimulating hormone level.
RESULTS: Bilateral or unilateral laparoscopic ovarian transposition was performed in 27 patients: 22 cases Stage IIB, one case Stage IIIA, and four cases Stage IIIB. No immediate intraoperative or postoperative complications were observed. Two of the ten patients were confirmed by lymph node metastases. One patient was lost to follow-up. Ovarian preservation was achieved in 18 (69.2%) of 26 patients. No patient was detected with ovarian metastasis at follow-up.
CONCLUSIONS: Laparoscopic ovarian transposition is a safe and effective procedure for preserving ovarian function. This procedure may be considered in premenopausal women who need to undergo pelvic irradiation for cervical squamous cell carcinoma, especially for those less than 40 years of age. Otherwise, para-aortic lymph node or common iliac lymph nods sampling at the same time of laparoscopic ovarian transposition may preferably guide radiation therapy.

Kavallaris A, Zygouris D, Dafopoulos A, et al.
Nerve sparing radical hysterectomy in early stage cervical cancer. Latest developments and review of the literature.
Eur J Gynaecol Oncol. 2015; 36(1):5-9 [PubMed] Related Publications
BACKGROUND: Cervical cancer is the second most common malignancy of the female genital tract worldwide. Radical hysterectomy with pelvic lymphadenectomy exemplifies the treatment of choice for early stage disease, whereas even if it is performed by gynaecologist-oncologist, still has the drawback of significant postoperative morbidity, especially for urinary bladder function. Nerve-sparing radical hysterectomy (NSRH) is a technique in which the neural part of the cardinal ligament which encloses the inferior hypogastric plexus, as well as the bladder branch (distal part of the plexus), remains intact. By this way, the bladder's innervation is safe and its functional recovery is more rapid. There is sufficient data to support the feasibility of the technique via laparotomy and laparoscopy, as well as the effectiveness related to the postoperative bladder dysfunction compared to conventional radical hysterectomy. On the other hand, the evidence related to survival outcomes is weak and derives from non-randomized trials. However, the low rate of local relapses after NSRH in early stage disease (IA2-IB1) with tumor diameter less than two cm makes the procedure suitable for this group of patients.
CONCLUSION: According to the current evidence NSRH seems to be a suitable technique for gynaecologist-oncologist familiar with the method in early stage cervical cancer. It is a technique which improves significantly postoperative bladder recovery and the patients' quality of life (QoL), without compromising the oncological standard.

Knegt Y
Audit of cervical cancer screening and colposcopy attendance in rural South Africa.
Afr J Reprod Health. 2014; 18(4):70-8 [PubMed] Related Publications
Women in developing countries generally lack access to cervical cancer preventive services. An audit was performed in rural South Africa to test the hypothesis that women do not follow (pre-)cancerous cervical disease treatment sufficiently, to understand the possible reasons for this non-attendance behavior, and to evaluate other published diagnostic and treatment initiatives. Based on Pap smear and colposcopy attendance data, including age, HIV status, month of attendance, and cervical intraepithelial neoplasia (CIN) staging, relatively few patients (54% of 928 patients) visited a colposcopy clinic following an abnormal Pap smear. Although these co-factors do not explain this high non-attendance rate, HIV status was an important co-factor; percentage-wise, HIV positivity correlated with a higher attendance rate. Screening methods that use mobile teams to successfully deliver cost-effective on-the-spot treatment warrant further attention.

Khan M, Sultana SS, Jabeen N, et al.
Visual inspection of cervix with acetic acid: a good alternative to pap smear for cervical cancer screening in resource-limited setting.
J Pak Med Assoc. 2015; 65(2):192-5 [PubMed] Related Publications
OBJECTIVE: To determine the diagnostic accuracy of visual inspection of cervix using 3% acetic acid as a screening test for early detection of cervical cancer taking histopathology as the gold standard.
METHODS: The cross-sectional study was conducted at Civil Hospital Karachi from July 1 to December 31, 2012 and comprised all sexually active women aged 19-60 years. During speculum examination 3% acetic acid was applied over the cervix with the help of cotton swab. The observations were noted as positive or negative on visual inspection of the cervix after acetic acid application according to acetowhite changes. Colposcopy-guided cervical biopsy was done in patients with positive or abnormal looking cervix. Colposcopic-directed biopsy was taken as the gold standard to assess visual inspection readings. SPSS 17 was used for statistical analysis.
RESULTS: There were 500 subjects with a mean age of 35.74 ± 9.64 years. Sensitivity, specifically, positive predicted value, negative predicted value of visual inspection of the cervix after acetic acid application was 93.5%, 95.8%, 76.3%, 99%, and the diagnostic accuracy was 95.6%.
CONCLUSION: Visual inspection of the cervix after acetic acid application is an effective method of detecting pre-invasive phase of cervical cancer and a good alternative to cytological screening for cervical cancer in resource-poor setting like Pakistan and can reduce maternal morbidity and mortality.

Thaxton L, Waxman AG
Cervical cancer prevention: immunization and screening 2015.
Med Clin North Am. 2015; 99(3):469-77 [PubMed] Related Publications
Both primary and secondary prevention of cervical cancer are now available. Immunizations against human papillomavirus (HPV) types 16 and 18 have the potential to prevent 70% of cancers of the cervix plus a large percentage of other lower anogenital tract cancers. Screening guidelines were recently changed to recommend cotesting with cytology plus an HPV test. The addition of HPV testing increases the sensitivity and negative predictive value of screening over the Papanicolaou (Pap) test alone.

Chen SJ, Kuo CC, Pan HY, et al.
Mechanistic basis of a combination D-penicillamine and platinum drugs synergistically inhibits tumor growth in oxaliplatin-resistant human cervical cancer cells in vitro and in vivo.
Biochem Pharmacol. 2015; 95(1):28-37 [PubMed] Related Publications
The platinum-based regimen is the front-line treatment of chemotherapy. However, development of platinum resistance often causes therapeutic failure in this disease. We previously have generated an oxaliplatin-resistant subline, named S3, from human cervical carcinoma SiHa cells, and its resistant phenotype was well-characterized. In the present study, we aimed to identify the novel therapeutic strategy by combining copper chelator D-penicillamine with oxaliplatin, and to elucidate the underlying mechanisms for overcoming oxaliplatin resistance. As the result, D-penicillamine exerted synergistic killing effects only in S3 cells when combined with oxaliplatin and cisplatin by using Chou-Talalay method. Further study showed that the amounts of platinum DNA adduct formed were positively correlated to the percentage of cell death in S3 cells when co-treated D-penicillamine with oxaliplatin and cisplatin. D-penicillamine promoted copper influx transporter hCtr1 expression through upregulation of Sp1. Sp1 overexpression induced p53 translocation from nucleus to cytosol and caused p53 degradation through ubiquitination, which subsequently suppressed the expression of the copper efflux transporter ATP7A. Importantly, co-treatment of cisplatin with D-penicillamine enhanced oxaliplatin-elicited antitumor effect in the oxalipatin-resistant S3 xenograft tumors, but not found in SiHa xenograft model. Notably, Mice received D-penicillamine alone or in combination of D-penicillamine ad oxalipatin, increased hCtrl protein level in S3 xenograft tumor, however, the protein level of ATP7A was decreased. Taken together, this study provides insight into that the co-manipulation of hCtrl and ATP7A by D-penicillamine could increase the therapeutic efficacy of platinum drugs in oxaliplatin resistant tumors, especially in resistant phenotype with downexpression of hCtrl and overexpression of ATP7A.

Marahatta Khanal R
Value of conventional cervical cytology as a screening test for cervical cancer.
Nepal Med Coll J. 2014; 16(1):63-7 [PubMed] Related Publications
This is a prospective study conducted in the department of Obstetrics and Gynecology of Nepal Medical College Teaching Hospital, Kathmandu, Nepal. The main Objective of the study is to see the value of opportunistic screening program for cervical pre-cancerous lesion for prevention of cervical cancer. It also aims to see how many cases can be picked up by such screening test and is it worth doing this test? We analysed 1751 cases of pap smear taken during almost 2 years period and found inflammatory smear being the predominant finding and it was found in reproductive age group. We had 1.14% cases of abnormal smear and 0.74% cases were proved by biopsy.

Ma XF, Zhang J, Shuai HL, et al.
IKKβ/NF-κB mediated the low doses of bisphenol A induced migration of cervical cancer cells.
Arch Biochem Biophys. 2015; 573:52-8 [PubMed] Related Publications
Cervical cancer is considered as the second most common female malignant disease. There is an urgent need to illustrate risk factors which can trigger the motility of cervical cancer cells. Our present study revealed that nanomolar concentration of bisphenol A (BPA) significantly promoted the in vitro migration and invasion of cervical cancer HeLa, SiHa, and C-33A cells. Further, BPA treatment increased the expression of metalloproteinase-9 (MMP-9) and fibronectin (FN) in both HeLa and SiHa cells, while did not obviously change the expression of MMP-2, vimentin (Vim) or N-Cadherin (N-Cad). BAY 11-7082, the inhibitor of NF-κB, significantly abolished BPA induced up regulation of FN and MMP-9 in cervical cancer cells. While the inhibitors of PKA (H89), ERK1/2 (PD 98059), EGFR (AG1478), or PI3K/Akt (LY294002) had no effect on the expression of either FN or MMP-9. BPA treatment rapidly increased the phosphorylation of both IκBα and p65, stimulated nuclear translocation, and up regulated the promoter activities of NF-κB. The BPA induced up regulation of MMP-9 and FN and activation of NF-κB were mediated by phosphorylation of IKKβ via PKC signals. Collectively, our study found for the first time that BPA stimulated the cervical cancer migration via IKK-β/NF-κB signals.

Barron S, Austin RM, Li Z, Zhao C
Follow-up outcomes in a large cohort of patients with HPV-negative LSIL cervical screening test results.
Am J Clin Pathol. 2015; 143(4):485-91 [PubMed] Related Publications
OBJECTIVES: Cervical screening guidelines now recommend repeat cotesting of patients aged 30 years and older having a human papillomavirus (HPV)-negative low-grade squamous intraepithelial lesion (LSIL) in 1 year as preferred management. Only limited follow-up data on patients with HPV-negative LSILs are available from routine US clinical practice settings.
METHODS: In total, 680 patients with Hybrid Capture 2 (Qiagen, Hinden, Germany) high-risk HPV-negative LSIL ThinPrep (Hologic, Marlborough, MA) results were identified. Patients' ages and histopathologic, cytologic, and HPV follow-up results were identified.
RESULTS: Among 680 patients with HPV-negative LSILs, 468 had follow-up within 1 year. During the study period, 14 (3.0%) of 468 had follow-up high-grade squamous intraepithelial lesion (HSIL) and 184 (39.3%) LSIL findings. No diagnoses of cervical carcinoma were documented. There were no significant follow-up differences between age groups. Of the 321 patients who had follow-up HPV testing, 271 (84.4%) had negative and 50 (15.6%) had positive HPV results.
CONCLUSIONS: This is the largest study documenting follow-up results for patients with HPV-negative LSIL results based on prevalent US FDA-approved co-testing methods from one collection vial. These data document that risk for follow-up HSILs in these patients is low and also that no cervical cancers were diagnosed. These findings support recent recommendations for repeat co-testing after 1 year as an appropriate option for patients with HPV-negative LSIL results.

Naumovic T, Miljus D, Djoric M, et al.
Mortality from cervical cancer in Serbia in the period 1991-2011.
J BUON. 2015 Jan-Feb; 20(1):231-4 [PubMed] Related Publications
PURPOSE: The aim of this study was to analyze trends of death rates for cervical cancer (CC) on territory of The Republic of Serbia in the period 1991-2011.
METHODS: In this descriptive epidemiological study, unpublished data of the Statistical Office of the Republic of Serbia were used for the analysis of mortality due to CC among women in Serbia, from 1991 to 2011. Three different types of rates were calculated: crude, age-specific and age-adjusted rates. The age-standardized rates were calculated by the direct method of standardization using the World Standard Population as standard. The trends were assessed by joinpoint linear regression analysis. An average annual percentage change (AAPC) and the corresponding 95% confidence intervals (CI) were computed for trends.
RESULTS: The average age-standardized CC mortality rate (ASCCMR) was 7.03 per 100,000. The lowest value of the ASCCMR was at the beginning of the observed period (6.05 per 100,000) and the highest was 8.17 per 100,000 in 2008. The age-adjusted CC mortality rates have been continuously and significantly increasing (AAPC=+0.7, 95% CI=0.3- 1.1, p<0.05). In all age groups we found increasing trends, except in the age group of 65-74 years.
CONCLUSION: Since ASCCMR has been steadily increasing during the period observed, reducing these rates is highly warranted. To achieve this target, an organized CC screening program is essential.

Liu S, Song L, Zhang L, et al.
miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1.
Biochem Biophys Res Commun. 2015; 459(4):679-85 [PubMed] Related Publications
Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3'-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity.

Camp EA, Prehn AW, Shen J, et al.
Factors associated with a lack of pap smear utilization in women exposed in utero to diethylstilbestrol.
J Womens Health (Larchmt). 2015; 24(4):308-15 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
BACKGROUND: Women in the 1940s-1960s were prescribed diethylstilbestrol (DES), a nonsteroidal estrogen, to prevent miscarriages, but the practice was terminated after it was discovered that the daughters so exposed in utero were at increased risk for developing clear cell adenocarcinoma (CCA) of the vagina or cervix at early ages. Pap smear screening is one of the principal methods used to identify tumor development and is necessary in this group of women to maintain their health. Currently, little is known about the factors associated with nonutilization of this screening tool in this high-risk population of women.
METHODS: National cohort data from the National Cancer Institute (NCI) DES Combined Cohort Follow-up Study during 1994, 1997, 2001, and 2006 were used to determine which factors were associated with Pap smear screening nonutilization in 2006 among DES-exposed and unexposed women. Self-reported questionnaire data from 2,861 DES-exposed and 1,027 unexposed women were analyzed using binary logistic regression models.
RESULTS: DES exposure, not having a previous gynecologic dysplasia diagnosis, lack of insurance, originating cohort, increasing age, and previous screening behavior were all factors associated with not reporting a Pap smear examination in the 2006 questionnaire, although college education reduced nonutilization.
CONCLUSIONS: Understanding which factors are associated with not acquiring a screening exam can help clinicians better identify which DES-exposed women are at risk for nonutilization and possibly tailor their standard of care to aid in the early detection of cervical and vaginal adenocarcinomas in this high-risk group.

Forhan SE, Godfrey CC, Watts DH, Langley CL
A systematic review of the effects of visual inspection with acetic acid, cryotherapy, and loop electrosurgical excision procedures for cervical dysplasia in HIV-infected women in low- and middle-income countries.
J Acquir Immune Defic Syndr. 2015; 68 Suppl 3:S350-6 [PubMed] Related Publications
BACKGROUND: Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain.
OBJECTIVE: We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC.
METHODS: A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality.
RESULTS: Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment.
CONCLUSIONS: Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women.

Bean-Mayberry B, Bastian L, Trentalange M, et al.
Associations between provider designation and female-specific cancer screening in women Veterans.
Med Care. 2015; 53(4 Suppl 1):S47-54 [PubMed] Related Publications
BACKGROUND: In 2010, the Department of Veterans Affairs Healthcare System (VA) implemented policy to provide Comprehensive Primary Care (for acute, chronic, and female-specific care) from designated Women's Health providers (DWHPs) at all VA sites. However, since that time no comparisons of quality measures have been available to assess the level of care for women Veterans assigned to these providers.
OBJECTIVES: To evaluate the associations between cervical and breast cancer screening rates among age-appropriate women Veterans and designation of primary-care provider (DWHP vs. non-DWHP).
RESEARCH DESIGN: Cross-sectional analyses using the fiscal year 2012 data on VA women's health providers, administrative files, and patient-specific quality measures.
SUBJECTS: The sample included 37,128 women Veterans aged 21 through 69 years.
MEASURES: Variables included patient demographic and clinical factors (ie, age, race, ethnicity, mental health diagnoses, obesity, and site), and provider factors (ie, DWHP status, sex, and panel size). Screening measures were defined by age-appropriate subgroups using VA national guidelines.
RESULTS: Female-specific cancer screening rates were higher among patients assigned to DWHPs (cervical cytology 94.4% vs. 91.9%, P<0.0001; mammography 86.3% vs. 83.3%, P<0.0001). In multivariable models with adjustment for patient and provider characteristics, patients assigned to DWHPs had higher odds of cervical cancer screening (odds ratio, 1.26; 95% confidence interval, 1.07-1.47; P<0.0001) and breast cancer screening (odds ratio, 1.24; 95% CI, 1.10-1.39; P<0.0001).
CONCLUSIONS: As the proportion of women Veterans increases, assignment to DWHPs may raise rate of female-specific cancer screening within VA. Separate evaluation of sex neutral measures is needed to determine whether other measures accrue benefits for patients with DWHPs.

Pornprasertpol A, Sereemaspun A, Sooklert K, et al.
Anticancer activity of selected Colocasia gigantia fractions.
J Med Assoc Thai. 2015; 98 Suppl 1:S98-106 [PubMed] Related Publications
The objective of this study is to investigate the anticancer potential of the extract of Colocasia gigantea C. gigantea), a plant member of the Araceae family. In the present study, we investigated the cytotoxic activity of C. gigantea extract on cervical cancer (Hela) and human white blood cells (WBC) in vitro. The authors then identified the bioactive ingredients that demonstrated cytotoxicity on tested cells and evaluated those bioactive ingredients using the bioassay-guided fractionation method. The results showed that not all parts of C. gigantea promote cytotoxic activity. The dichloromethane leaf fraction showed significant cell proliferation effect on Hela cells, but not on WBCs. Only the n-hexane tuber fraction (Fr. 1T) exhibited significant cytotoxicity on Hela cells (IC50 = 585 μg/ml) and encouraged WBC cell proliferation. From GC-Mass spectrometry, 4,22-Stigmastadiene-3-one, Diazoprogesterone, 9-Octadecenoic acid (Z)-, hexyl ester and Oleic Acid were the components of Fr 1T that demonstrated cytotoxic potential. In conclusion, C. gigantea's Fr 1T shows potential for cervical cancer treatment.

Thakur A, Gupta B, Gupta A, Chauhan R
Risk factors for cancer cervix among rural women of a hilly state: a case-control study.
Indian J Public Health. 2015 Jan-Mar; 59(1):45-8 [PubMed] Related Publications
In Himachal Pradesh, cancer cervix is a major public health problem since it ranks as the number one female cancer. A case-control study of 226 newly diagnosed, histopathologically confirmed cases of cancer cervix and equal number of matched controls was conducted at Regional Cancer Center, Himachal Pradesh during the period from July 2008 to October 2009 with the objective to study the common factors associated with cancer cervix. Univariate analysis identified 10 risk factors associated significantly with the disease. On multiple logistic regression, however, only seven risk factors were found to be associated significantly with the disease. These were: Age at birth of first child, spacing between two children, age at marriage, literacy, socioeconomic status, multiparity, and poor genital hygiene. Risk factors such as poor genital hygiene, age at birth of first child <19 years, early marriage, illiteracy, multiparity, and low socioeconomic status were highly prevalent in the study subjects and were found to be significantly associated with cancer cervix.

Wang LQ, Zhang Y, Yan H, et al.
MicroRNA-373 functions as an oncogene and targets YOD1 gene in cervical cancer.
Biochem Biophys Res Commun. 2015; 459(3):515-20 [PubMed] Related Publications
miR-373 was reported to be elevated in several tumors; however, the role of miR-373 in cervical cancer has not been investigated. In this study we aimed to investigate the role of miR-373 in tumorigenicity of cervical cancer cells in vivo and in vitro. The expression of miR-373 was investigated using real-time reverse transcription-polymerase chain reaction assay in 45 cervical specimens and cervical cancer cell lines. The role of miR-373 in tumorigenicity of cervical cancer cells was assessed by cell proliferation, colony formation in vitro as well as tumor growth assays in vivo with the overexpression of miR-373 or gene silencing. The functional target gene of miR-373 in cervical cancer cells was identified using integrated bioinformatics analysis, gene expression arrays, and luciferase assay. We founded that the expression of miR-373 is upregulated in human cervical cancer tissues and cervical carcinoma cell lines when compared to the corresponding noncancerous tissues. Ectopic overexpression of miR-373 in human cervical cancer cells promoted cell growth in vitro and tumorigenicity in vivo, whereas silencing the expression of miR-373 decreased the rate of cell growth. YOD1 was identified as a direct and functional target of miR-373 in cervical cancer cells. Expression levels of miR-373 were inversely correlated with YOD1 levels in human cervical cancer tissues. RNAi-mediated knockdown of YOD1 phenocopied the proliferation-promoting effect of miR-373. Moreover, overexpression of YOD1 abrogated miR-373-induced proliferation of cervical cancer cells. These results demonstrate that miR-373 increases proliferation by directly targeting YOD1, a new potential therapeutic target in cervical cancer.

Diao MK, Liu CY, Liu HW, et al.
Integrated HPV genomes tend to integrate in gene desert areas in the CaSki, HeLa, and SiHa cervical cancer cell lines.
Life Sci. 2015; 127:46-52 [PubMed] Related Publications
AIMS: The integration preferences of human papillomavirus (HPV) have been intensively studied and contested over recent years. To disclose the integration preferences of high-risk HPV in cervical cancer, HPV transcriptional sites and features in different cervical cancer cell lines were identified.
MAIN METHODS: In this study, three cervical cancer cell lines (CaSki, HeLa, and SiHa) were subjected for HPV genome status determination by amplification of papillomavirus oncogene transcripts (APOT) assay. The numbers of viral copies in human genomes and numbers of viral-human fusion mRNAs in three HPV-integrated cervical cancer cell lines were measured and analysed.
KEY FINDINGS: The results revealed that the gene desert region 8q24 of the HPV type 18 integrated HeLa cell line and the 13q21-22 region of the HPV type 16 integrated CaSki and SiHa cell lines were hotspots for HPV integration, and the numbers of viral copies in the human genomes of the three cell lines that we detected were not in accordance with those reported in previous studies.
SIGNIFICANCE: Integration of the HPV genome into the host cell chromosome suggests that persistent HPV infection is vital for malignant cell transformation and carcinogenesis. This study provides information to benefit health care professionals seeking more comprehensive and accurate diagnostics for HPV-related disease"? Please check, and amend as necessary.

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