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).

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.

Related: Cancer Screening and Early Detection


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.

Related: COX2 (PTGS2) MKI67 BIRC5


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.

Related: Endometrial (Uterus) Cancer Endometrial Cancer


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.

Related: Cisplatin Paclitaxel


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.

Related: AKT1 Signal Transduction MTOR


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.

Related: Brachytherapy


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.

Related: Cancer Screening and Early Detection


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.

Related: Cancer Screening and Early Detection


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.

Related: Cisplatin Oxaliplatin


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.


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.

Related: MicroRNAs microRNA mir-21


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.

Related: Breast Cancer Breast Cancer Screening USA


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.


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.


Dickson EL, Vogel RI, Luo X, Downs LS
Recent trends in type-specific HPV infection rates in the United States.
Epidemiol Infect. 2015; 143(5):1042-7 [PubMed] Related Publications
SUMMARY This study examined recent trends in type-specific HPV infection rates in women referred for HPV typing as part of cervical cancer screening in the United States. HPV analyses were performed from March 2004 to March 2011. Women were aged 21-65 years at testing. The 18 most prevalent HPV types were analysed. Type-specific HPV infection rates were estimated in 3-month blocks. Lowess smoothing was used to examine time trends in infection rates for each HPV type, both combined, and separated by age group (younger women 21-30 years, older women 31-64 years). A total of 220914 women were included in the final analysis. The number of HPV tests performed on the younger age group increased, with the number of HPV infections and multiple type HPV infections decreasing. When separated by HPV type-specific analysis, the majority of HPV infection rates decreased; however, HPV types 61 and 83 increased. When analysing the older age group, there was a marked increase of the number of HPV tests. Overall, the rates of any HPV infection, as well as multiple type infections, were lower compared to the younger age group. The change in type-specific HPV rates in the older age group was minimal, with many rates remaining the same. In this population of women, overall rates of HPV infection decreased, while the number of HPV tests increased. Younger women had a more marked decrease in HPV infection rates, while for older women type-specific HPV infection rates appear consistent.

Related: Cancer Screening and Early Detection USA


Roma AA, Diaz De Vivar A, Park KJ, et al.
Invasive endocervical adenocarcinoma: a new pattern-based classification system with important clinical significance.
Am J Surg Pathol. 2015; 39(5):667-72 [PubMed] Related Publications
A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma. Tumors with pattern C showed diffusely infiltrative glands with associated extensive desmoplastic response. In total, 352 cases (all FIGO stages) from 12 institutions were identified. Mean patient age was 45 years (range, 20 to 83 y). Forty-nine (13.9%) cases demonstrated lymph nodes (LNs) with metastatic endocervical carcinoma. Using this new system, 73 patients (20.7%) were identified with pattern A tumors (all stage I); none had LN metastases and/or recurrences. Ninety patients (25.6%) were identified with pattern B tumors (all stage I); only 4 (4.4%) had LN metastases; 1 had vaginal recurrence. The 189 (53.7%) remaining patients had pattern C tumors; 45 (23.8%) of them had LN metastases. This new classification system demonstrated 20.7% of patients (pattern A) with negative LNs, and patients with pattern A tumors can be spared of lymphadenectomy. Patients with pattern B tumors rarely presented with metastatic LNs, and sentinel LN examination could potentially identify these patients. Aggressive treatment is justified in patients with pattern C tumors.


Salehi-Vaziri M, Sadeghi F, Alamsi-Hashiani A, et al.
Merkel cell polyomavirus and human papillomavirus infections in cervical disease in Iranian women.
Arch Virol. 2015; 160(5):1181-7 [PubMed] Related Publications
Human papillomavirus (HPV) infection is a necessary cause of cervical neoplasia. Concomitant infection with other infectious agents has been demonstrated to be a cofactor for HPV-related cervical carcinogenesis. The present investigation aimed to determine the prevalence of HPV and Merkel cell polyomavirus (MCPyV) infections and to evaluate the role of MCPyV as a co-factor for HPV-related cervical carcinogenesis in Iranian women. From 2011 to 2013, a total of 112 cervical samples were examined. Forty-five samples (40.2 %) were positive for HPV. MCPyV was found in 37 samples (33 %). Both HPV and MCPyV were present in 14 samples (12.5 %). MCPyV was seen in 30 % of squamous cell carcinomas, 37.5 % of adenocarcinomas, and 16.7 % of undifferentiated carcinomas. The MCPyV large T antigen (LT-Ag) DNA load was determined as the viral copy number per cell. The median MCPyV LT-Ag copy number in positive women was 0.049 × 10(-3) per cell (range 0.0006 × 10(-3)-4.558 × 10(-3) copies per cell). In comparison with other types of cervical cancer, the MCPyV LT-Ag load was higher in adenocarcinomas (0.1024 × 10(-3) copies per cell). A logistic regression model adjusted to HPV positivity and age revealed no statistically significant association between MCPyV infection and cervical cancer (OR, 1.12; 95 % CI, 0.07-16.83). More studies should be conducted to clarify the role of MCPyV in cervical carcinogenesis.

Related: Merkel Cell Polyomavirus


Simon MA, Tom LS, Nonzee NJ, et al.
Evaluating a bilingual patient navigation program for uninsured women with abnormal screening tests for breast and cervical cancer: implications for future navigator research.
Am J Public Health. 2015; 105(5):e87-94 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
OBJECTIVES: The DuPage Patient Navigation Collaborative evaluated the Patient Navigation Research Program (PNRP) model for uninsured women receiving free breast or cervical cancer screening through the Illinois Breast and Cervical Cancer Program in DuPage County, Illinois.
METHODS: We used medical records review and patient surveys of 477 women to compare median follow-up times with external Illinois Breast and Cervical Cancer Program and Chicago PNRP benchmarks of performance. We examined the extent to which we mitigated community-defined timeliness risk factors for delayed follow-up, with a focus on Spanish-speaking participants.
RESULTS: Median follow-up time (29.0 days for breast and 56.5 days for cervical screening abnormalities) compared favorably to external benchmarks. Spanish-speaking patients had lower health literacy, lower patient activation, and more health care system distrust than did English-speaking patients, but despite the prevalence of timeliness risk factors, we observed no differences in likelihood of delayed (> 60 days) follow-up by language.
CONCLUSIONS: Our successful replication and scaling of the PNRP navigation model to DuPage County illustrates a promising approach for future navigator research.

Related: Breast Cancer


Jang H, Baek JG, Jo S
The anal canal as a risk organ in cervical cancer patients with hemorrhoids undergoing whole pelvic radiotherapy.
Tumori. 2015 Jan-Feb; 101(1):72-7 [PubMed] Related Publications
AIMS AND BACKGROUND: Tolerance of the anal canal tends to be ignored in patients with cervical cancer undergoing whole pelvic radiotherapy. However, patients with hemorrhoids may be troubled with low radiation dose. We tried to analyze the dose-volume statistics of the anal canal in patients undergoing whole pelvic radiotherapy.
METHODS: The records of 31 patients with cervical cancer who received definite or postoperative radiotherapy at one institution were reviewed. Acute anal symptoms, such as anal pain and bleeding, were evaluated from radiotherapy start to 1 month after radiotherapy completion. Various clinical and dosimetric factors were analyzed to characterize relations with acute anal complications.
RESULTS: The anal verge was located an average of 1.2 cm (range -0.6~3.9) below the lower border of the ischial tuberosity and an average of 2.7 cm (range -0.6~5.7) behind the sacral promontory level. The presence of hemorrhoids before radiotherapy was found to be significantly associated with acute radiation-induced anal symptoms (p = 0.001), and the mean induction dose for anal symptoms was 36.9 Gy. No patient without hemorrhoids developed an anal symptom during radiotherapy. Dosimetric analyses of V30 and V40 showed marginal correlations with anal symptoms (p = 0.07).
CONCLUSIONS: The present study suggests a relation between acute anal symptoms following radiotherapy and acute hemorrhoid aggravation. Furthermore, the location of the anal verge was found to be variable, and consequently doses administered to the anal canal also varied substantially. Our results caution careful radiation treatment planning for whole pelvic radiotherapy, and that proper clinical management be afforded patients with hemorrhoids during radiotherapy.


Wang HY, Park S, Kim S, et al.
Use of hTERT and HPV E6/E7 mRNA RT-qPCR TaqMan assays in combination for diagnosing high-grade cervical lesions and malignant tumors.
Am J Clin Pathol. 2015; 143(3):344-51 [PubMed] Related Publications
OBJECTIVES: Human papillomavirus (HPV) is a major cause of cervical cancer, which is the second most common cancer in women. HPV E6 initiates degradation of cellular tumor suppressor protein p53, induces human telomerase reverse transcriptase (hTERT) activity, and then leads to progressive cervical carcinogenesis.
METHODS: In this study, the CervicGen HPV RT-qDX assay (Optipharm, Osong, Republic of Korea), which detects 16 HPV high-risk subtypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, and 69), and the CervicGen hTERT RT-qDX assay (Optipharm) were evaluated using 545 ThinPrep (Hologic, Bedford, MA) Papanicolaou samples.
RESULTS: The positivity for the HPV E6/E7 messenger RNA (mRNA) assay was 94.4%, 95.2%, 82.4%, 46.5%, 25.0%, and 1.1% in squamous cell carcinomas, high-grade squamous intraepithelial lesions (HSILs), atypical squamous cells--cannot exclude HSIL, low-grade squamous intraepithelial lesions, atypical squamous cells of undetermined significance, and normal cytology samples, respectively. Five cervical intraepithelial neoplasia grade 2+ samples were not detected by the HPV E6/E7 mRNA assay, but they exhibited positive signals in the hTERT mRNA assay. Notably, the hTERT mRNA expression level was increased in high-grade cervical lesions but was very low in all 288 normal samples.
CONCLUSIONS: These data suggest that the combination of HPV E6/E7 and hTERT mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions and malignant tumors and might be useful as a predictive marker in monitoring low-grade cervical lesions.

Related: TERT


Joura EA, Giuliano AR, Iversen OE, et al.
A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.
N Engl J Med. 2015; 372(8):711-23 [PubMed] Related Publications
BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.
METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.
RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.
CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).


Meyerson BE, Sayegh MA, Davis A, et al.
Cervical cancer screening in a sexually transmitted disease clinic: screening adoption experiences from a midwestern clinic.
Am J Public Health. 2015; 105 Suppl 2:e8-14 [PubMed] Related Publications
OBJECTIVES: We examined whether a sexually transmitted disease (STD) clinic could reach women who had not received a Papanicolau (Pap) test in the past 3 years. We also explored staff attitudes and implementation of cervical cancer screening.
METHODS: Women (n = 123) aged 30 to 50 years were offered cervical cancer screening in an Indiana STD clinic. We measured effectiveness by the patients' self-reported last Pap test. We explored adoption of screening through focus groups with 34 staff members by documenting their attitudes about cervical cancer screening and screening strategy adaptation. We also documented recruitment and screening implementation.
RESULTS: Almost half (47.9%) of participants reported a last Pap test 3 or more years previously; 30% had reported a last Pap more than 5 years ago, and 11.4% had a high-risk test outcome that required referral to colposcopy. Staff supported screening because of mission alignment and perceived patient benefit. Screening adaptations included eligibility, results provision, and follow-up.
CONCLUSIONS: Cervical cancer screening was possible and potentially beneficial in STD clinics. Future effectiveness-implementation studies should expand to include all female patients, and should examine the degree to which adaptation of selected adoption frameworks is feasible.

Related: Cancer Screening and Early Detection


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