Cervical Cancer
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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).

Wang Z, Zeng X, Ma Y, et al.
Antitumor efficiency of D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) nanoparticle-based delivery of docetaxel in mice bearing cervical cancer.
J Biomed Nanotechnol. 2014; 10(8):1509-19 [PubMed] Related Publications
Pharmaceutical nanotechnology holds potential in cancer chemotherapy. In this research, the docetaxel-loaded D-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-caprolactone-ran-lactide) (TPGS-b-(PCL-ran-PLA)) nanoparticles were prepared by a modified nanoprecipitation method and then the particle size, surface morphology, nanoparticle stability, in vitro drug release and cellular uptake of nanoparticles were characterized. Finally, we evaluated the therapeutic effects of nanoparticle formulation in comparison with Taxotere both in vitro and in vivo. The size of TPGS-b-(PCL-ran-PLA) nanoparticles was about 150 nm and much smaller than PCL nanoparticles (about 185 nm) and the absolute value of zeta potential was higher than PCL nanoparticles (16.49 mV vs. 13.17 mV). FESEM images further confirmed the morphology and size of nanoparticles. The drug-loaded nanoparticles were considered to be stable, showing no change in the particle size and surface charge during three-month storage of its aqueous solution. In vitro drug release of TPGS-b-(PCL-ran-PLA) nanoparticles was much faster than PCL and PCL-TPGS nanoparticles. The cumulative drug release of docetaxel-loaded TPGS-b-(PCL-ran-PLA), PCL-TPGS, and PCL NPs were 38.00%, 34.48% and 29.04%, respectively. TPGS-b-(PCL-ran-PLA) nanoparticles showed an obvious increase of cellular uptake. Due to the advantages of TPGS-b-(PCL-ran-PLA) nanoparticles, it could achieve significantly higher level of cytotoxicity in vitro and better inhibition effect of tumor growth on xenograft BALB/c nude mice tumor model than commercial Taxotere at the same dose (1.49-fold more effective). The TPGS-b-(PCL-ran-PLA) could be used as a novel and potential biodegradable polymeric material for nanoformulation in cervical cancer chemotherapy.

Related: Docetaxel

Penaranda E, Molokwu J, Hernandez I, et al.
Attitudes toward self-sampling for cervical cancer screening among primary care attendees living on the US-Mexico border.
South Med J. 2014; 107(7):426-32 [PubMed] Related Publications
BACKGROUND: Hispanic women living along the US border with Mexico have one of the highest cervical cancer mortality rates in the nation, owing in part to lower rates of screening. The barriers to screening in this population include lack of access to care and fear of and embarrassment about the pelvic examination. Screening for oncogenic or high-risk human papillomavirus during cervical cytology has been added to screening recommendations. A novel method for human papillomavirus testing is self-sampling, in which women collect their own cervicovaginal samples. There is lack of information about the acceptability of self-sampling as an alternative to cytology for cervical cancer screening in women living along the US-Mexico border.
METHODS: We conducted five focus groups with women between the ages of 30 and 65 who were primary care patients of clinics along the US-Mexico border. We used constructs from different health behavioral theories as a framework for the interview guide.
RESULTS: A total of 21 women participated in the focus groups, 80% of whom were Hispanic; mean age was 53.4 (standard deviation 7.9). More than one-third (38%) of the participants had not undergone a Papanicolaou test in the last 3 years. Women identified the perceived benefits of self-sampling as ease, convenience, practicability, less embarrassment, and need for child care as compared with a Papanicolaou test. The main barrier to self-sampling was concern about not performing the test correctly.
CONCLUSIONS: In this qualitative study, we found positive attitudes toward self-sampling among women living along the US border with Mexico. Further research is needed to evaluate interventions that address women's low levels of self-efficacy to perform the test and to evaluate the effectiveness of self-sampling in increasing cervical cancer screening rates.

Related: Cancer Screening and Early Detection USA

Kothari A
HPV vaccination: effects on cervical screening.
Nurs Times. 2014 Jun 11-17; 110(24):19-21 [PubMed] Related Publications
Uptake of cervical screening has declined slightly since the 1990s, and is generally lower among young women than older women. Although the human papillomavirus vaccination programme is successful, some girls are still not being vaccinated. In addition, the programme may have a negative impact on the uptake of cervical screening, as young women may not realise they are still vulnerable to cervical cancer after vaccination. Nurses should encourage girls and young women to take up both HPV vaccination and cervical screening.

Related: Cancer Screening and Early Detection

Reynolds D
Religiosity and parental acceptance of human papillomavirus (HPV) vaccine in 9-18 year-old girls.
J Christ Nurs. 2014 Jul-Sep; 31(3):172-7 [PubMed] Related Publications
The religious affiliation of parents/guardians may factor into the decision to accept human papillomavirus vaccine (HPV) vaccination for their 9- to 18-year-old girls but prior research findings are inconsistent on religious impact. This study assessed degree of religiosity and impact on HPV vaccination. No correlation was found between religiosity and vaccination status; however, significant correlations were found between religiosity and other assessed variables.

Related: USA

Porto MA, Habib PA
Viva Mulher: constructing a cervical cancer control program in Brazil.
Dynamis. 2014; 34(1):101-23 [PubMed] Related Publications
Through a number of isolated initiatives that began in the 1960s, Brazil accumulated knowledge and experience that in the late 1990s culminated in the implementation of the first nationwide public health action meant to coordinate health bodies and personnel from the federal, state, and municipal administrative levels to address a chronic degenerative disease. The main goal of this article is to analyze the process of construction of this public policy for cancer control in Brazil--more specifically, organized screening for the control of cervical cancer in the form of the Viva Mulher program. Our analytical approach relies on elements from the history of public policy and from the history of institutions, combining the use of documental sources, scientific literature, and interviews with managers involved in the process under study. Our analysis endeavors to show how and to what extent this national process incorporated the experiences of local projects and responded both to pressure from the social movement and to the country's political environment. It further shows how the new context, shaped by changes in the organization of the Brazilian health system, influenced this process.

Du CX, Li SQ, Wang AH, Wang Y
Significance of combined detection of p53 and FHIT in cervical carcinoma diagnosis.
Eur J Gynaecol Oncol. 2014; 35(3):298-300 [PubMed] Related Publications
PURPOSE: To explore the significance of combined detection of p53 genes and fragile histidine triad (FHIT) genes in cervical carcinoma.
MATERIALS AND METHODS: Specimens taken from 161 cases invasive carcinoma, 23 cases carcinoma in situ or cervical intraepithelial neoplasia III (CIN III), 74 cases CIN I - II, 25 cases normal cervical tissue, and 32 cases tumor-adjacent tissues were processed by immunohistochemistry to determine the expression of p53 and FHIT genes. The results of the combined detection were compared for clinical diagnostic value of cervical carcinoma diagnosis.
RESULTS: The p53 gene, FHIT gene and the two genes combined examination of cervical carcinoma diagnostic sensitivity were: 65.8% (121/184), 66.3% (122/184), 90.2% (166/184), respectively. There were no significant differences between the p53 gene and the FHIT gene detected (p > 0.05). Combined detection of the two gene were more sensitivity than single detection, the difference was significant (p < 0.001). Although diagnosis specificity had dropped somewhat, no significant statistical appeared (chi2 = 0.022, p > 0.05).
CONCLUSION: Combined detection of p53 genes and FHIT genes can increase the sensitivity diagnosis and specificity diagnosis for early cervical carcinoma and precancerous lesions has a positive meaning.

Tibúrcio MG, Pinheiro NM, Carboni Sde S, et al.
GTPases Rho distribution in intraepithelial and invasive neoplasias of the uterine cervix.
Eur J Gynaecol Oncol. 2014; 35(3):284-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To evaluate the distribution of GTPases RhoA, RhoB, and Cdc42 in cervical intraepithelial neoplasias (CIN) and invasive neoplasias of the uterine cervix.
MATERIALS AND METHODS: samples of neoplastic lesions of the uterine cervix of 44 patients were classified in: CIN I (n = 10), CIN II (n = 10), CIN III (n = 09), and invasive carcinoma (n = 15). Antibodies anti-RhoA, anti-RhoB, and anti-Cdc42 were used and staining was classified as: negative, mild, moderate, and intense positive.
RESULTS: When compared with dysplastic cells, superficial cells showed: higher expression of RhoB in CIN I (p = 0.0018), and lower expression of Cdc42 in CIN I (p = 0.0225). The authors observed higher expression of RhoA (p = 0.0002) and RhoB (p = 0.0046) in CIN dysplastic cells when compared with invasive carcinoma cells.
CONCLUSIONS: GTPases Rho may be involved with the regulation of biological processes, important to the progression of cervical neoplasias. Probably, RhoA is important for maintenance of cell differentiation and RhoB protects cells from malignant cervical neoplasia.

Related: CDC42 RHOA RHOB

Choi SD, Kim TH, Bae DH
Cervical intraepithelial neoplasia based on array comparative genomic hybridization.
Eur J Gynaecol Oncol. 2014; 35(3):270-3 [PubMed] Related Publications
Uterine cervical cancer is one of the most frequently observed malignant gynaecologic tumors. Carcinoma in situ or invasive cervical carcinoma develops from a low-grade intraepithelial lesion of the cervix over time. Human papillomavirus (HPV) is known to be a major contributing factor. With improvements in molecular genetic technologies, the authors attempted to identify the genomic changes associated with cervical precancerous lesions. In this study, changes in gene copy numbers were evaluated in five cases of severe uterine cervical dysplasia (HPV negative, two cases; HPV 16 and 18 positive only, three cases) by array comparative genomic hybridization (array CGH), and genes with copy number changes were compared between the two groups. Between the HPV positive and negative groups, only one gene was found to be upregulated more than 1.5 fold (3q23-q24), and no downregulated genes were identified. In conclusion, it is useful to evaluate genomic aberrations in cervical cancer using array CGH.

Related: CGH

Yin ZM, Yu AJ, Wu MJ, et al.
Prognostic factors and treatment comparison in small cell neuroendocrine cervical carcinoma.
Eur J Gynaecol Oncol. 2014; 35(3):259-63 [PubMed] Related Publications
OBJECTIVE: To determine the clinicopathologic factors associated with survival in small cell neuroendocrine cervical cancer (SCNEC) patients.
MATERIALS AND METHODS: The study was approved by the ethics committee of the hospital. The records of 64 SCNEC patients from 9,474 Chinese patients with cervical cancer at the Zhejiang Cancer Hospital were reviewed. Kaplan-Meier and Cox regression methods were used for analyses.
RESULTS: Of 64 patients, 47 had Stages I-IIA, 12 had Stages IIB-IVA, and five had Stage IV-B disease. A total of 81.25% underwent surgery, 89.1% received chemotherapy, 62.5% received radiation, 34.4% received neoadjuvant chemotherapy (NACT), and 34.4% received concurrent chemoradiation (CCRT). The median follow-up for surviving patients was 35.7 months (range: 0.5-160), and 29 (50%) of the 58 patients with Stages I-III had either disease recurrence or progression. The median time to first relapse was 10.5 months (range: 0-88.2). The five-year overall survival of patients in Stages I-IIA and IIB-IVB disease was 54.4% and 9.8%, respectively (p = 0.001). Women with early-stage (Stages IIBIIA) disease had median survival rates of 94 months compared with 21.4 months in the advanced-stage (Stages IIB-IVB) group. In univariate analysis, advanced-stage (p = 0.001), without radical surgery (p = 0.002) and deep stromal invasion (DSI) (p = 0.000) were considered poor prognostic factors. In a multivariable analysis, tumor size > four cm (p = 0.048), postoperative radiation (p = 0.038) for early-stage patients and the FIGO stage (p = 0.040) of disease in the overall population remained as independent prognostic factor of survival.
CONCLUSION: The FIGO stage was found to be an independent prognostic factor of SCNEC. In addition, tumor size > four cm and DSI was associated with poor survival. Postoperative radiation for early-stage patients may not improve survival. The role of primary and postoperative NACT or CCRT is unclear. Clinical trials are needed.

Tjalma WA
The ideal cervical cancer screening recommendation for Belgium, an industrialized country in Europe.
Eur J Gynaecol Oncol. 2014; 35(3):211-8 [PubMed] Related Publications
Cervical cancer should be a historical disease, why are we not succeeding! The prophylactic vaccination will reduce cervical cancer by almost 80% in Belgium. Cervical cancer screening should therefore remain in order to prevent the remaining 20%. The current used Pap cytology test misses 50% of all clinically significant precancers and cancers at the time of testing. The test should remain but the analysis should be altered. The screening should be modified based on our knowledge of human papillomavirus (HPV) as causal factor. Instead of looking for a cell abnormality, one should look for the presence of HPV. Then depending on the test, only two to ten percent of all relevant lesions are missed. The introduction of the vaccination should lead to the re-introduction of the screening based on HPV. This will not only lead to a considerable reduction in morbidity and mortality, allow longer screening intervals, but it will also be more cost-effective. More for less should be the driving force in cervical cancer screening if we want to be successful.

Related: Cancer Screening and Early Detection

Fröbe A, Jones G, Bokulić T, et al.
High-dose-rate brachytherapy and concurrent chemoradiotherapy followed by surgery for stage Ib-IIb cervical cancer: single institution experience.
Anticancer Res. 2014; 34(7):3861-6 [PubMed] Related Publications
BACKGROUND: There are still controversies about the benefit of surgery after concurrent radiochemotherapy (CRT) for locally advanced cervical cancer. The aim of this study was to evaluate toxicity, local tumor control and overall survival of surgery after CRT in stage IB-IIB cervical cancer.
PATIENTS AND METHODS: Between 2002 and 2008, 24 patients with stage IB-IIB cervical cancer were treated with external-beam radiotherapy concomitantly with chemotherapy. High-dose rate brachytherapy fractions were given once weekly. Radical hysterectomy was undertaken after a median of 42 days.
RESULTS: Overall survival at five years was estimated at 75% (95% confidence interval=52-88%) and sustained thereafter through to 8.9 years. No patient experienced local failure in the surgical bed. Postoperative complications were recorded in two patients.
CONCLUSION: Surgery after CRT in stage IB-IIB cervical cancer is safe and leads to better local control of the disease and overall survival.

Related: Brachytherapy

Nicolas F, Robert AL, Lavoué V, et al.
Ultrasound evaluation of cervical regeneration after LLETZ for cervical intraepithelial neoplasia: a prospective observational study.
Anticancer Res. 2014; 34(7):3799-805 [PubMed] Related Publications
OBJECTIVES: To assess cervical regeneration after large loop excision of the transformation zone (LLETZ) by ultrasound (US) measurements of cervical length (CL) before conization as well as in the postoperative short- and long-term and to identify factors affecting regeneration.
PATIENTS AND METHODS: This was a prospective observational study including patients under 45 years of age treated by LLETZ for Cervical Intraepithelial Neoplasia (CIN) with repeated measurements of CL by transvaginal US before and just after LLETZ, at 1 and 6 months postoperatively.
RESULTS: A total of 83 patients were enrolled, out of which 53 were included in the study. The mean CL was 28.6 mm (±5.7) preoperatively versus 18.3 mm (±4.2) after surgery; 21.8 mm (±4.4) at 1 month and 25.5 mm (±4.9) at 6 months. The mean cone length estimated by US was 10.3 mm (±3.4). The differences in CL before/after conization and CL after conization/at 6 months were statistically significant (p<0.0001). Cervical regeneration at 6 months was 71% (±20), statistically greater than regeneration at 1 month (32%, ±16) (p<0.0001).
DISCUSSION: Post-conization cervical tissue regeneration occurred with almost three quarters of the initial cervical length restored at 6 months. Further studies evaluating obstetric outcomes after LLETZ according to cervical regeneration might subsequently be used in clinical practice to identify high-risk pregnancies by pre- and postoperative US measurements of the cervical length. A rigorous assessment of CIN treatment risks and benefits remains essential when considering treating patients of childbearing age given a potential obstetric risk from conization.

Lee JW, Lee J, Moon EY
HeLa human cervical cancer cell migration is inhibited by treatment with dibutyryl-cAMP.
Anticancer Res. 2014; 34(7):3447-55 [PubMed] Related Publications
Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein1 (RAP1) GTPase that regulates various cellular functions including cell migration. Herein, we investigated whether cAMP-mediated PKA and EPAC1/RAP1 pathways differentially control HeLa cervical cancer cell migration. Although HeLa cell migration was reduced by dibutyryl-cAMP, we observed an increase in cAMP/PKA, cAMP/EPAC1/RAP1-GTPase, and RAC1-GTPase. HeLa cell migration and RAC1-GTPase were increased by treatment with 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cAMP analogue to activate EPAC-specific signaling pathways. When HeLa cells were treated with H-89, a PKA inhibitor, cell migration was enhanced but RAC1-GTPase was inhibited. In addition, cell migration induced by dibutyryl-cAMP was reversed but the activity of Rac1-GTPase was inhibited by H-89 treatment. Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. It also suggests that cAMP-mediated cancer cell migration was independent of RAC1-GTPase activation.

Meirovitz M, Gatt D, Dreiher J, Shaco-Levy R
Uterine cervix conization based on Pap smear results: the "see and treat" approach.
Isr Med Assoc J. 2014; 16(5):303-6 [PubMed] Related Publications
BACKGROUND: The "see and treat" approach, proceeding without a biopsy directly to uterine cervix conization in women diagnosed with high grade squamous intraepithelial lesion (HGSIL) on Pap smear, shortens the treatment duration, lessens patient anxiety, and reduces health care costs.
OBJECTIVES: To evaluate the level of diagnostic accuracy and the over-treatment rate in the "see and treat" versus conventional management of women diagnosed with HGSIL.
METHODS: We retrospectively reviewed all women with HGSIL who had undergone the "see and treat" approach during 2001-2011 at Soroka University Medical Center. Similar cohorts, who were managed conventionally with a cervical biopsy prior to the conization, served as a comparison group.
RESULTS: The study population consisted of 403 women: 72 (18%) had undergone the "see and treat" approach and 331 (82%) conventional management. The false positive rate was 11% for the "see and treat" group, compared to 6% for the conventional management group (P = 0.162). Similarly, no statistically significant difference was observed when comparing the positive predictive value (PPV) of high grade dysplasia diagnosed on Pap smear (PPV 88.9%) versus cervical biopsy (PPV 93.8%) (P = 0.204). Moreover, both the false positive rate and PPV remained similar in subgroups of patients, according to age, menopausal status, number of births, and colposcopy findings.
CONCLUSIONS: The accuracy level of HGSIL diagnosis on Pap smear is similar to that of high grade dysplasia on a cervical biopsy. We therefore recommend referring patients with HGSIL directly to conization. Skipping the biopsy step was not associated with significant over-treatment or other adverse effects.

Hung MC, Wu CL, Hsu YY, et al.
Estimation of potential gain in quality of life from early detection of cervical cancer.
Value Health. 2014; 17(4):482-6 [PubMed] Related Publications
OBJECTIVE: To estimate the lifetime gain in the health-related quality of life (HRQOL) from early detection of cervical cancer.
METHODS: A consecutive, cross-sectional sample of 421 patients with cervical cancer was administered the World Health Organization Quality of Life-brief version questionnaires. A nationwide sample of 22,543 patients with invasive cervical cancer (ICC) was collected from the national cancer registry for estimation of lifetime survival function from 1998 to 2007, which was further multiplied by the ratio of HRQOL score functions for patients with ICC and patients with carcinoma in situ (CIS), and summed up over lifetime to obtain expected relative-quality-adjusted survival. The difference between lifetime survival and the expected relative-quality-adjusted survival gives the expected total dissatisfied time during the life course.
RESULTS: In comparison with patients with CIS postconization, patients with ICC showed consistently lower scores in the physical and psychological domains and that of sexual life after adjustment for other risk factors. The expected years of life lost for an invasive cancer was 6.48 years using the general population as the reference cohort, while the durations of equivalent to living with a very dissatisfied HRQOL were 1.71 and 0.25 for the physical and psychological domains, respectively, and 1.47 years for sexual life. Validation of the extrapolation method based on a subcohort followed from the 6th to the 13th year shows a relative bias of 0.4%. Sensitivity analysis with 37,000 CIS cases as the reference cohort yields a similar result.
CONCLUSIONS: Early detection of cervical cancer not only avoids premature mortality but also prevents long-term living under lower HRQOL scores, including sexual life.

Related: Cancer Screening and Early Detection

Iliescu L, David L, Orban C, et al.
A rare case of ileal metastasis from cervical cancer.
Chirurgia (Bucur). 2014 May-Jun; 109(3):390-2 [PubMed] Related Publications
We present the case of a 70-year-old woman, with a history of radiation-treated and surgically- resected cervical cancer, who was admitted to our clinic for intermittent sub occlusive symptoms. CT scan revealed a liver nodule and intestinal obstruction. The patient underwent surgery for excision of suspected liver metastasis and resolution of intestinal obstruction.Intraoperatively an ileal tumour was found to be the cause of the obstruction. Anatomo-pathological findings were consistent with an ileal metastasis from the cervical cancer.The liver nodule was only an area of focal steatosis.

Mabuchi S, Matsumoto Y, Kawano M, et al.
Uterine cervical cancer displaying tumor-related leukocytosis: a distinct clinical entity with radioresistant feature.
J Natl Cancer Inst. 2014; 106(7) [PubMed] Related Publications
BACKGROUND: Tumor-related leukocytosis (TRL) is occasionally found in patients with nonhematopoietic malignancies. We investigated the clinical implication of TRL and individualized treatment for TRL-positive cervical cancer, as well as the underlying biological mechanism.
METHODS: Clinical data from 258 cervical cancer patients treated with definitive radiotherapy were analyzed to investigate the association between TRL and treatment outcome. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were used to examine the mechanisms responsible for TRL in cervical cancer, focusing on the role of tumor-derived granulocyte colony-stimulating factor (G-CSF) and myeloid-derived suppressor cells (MDSCs). All statistical tests were two-sided.
RESULTS: TRL was statistically significantly associated with younger age (Wilcoxon rank sum test, P = .03), larger tumor size (Wilcoxon rank sum test, P = .006), advanced clinical stage (χ(2) test, P = .01), and shorter overall survival (Cox proportional hazard modeling and Wald tests, P < .001). Among cervical cancer patients, TRL was associated with upregulated tumor G-CSF expression (χ(2) test, P < .001), elevated serum G-CSF levels (Student t test, P = .03), larger spleens (Student t test, P = .045), and increased MDSC frequencies in the blood (Student t test, P < .001) compared with the TRL-negative patients. In vitro and in vivo experiments revealed that tumor-derived G-CSF was involved in the underlying causative mechanism of TRL and MDSCs induced by tumor-derived G-CSF are responsible for the rapidly progressive and radioresistant nature of TRL-positive cervical cancer. The administration of anti-Gr-1 neutralizing antibody or the depletion of MDSCs by splenectomy (n = 6 per group) inhibited tumor growth and enhanced radiosensitivity in TRL-positive cervical cancer xenografts (Wilcoxon rank sum test, P = .008 and P = .02, respectively).
CONCLUSIONS: TRL is associated with resistance to radiotherapy among cervical cancer patients, and MDSC-targeting treatments may have therapeutic potential in these patients.

Lee MK, Jeong EM, Kim JH, et al.
Aberrant methylation of the VIM promoter in uterine cervical squamous cell carcinoma.
Oncology. 2014; 86(5-6):359-68 [PubMed] Related Publications
OBJECTIVES: To identify prognosis-associated methylation markers of uterine cervical squamous cell carcinoma (SCC) and to verify potential clinical correlations.
METHODS: A genome-wide methylation array was performed using tissue samples of stage Ib1 (n = 9) and IIa (n = 5) tumors. Methylation levels were quantitatively evaluated by pyrosequencing for 54 tissue samples from SCC patients and 22 samples from normal controls. Clinicopathologic findings were obtained from medical records. Correlation or t test statistics were used to analyze the relationships between methylation levels and clinical features. Survival data were estimated using the Kaplan-Meier method and compared to the log-rank test.
RESULTS: The methylation array identified 32 genes with distinct differences (p < 0.01) between stage Ib1 and IIa disease, and VIM was selected for further evaluation. Pyrosequencing analysis revealed that 40.7% of carcinoma samples had a higher methylation level in the VIM gene compared to the normal controls. VIM methylation status, low FIGO stage, and lack of parametrial involvement were significantly associated with longer disease-free survival (p = 0.036, p = 0.028, and p = 0.001, respectively).
CONCLUSIONS: We profiled 32 genes that might be associated with prognosis in cervical cancer. We further revealed that the VIM gene is frequently methylated in cervical SCC and that its methylation might predict a favorable prognosis.

Randolph ML, Wu HH, Crabtree WN
Reprocessing unsatisfactory ThinPrep papanicolaou tests using a modified SurePath preparation technique.
Cancer Cytopathol. 2014; 122(5):343-8 [PubMed] Related Publications
BACKGROUND: The frequency of unsatisfactory gynecologic specimens has increased in the study laboratory over the last few years due to the advent of personal lubricants. Similarly, lysed blood, protein, and necrotic debris present a challenge in terms of negative cell transference caused by a clogged filter. In the current study, the authors evaluated the potential use of a modified SurePath reprocessing technique to decrease the frequency of unsatisfactory specimens.
METHODS: An aliquot for human papillomavirus testing was set aside and the remaining specimen in the ThinPrep vial was submitted for sedimentation. A methanol wash was performed using preservative that was added to the remaining sediment. The specimen was vortexed and a protein wash of Tris-buffered deionized water was added before processing. The specimens were stained using the ThinPrep staining protocol. Both the original specimen and the reprocessed specimens were manually reviewed by 1 cytotechnologist and 2 pathologists to determine specimen adequacy.
RESULTS: A total of 1937 ThinPrep Papanicolaou tests were reprocessed and examined. Of these, 1093 (56%) specimens were satisfactory, 624 of which (57%) demonstrated evidence of a transformation zone component. Epithelial cell abnormalities were identified in 116 specimens (10.6%), including 11 high-grade squamous intraepithelial lesion specimens (1.0%); 5 specimens with a classification of atypical squamous cells, cannot rule out a high-grade lesion (0.5%); 21 low-grade squamous intraepithelial lesion specimens (1.9%); and 79 specimens classified as atypical squamous cells of undetermined significance (7.2%).
CONCLUSIONS: The modified SurePath processing technique was adept at handling nearly all of the challenges that biological and environmental conditions (blood, protein, lubricant, etc) present in liquid-based filter preparations. A total of 1093 (56%) of 1937 unsatisfactory ThinPrep Papanicolaou tests were converted to a satisfactory state, resulting in 116 abnormalities (10.6%) being diagnosed that otherwise would have gone undetected

Lin Y, Zhan FB
Geographic variations of racial/ethnic disparities in cervical cancer mortality in Texas.
South Med J. 2014; 107(5):281-8 [PubMed] Related Publications
OBJECTIVES: To examine how racial/ethnic disparities of cervical cancer mortality vary geographically and to identify factors contributing to the variation.
METHODS: Using the population-weighted risk difference, the authors investigated geographic patterns of racial/ethnic disparities in cervical cancer mortality in Texas based on data from 1995 to 2008 georeferenced at the census tract level. In addition, we considered the impact of seven factors--stage at diagnosis, spatial access to health care, and five factors that were created from available demographic data: socioeconomic status (SES), the sociodemographic factor, the percentage of African Americans, the health insurance factor, and the behavioral factor--on racial/ethnic disparities in the analysis using multivariate logistic regression.
RESULTS: SES, the sociodemographic factor, the percentage of African Americans, and racial/ethnic disparities in late-stage diagnosis in a census tract were independent predictors of a census tract's displaying significant racial/ethnic disparities in cervical cancer mortality. Compared with a census tract with the highest SES, a census tract with the lowest SES was more likely to have higher mortality rates in African Americans (odds ratio 4.19, confidence interval 2.18-8.07) or Hispanics (odds ratio 8.15, confidence interval 5.27-12.61) than non-Hispanic whites after adjusting for covariates. Health insurance expenditures also influenced racial/ethnic disparities in mortality, although this effect was attenuated after adjusting for covariates. Neither our calculated behavioral factor nor spatial analysis of access to health care explained racial/ethnic gaps in mortality.
CONCLUSIONS: Findings from this study could allow cervical cancer intervention programs to more clearly identify areas that would reduce disparities in cervical cancer outcomes.

Rahman T, Tabassum S, Jahan M, et al.
Detection and estimation of human papillomavirus viral load in patients with cervical lesions.
Bangladesh Med Res Counc Bull. 2013; 39(2):86-90 [PubMed] Related Publications
Human papillomavirus (HPV) high risk genotype infection and HPV viral load influences the development of invasive cervical cancer and cervical intra-epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may play a potential role in its early detection and management. The present study detected HPV DNA and estimated HPV viral load in different types of cervical lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases were positive for HPV DNA. The highest viral load (501 x 10(3) copies/ml) was detected in a patient with invasive carcinoma, while the lowest viral load (105 x 10(3) copies/ml) was detected from a case of chronic cervicitis. The mean viral load in CIN I was 119.25 x 10(3) +/- 12.5 x 10(3) copies/ml (range: 110 x 10(3) - 137 x 10(3) ) and 208.50 x 10(3) +/- 0.59 x 10(3) copies/ml (range: 139 x 10(3) - 305 x 10(3)) in CIN II/III. Interestingly, HPV DNA was detected from a patient with normal cytological findings. Our study observed a moderate presence of high-risk HPV genotypes among women with cervical lesions. The HPV viral load varied with the age of the patients and stage of cervical lesions. The HC2 assay is a promising tool for diagnosing high-risk HPV infection especially before cytology tests show any abnormality.

Einck JP, Hudson A, Shulman AC, et al.
Implementation of a high-dose-rate brachytherapy program for carcinoma of the cervix in Senegal: a pragmatic model for the developing world.
Int J Radiat Oncol Biol Phys. 2014; 89(3):462-7 [PubMed] Related Publications
West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single (60)Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

Related: Brachytherapy

Razmpoosh M, Sansregret A, Oligny LL, et al.
Assessment of correlation between p16INK4a staining, specific subtype of human papillomavirus, and progression of LSIL/CIN1 lesions: first comparative study.
Am J Clin Pathol. 2014; 142(1):104-10 [PubMed] Related Publications
OBJECTIVES: To study and compare the effectiveness of p16(INK4a) staining and specific human papillomavirus (HPV) subtypes as a prognostic marker in cervical intraepithelial neoplasia grade 1 (CIN1; low-grade squamous intraepithelial lesions).
METHODS: Sixty-four cervical samples diagnosed as CIN1 and stained with p16(INK4a), with HPV status assessed by polymerase chain reaction-direct sequencing.
RESULTS: Of the 34 p16(INK4a)-negative biopsy specimens, 26 regressed, seven persisted, and one progressed. Of the 20 p16(INK4a) diffusely positive biopsy specimens, seven regressed, eight persisted, and five progressed. Ten biopsy specimens stained positive only in the lower one-third of the sample, of which seven regressed and three persisted. p16(INK4a) diffusely positive CIN1 lesions were associated with only high-risk HPV subtypes, with the exception of one HPV-negative biopsy specimen. Three different high-risk HPV subtypes and one low-risk HPV subtype (HPV66) were identified in the six CIN1 lesions that progressed.
CONCLUSIONS: There is a significant relationship between p16(INK4a) immunostaining and follow-up (P = .002). p16(INK4a)-negative specimens or positivity in the lower one-third of CIN1 lesions seldom progress to a CIN2-3 lesion.

Wright TC, Stoler MH, Agreda PM, et al.
Clinical performance of the BD Onclarity HPV assay using an adjudicated cohort of BD SurePath liquid-based cytology specimens.
Am J Clin Pathol. 2014; 142(1):43-50 [PubMed] Related Publications
OBJECTIVES: To compare the performance of the BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) in BD SurePath liquid-based cytology media with that of Hybrid Capture 2 (HC2, Qiagen, Germantown, MD) samples co-collected in specimen transport medium in an adjudicated patient cohort.
METHODS: The performance of the BD Onclarity HPV Assay using BD SurePath media was compared with that of HC2 samples co-collected in specimen transport medium using 541 archived samples from a multicenter US clinical trial with histologically adjudicated cervical biopsy specimens.
RESULTS: The sensitivity for cervical intraepithelial neoplasia (CIN) 2 positivity (n - 104) was 90.4% (95% confidence interval [CI], 83-95) and 93.3% (95% CI, 87-97) and specificity was 76.9% (95% CI, 73-81) and 77.8% (95% CI, 74-82) for the BD assay and HC2, respectively. Nine cases of CIN 2+ had results discordant with the high-risk HPV assay. All were found to have been correctly classified with the BD assay using a novel WAVE denaturing high-performance liquid chromatography double-stranded DNA sequencing method.
CONCLUSIONS: The clinical performance of The BD Onclarity HPV Assay with respect to histology end points was similar to HC2. Moreover, discordant analysis revealed improved performance of the BD assay with respect to ability to provide extended genotyping information and lack of cross-reactivity with low-risk HPV types associated with cellular abnormalities. The relative risks for CIN 3 disease for HPV 31 and HPV 33/58 (combined) were comparable to that of HPV 18 in this population, suggesting that these genotypes may warrant monitoring in future studies.

Dobo C, Oshima CT, De Oliveira Lima F, et al.
Cell-cycle analysis and apoptosis-associated proteins in cervical lesions of Brazilian women.
Anticancer Res. 2014; 34(6):2789-96 [PubMed] Related Publications
AIM: The aim of the present study was to detect the relative expressions of p53, p21(Waf1/Cip1), p27(Kip1) Bcl-2 and cleaved caspase-3 in cervical lesion samples from Brazilian women by immunohistochemistry.
MATERIALS AND METHODS: A total of 230 cervical biopsies in paraffin-embedded blocks were studied: 43 were invasive squamous cell carcinomas (SCC), 52 carcinomas in situ/cervical intraepithelial neoplasias III (CIN III), 54 cervical intraepithelial neoplasias II (CIN II), 51 cervical intraepithelial neoplasias I (CIN I) and 30 non-neoplastic lesions (NN) with benign cellular changes.
RESULTS: Significant differences were observed in the p53 expression between the different groups: NN and CIN I (p=0.010); NN and CIN II (p<0.00001); CIN II and CIN III (p=0.02); CIN II and CIS (p=0.0220); CIN II and CEC (p=0.010). Regarding p21(WAF1/Cip1), significant differences were observed between NN and CEC (p=0.001); CIN I and CEC (p=0.001); CIN II and CIN III (p=0,001); CIN II and CIS (p=0.0004) and CIN II and CEC (p<0.0001). For p27(Kip1), significant differences were observed between NN and CIN I (p<0.00001); NN and CIN II (p<0.00001); NN and CIS (p=0.038); CIN I and CIN III (p=0.001); CIN I and CIS (p=0.009); CIN I and CEC (p=0.0001); CIN II and CIN III (p=0.0003); CIN II and CIS (p=0.002); CIN II and CEC (p< 0.00001). Bcl-2 and caspase-3 did not show remarkable differences between groups.
CONCLUSION: p53, p21(WAF1/CIP1), p27(KIP1) appear to be involved in the course of carcinogenesis. Rare expression of Bcl-2 and cleaved caspase-3 suggests that these proteins probably do not participate in cervical apoptosis.

Related: CDKN1A TP53

Crowley J, Morain CO, McGillicuddy E, Kennelly P
An example of ideal utilisation of specialist services by primary care: cervical check.
Ir Med J. 2014; 107(5):156-7 [PubMed] Related Publications
Cancer of the cervix is the 8th most common cancer for women in Ireland.Cervical Check has organised and combated this clinical presentation nationwide and has shown encouraging figures since its launch in 2007. While working in Kerry General Hospital (KGH), the Southwest Specialist Training Scheme in General Practice carried out an audit of the colposcopy referrals being received from GPs in the southwest. Adherence to Cervical Check referral guidelines was the main focus of the audit. Very positive figures presented in round one of the audit cycle, with 51 (90%) of all GP referrals adhering to the guidelines. This was further improved by a GP information campaign, leading to 57 (93%) of referrals meeting the appropriate referral criteria. Overall, this paper highlights the excellent screening programme that is Cervical Check and the superb working relationship between primary and secondary care facilities.

Loizzi V, Cormio G, Lobascio PL, et al.
Bowel dysfunction following nerve-sparing radical hysterectomy for cervical cancer: a prospective study.
Oncology. 2014; 86(4):239-43 [PubMed] Related Publications
OBJECTIVE: To objectively assess anorectal dysfunction following nerve-sparing radical hysterectomy in stage I-II cervical carcinoma patients.
MATERIAL AND METHODS: Between 2008 and 2012, 21 patients with primary cervical cancer stage FIGO I-II were enrolled in this prospective study. All women underwent nerve-sparing radical hysterectomy. Anorectal manometry was performed preoperatively and 6 months after surgery. A paired Student t test was used to assess the statistical difference between the manometric evaluations. A p value <0.05 was considered statistically significant.
RESULTS: Twenty-one patients were available for follow-up. Maximal and mean anal resting and squeezing pressures were unaffected by the surgical procedure, rectoanal inhibitory reflex and length of the high anal pressure zone did not change after the operation. The minimal volume to elicit rectal sensation, urge to defecate and maximal tolerable volume did not change significantly in the postoperative period, although they decreased in 2 and increased in 3 patients. In addition, rectal compliance did not change after surgery. Furthermore, no significant differences were found between patients who were or were not treated with adjuvant radiotherapy.
CONCLUSIONS: Our findings suggest that nerve-sparing radical hysterectomy for cervical cancer does not seem to be associated with long-term anorectal dysfunction. © 2014 S. Karger AG, Basel.

Nair JJ, Rárová L, Strnad M, et al.
Crinane alkaloids of the amaryllidaceae with cytotoxic effects in human cervical adenocarcinoma (HeLa) cells.
Nat Prod Commun. 2014; 9(4):461-6 [PubMed] Related Publications
The family Amaryllidaceae has a long history of usage in the traditional medicinal practices of the indigenous peoples of South Africa, with three of its species known to be used for cancer treatment. Furthermore, the Amaryllidaceae is widely recognized for its unique alkaloid constituents, several of which exhibit potent and selective cytotoxic activities. In this study, several crinane alkaloids derived from local Amaryllidaceae species were examined for cytotoxic effects against the human cervical adenocarcinoma cell line, of which distichamine was the most potent (IC50 2.2 microM).

Samaras AT, Murphy K, Nonzee NJ, et al.
Community-campus partnership in action: lessons learned from the DuPage County Patient Navigation Collaborative.
Prog Community Health Partnersh. 2014; 8(1):75-81 [PubMed] Related Publications
BACKGROUND: Using community-based participatory research (CBPR), the DuPage County Patient Navigation Collaborative (DPNC) developed an academic campus-community research partnership aimed at increasing access to care for underserved breast and cervical cancer patients within DuPage County, a collar county of Chicago. Given rapidly shifting demographics, targeting CBPR initiatives among underserved suburban communities is essential.
OBJECTIVES: To discuss the facilitating factors and lessons learned in forging the DPNC.
METHODS: A patient navigation collaborative was formed to guide medically underserved women through diagnostic resolution and if necessary, treatment, after an abnormal breast or cervical cancer screening.
LESSONS LEARNED: Facilitating factors included (1) fostering and maintaining collaborations within a suburban context, (2) a systems-based participatory research approach, (3) a truly equitable community-academic partnership, (4) funding adaptability, (5) culturally relevant navigation, and (6) emphasis on co-learning and capacity building.
CONCLUSIONS: By highlighting the strategies that contributed to DPNC success, we envision the DPNC to serve as a feasible model for future health interventions.

Related: Breast Cancer Cancer Screening and Early Detection

Corcoran J, Crowley M
Latinas' attitudes about cervical cancer prevention: a meta-synthesis.
J Cult Divers. 2014; 21(1):15-21 [PubMed] Related Publications
Latina women are almost twice as likely to die from cervical cancer as Caucasian women. In response to this disparity, qualitative study has been devoted to this topic. In order to generalize knowledge, insights gleaned through qualitative research methodology may be integrated through meta-synthesis, a methodology that has developed in nursing and related health sciences. The primary purpose of this meta-synthesis was to obtain information about Latinas' knowledge, attitudes, and perceptions regarding cervical cancer and its screening. After applying inclusion criteria, nine studies were located. Results were organized around four areas of inquiry that cross-cut primary studies: 1) Latina participants' knowledge of cervical cancer and its prevention; 2) barriers for regular cervical cancer screening; 3) facilitators that encouraged such screening; and 4) recommendations on how to provide screening for Latina women. Findings indicated that culturally appropriate education and improving accessibility to health care were the most important overall themes for future efforts to improve screening rates among Latinas in the United States.

Related: USA

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