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).

Thabet M, Hemida R, Hasan M, et al.
Human papillomavirus (HPV) is not the main cause of preinvasive and invasive cervical cancer among patients in Delta Region, Egypt.
J Exp Ther Oncol. 2014; 10(4):247-53 [PubMed] Related Publications
BACKGROUND: Cervical cancer remains a significant problem worldwide particularly in underdeveloped countries. It is necessary to have a persistent infection of the cervix with a high-risk or oncogenic human Papillomavirus (HPV) virus to develop cervical cancer.
OBJECTIVES: To study the association between HPV and pre-invasive and invasive cancer cervix among patients referred to Early Cancer Detection Clinic of Obstetrics and Gynecology Department, Mansoura University Hospital, Delta region, Egypt.
METHODS: Cervical specimens of 100 histologically confirmed premalignant and malignant cervical lesions were subjected to HPV detection and genotyping by extraction of DNA from cervical biopsy using a commercial PCR kit.
RESULTS: HPV DNA testing was done, 36 cases were positive (36%). Correlations of age, duration of marriage, and parity were non significant (P = 0.56, 0.72, and 0.35 respectively) while correlations of residence, oral contraceptive use, smoking, and immunosuppresion were sig- nificant (P = 0.006, 0.001, 0.001, and 0.01 respectively). The prevalence of HPV in premalignant and malignant cervical lesions in our study was 39.5% & 33.3% respec tively. The commonest HPV genotypes associated with premalignant cervical lesions were HPV16; 11/17(64.7%) and HPV18; 11/17 (64.7%) mostly in the form of mul- tiple infections with HPV16+18; 7/17 (41.17%). The commonest HPV genotypes associated with malignant cervical lesions in our cases were HPV16; 15/19 (78.9%) and HPV18; 13/19 (68.42%) also in the form of multiple infections with HPV16+18; 10/19 (52.63%).
CONCLUSION: The prevalence of HPV in premalignant and malignant cervical lesions was 39.5% & 33.3% respectively, this means that HPV is not the main cause of premalignant and malignant cervical lesions in Delta region in Egypt. HPV infection mostly in the form of multiple infections with HPV16+18 genotypes. Further studies are needed to clarify actual association of HPV and premalignant and malignant cervical lesions to determine the usefulness of HPV vaccination in our locality.

Ezeanochie MC, Olagbuji BN
Human papilloma virus vaccine: determinants of acceptability by mothers for adolescents in Nigeria.
Afr J Reprod Health. 2014; 18(3):154-8 [PubMed] Related Publications
Vaccination of adolescent females against Human Papilloma Virus (HPV), the causative agent for cervical cancer has recently become available. As minors, parental acceptance of the vaccines for adolescent daughters requires exploration. This was a cross-sectional survey of 201 mothers attending the gynaecology clinic in a University Teaching Hospital in Nigeria on acceptability of the HPV vaccines and its determinants. Although 70% accepted vaccination of their daughters, 30% were unwilling and the commonest reason for unwillingness was that it may encourage sexual promiscuity (62.3%). Mothers with poor knowledge of STI were significantly more unwilling to accept HPV vaccines compared to those with average or good knowledge (p = 0.002). Furthermore, perception of susceptibility to HPV infection by daughters was significantly associated with acceptance of the vaccines (p = 0.0001). Increased advocacy and public enlightenment on cervical cancer control and the role of HPV vaccines in its prevention is still necessary especially in developing countries.

Yang SW, Kim WY, Cho SH, et al.
Multifocal microinvasive squamous cell carcinoma with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, vagina, and left salpinx diagnosed five years after conization of cervical CIS.
Eur J Gynaecol Oncol. 2014; 35(5):600-3 [PubMed] Related Publications
BACKGROUND: Multifocal microinvasive squamous cell carcinoma (SCC) with extensive spread of squamous cell carcinoma in situ (CIS) into the uterine corpus, salpinx, and vagina is extremely unusual.
CASE: The authors present a case of 69-year-old woman with hydrometra who was found to have multifocal microinvasive SCC in the endometrium. The CIS had spread superficially throughout the entire endometrium up to the fundus, completely replacing the epithelium. The uterine cervix, vaginal surface and left salpingeal mucosa were involved. She had previously undergone conization due to cervical CIS five years prior. The pathologic reports showed clear resection margins at that time.
CONCLUSION: The present case suggests that CIS in the endometrium spread back to the cervix and vagina, although the definite origin of the first CIS was not determined.

Xiaolei C, Taot H, Zongli S, Hongying Y
The role of ureaplasma urealyticum infection in cervical intraepithelial neoplasia and cervical cancer.
Eur J Gynaecol Oncol. 2014; 35(5):571-5 [PubMed] Related Publications
AIM: To investigate the role of ureaplasma urealyticum (UU) infection in cervical intraepithelial neoplasia (CIN) and cervical cancer and to study the correlation between UU and HPV infection in CIN/cervical cancer.
MATERIALS AND METHODS: A total of 233 research subjects were divided into the case group and the control group. UU and pathogenic load UU were detected in the case group and the control group by fluorescence quantitative polymerase chain reaction (PCR) method, human papillomavirus (HPV) in case group by PCR + membrane hybridization method.
RESULTS: There was statistically significant difference in the case group and control group with respect to the positive rate and pathogenic load of UU (p < 0.05). The positive rate of UU among CIN II group, CIN III group, and the cervical cancer group were not statistically significant difference (p > 0.05). There may be statistically significant difference in the result of testing UU coinfection with HPV (p = 0.002).
CONCLUSION: Positive rate and the pathogenic load of UU infection may be related to the genesis of cervical cancer. Significant combined effect could strengthen the process of the disease and lead to the pathogenesis of cervical cancer between infection of HPV and UU.

Demirkiran F, Bese T, Meseci E, et al.
The surgical outcomes of abdominal radical trachelectomy: does transrectal ultrasonography determine the cervical incision site during surgery?
Eur J Gynaecol Oncol. 2014; 35(5):566-70 [PubMed] Related Publications
PURPOSE: To evaluate the surgical outcomes of abdominal radical trachelectomy(ART) and the efficacy of transrectal ultrasonography in determining the upper end of cervical incision during this operation.
MATERIALS AND METHODS: ART was performed in five patients with early-stage cervical cancer in the present clinic. In the first three patients, uterine corpus was transacted blindly at a level of approximately five mm below the internal os. In the last two patients, the authors performed transrectal ultrasonography before vaginal incision to evaluate the distance between upper margin of tumoral mass and internal os of cervical canal.
RESULTS: Mean follow-up was 21 months. During this period, menstrual abnormality occurred in three patients. The two patients in which transrectal ultrasonographies were taken intraoperatively had 9- and 12-mm postoperative cervical canal length and both of them were asymptomatic postoperatively.
CONCLUSIONS: ART is usually associated with menstrual abnormality at late postoperative period and transrectal ultrasonograph during this procedure may decrease postoperative morbidity.

Li C, Ma C, Zhang W, Wang J
The immune function differences and high-risk human papillomavirus infection in the progress of cervical cancer.
Eur J Gynaecol Oncol. 2014; 35(5):557-61 [PubMed] Related Publications
INVESTIGATION: To study the differences immune function in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical cancer tissue, and study the relationship between human papillomavirus (HPV) infection and cervical local immune function.
MATERIALS AND METHODS: This study determined the form, quantity, distribution, and intensity of CD4+Th cells, S-100+ dendritic cells (DCs) and CD57+NK cells in the normal cervical tissue, CIN cervical tissue, and cervical cancer by histopathological and image analyses.
RESULTS: The immune function was differences in the progress of cancer genesis. The numbers of the CD4+ Th cells, S-100+ DCs, and CD57+NK cells increased with the progress of the disease in CIN, but when cancer occurred, immune cells decreased in local cervical tissue.
CONCLUSION: From lesion precancerous to infiltrating carcinoma, the form, quantity, and intensity of expression of immune cells changed, which may indicate that the cervical local immune function has changed. Furthermore, high-risk HPV infections are more active in local immune function.

Coşar E, Gencer M, Hacivelioğlu SO, et al.
HPV and HPV vaccination: knowledge and consciousness of young women.
Eur J Gynaecol Oncol. 2014; 35(5):554-6 [PubMed] Related Publications
AIM: The aim of the study was to explore the knowledge and the awareness of the young Turkish women regarding cervical cancer and human papilloma virus (HPV) vaccines. The authors analyze a probable relationship between the overall knowledge level and a few socio-demographic parameters.
MATERIALS AND METHODS: The authors interviewed with students from Canakkale 18 March University and young women that did not continue with school in the same city from January to September 2011. All the students answered the questionnaire voluntarily and independently.
RESULTS: The participants had low level of knowledge about the risk factors for cervical cancer. Smoking is the major risk factor that was known by the participants (65%). Proportion of the participants that were aware of pap smear test and HPV were 65% and 17% respectively. A small proportion of young women had knowledge regarding protection from HPV. Educational stream, educational level, family income, and family size had significant association knowledge level (p < 0.05).
CONCLUSION: There has not been any improvement in HPV and risk factor of cervical cancer awareness in young women. Health members of the National Cancer Control Programme and delegates of the vaccine corporations have major work in order to increase the level of knowledge so that general public can easily take preventative measures.

Cossu A, Capobianco G, Budroni M, et al.
Report on incidence and mortality trends of cervical cancer in northern Sardinia, Italy.
Eur J Gynaecol Oncol. 2014; 35(5):544-7 [PubMed] Related Publications
INTRODUCTION: The aim of this study was to analyze and describe the incidence and mortality trends of cervical cancer in northern Sardinia, Italy, in the period 1992-2010.
MATERIALS AND METHODS: Data were obtained from the tumor registry of Sassari province which is part of a wider registry web, coordinated today by the Italian Association for Tumor Registries.
RESULTS: The overall number of cervical cancer cases registered in the period under investigation was 311. The mean age of the patients was 51.8 years. The standardized incidence and mortality rates were 6.6 / 100.000 and 0.7 / 100.000, respectively. A stable trend in incidence and mortality of cervical cancer was evidenced. Relative survival at five years from diagnosis was fairly good (66.3%).
CONCLUSIONS: The incidence and mortality trends of cervical cancer in northern Sardinia remained relatively stable in the last decades. Furthermore, survival of patients with cervical cancer is good in the area, sanctioning the adequacy of the preventive and clinical measures in use.

Yamashita H, Niibe Y, Okuma K, et al.
Treatment results for Stage Ib cervical cancer after stage subdivision by MRI evaluation.
Eur J Gynaecol Oncol. 2014; 35(5):499-502 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: The authors analyzed treatment results for cervical cancer after subdividing Stage Ib into Stages Ib1 and Ib2 according to magnetic resonance imaging (MRI) information.
MATERIALS AND METHODS: The subjects comprised 40 cases of Stage Ib cervical cancer treated by definitive radiotherapy in Kitasato University hospital and Tokyo University hospital from January 2000 to December 2008. The patients' ages ranged from 28 to 85 years (median: 68 years). The maximum tumor diameter measured with MRI ranged from undetectable to 60 mm (median: 25 mm). The authors classified tumors with the greatest dimension less than 40 mm as Stage Ib1 (29 cases) and those with the greatest dimension more than 40 mm as Ib2 (11 cases). All cases were treated with a combination of external beam irradiation and high-dose-rate intra-cavitary brachytherapy. Chemotherapy was combined with radiotherapy in 11 cases.
RESULTS: The follow-up time was from four to 109 months (median: 53 months). At the time of last observation, 37 cases survived, local recurrence was seen in none, and two cases showed distant metastasis. The two- and five-year overall survival rates of all cases were 97.5% and 89.5%, respectively. When a stage was subdivided and examined, the five-year overall survival rate of Stage Ib1 was 100% and that of Stage Ib2 was 50.5% (p = 0.001).
CONCLUSION: The authors suggest that the subdivision of stages using image information reflects the prognosis of Stage Ib cervical cancer.

Reuschenbach M, Wentzensen N, Dijkstra MG, et al.
p16INK4a immunohistochemistry in cervical biopsy specimens: A systematic review and meta-analysis of the interobserver agreement.
Am J Clin Pathol. 2014; 142(6):767-72 [PubMed] Related Publications
OBJECTIVES: The interpretation of cervical biopsy specimens guides management of women with suspected cervical cancer precursors. However, morphologic evaluation is subjective and has low interobserver agreement. Addition of p16(INK4a) immunohistochemistry may improve interpretation.
METHODS: We performed a systematic review and meta-analysis of published data on interobserver agreement of p16(INK4a) positivity using p16(INK4a) immunohistochemistry and of cervical intraepithelial neoplasia grade 2 (CIN2+) and CIN grade 3 (CIN3+) classification using H&E morphology in conjunction with p16(INK4a) in comparison with H&E morphology alone.
RESULTS: The literature search revealed five eligible articles. The results show strong agreement of pathologists' interpretation of cervical biopsy specimens as p16(INK4a) positive or negative (pooled κ = 0.90; 95% confidence interval [CI], 0.88-0.92) and significantly higher agreement for a CIN2+ diagnosis with H&E morphology in conjunction with p16(INK4a) (κ = 0.73; 95% CI, 0.67-0.79) compared with H&E morphology alone (κ = 0.41; 95% CI, 0.17-0.65). Also, a slightly higher agreement for CIN3+ can be observed (κ = 0.66; 95% CI, 0.39-0.94 for H&E morphology in conjunction with p16(INK4a) and κ = 0.61; 95% CI, 0.44-0.78 for H&E morphology alone), but this difference was not statistically significant.
CONCLUSIONS: The published literature indicates improved interobserver agreement of the diagnosis of CIN2+ with the conjunctive use of H&E morphology with p16(INK4a) immunohistochemistry compared with H&E morphology alone.

Benard VB, Thomas CC, King J, et al.
Vital signs: cervical cancer incidence, mortality, and screening - United States, 2007-2012.
MMWR Morb Mortal Wkly Rep. 2014; 63(44):1004-9 [PubMed] Related Publications
BACKGROUND: Cervical cancer screening is one of the greatest cancer prevention achievements, yet some women still develop or die from this disease.
OBJECTIVE: To assess recent trends in cervical cancer incidence and mortality, current screening percentages, and factors associated with higher incidence and death rates and inadequate screening.
METHODS: Percentages of women who had not been screened for cervical cancer in the past 5 years were estimated using data from the 2012 Behavioral Risk Factor Surveillance System survey. State-specific cervical cancer incidence data from the United States Cancer Statistics and mortality data from the National Vital Statistics System were used to calculate incidence and death rates for 2011 by state. Incidence and death rates and annual percentage changes from 2007 to 2011 were calculated by state and U.S. Census region.
RESULTS: In 2012, the percentage of women who had not been screened for cervical cancer in the past 5 years was estimated to be 11.4%; the percentage was larger for women without health insurance (23.1%) and for those without a regular health care provider (25.5%). From 2007 to 2011, the cervical cancer incidence rate decreased by 1.9% per year while the death rate remained stable. The South had the highest incidence rate (8.5 per 100,000), death rate (2.7 per 100,000), and percentage of women who had not been screened in the past 5 years (12.3%).
CONCLUSIONS: Trends in cervical cancer incidence rates have decreased slightly while death rates have been stable over the last 5 years. The proportion of inadequately screened women is higher among older women, Asians/Pacific Islanders, and American Indians/Alaska Natives.
IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: There continue to be women who are not screened as recommended, and women who die from this preventable cancer. Evidence-based public health approaches are available to increase women's access to screening and timely follow-up of abnormal results.

Related: USA

Branch BC, Henry J, Vecil GG
Brain metastases from cervical cancer--a short review.
Tumori. 2014 Sep-Oct; 100(5):e171-9 [PubMed] Related Publications
AIMS AND BACKGROUND: Brain metastases from cervical cancer are extremely rare yet local recurrence and systemic spread is fairly common. The role of surgical resection and CNS screening for this pathology was interrogated from a review of the literature.
CLINICAL EXPERIENCE: We present a case of a single brain metastasis that originated from the cervix and describe chronologically the spread of the disease with pathological confirmations.
REVIEW: Following an extensive English literature search, which only yielded 59 reported cases (n = 60 including the present case), we extrapolated basic trends regarding the demographics, pathophysiology, and treatment that portended a longer survival. Despite treatment, the majority of patients do not survive past 1 year from diagnosis of intracranial metastasis. A trend towards prolonged survival was observed among patients who received surgical resection of the brain metastasis.
CONCLUSIONS: Cervical carcinoma has been documented to metastasize to the brain, and this may occur via initial seeding of the lungs. Surgical resection and CNS screening may have beneficial roles in the management of metastatic cervical carcinoma.

Langerak T, Heijkoop S, Quint S, et al.
Towards automatic plan selection for radiotherapy of cervical cancer by fast automatic segmentation of cone beam CT scans.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 1):528-35 [PubMed] Related Publications
We propose a method to automatically select a treatment plan for radiotherapy of cervical cancer using a Plan-of-the-Day procedure, in which multiple treatment plans are constructed prior to treatment. The method comprises a multi-atlas based segmentation algorithm that uses the selected treatment plan to choose between two atlas sets. This segmentation only requires two registration procedures and can therefore be used in clinical practice without using excessive computation time. Our method is validated on a dataset of 224 treatment fractions for 10 patients. In 37 cases (16%), no recommendation was made by the algorithm due to poor image quality or registration results. In 93% of the remaining cases a correct recommendation for a treatment plan was given.

Lewinska A, Adamczyk J, Pajak J, et al.
Curcumin-mediated decrease in the expression of nucleolar organizer regions in cervical cancer (HeLa) cells.
Mutat Res Genet Toxicol Environ Mutagen. 2014; 771:43-52 [PubMed] Related Publications
Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans.

Viswanathan AN, Erickson B, Gaffney DK, et al.
Comparison and consensus guidelines for delineation of clinical target volume for CT- and MR-based brachytherapy in locally advanced cervical cancer.
Int J Radiat Oncol Biol Phys. 2014; 90(2):320-8 [PubMed] Article available free on PMC after 01/10/2015 Related Publications
OBJECTIVE: To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy.
METHODS AND MATERIALS: Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case.
RESULTS: For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR.
CONCLUSION: In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx.

Related: Brachytherapy

Liu R, Wang X, Tian JH, et al.
High dose rate versus low dose rate intracavity brachytherapy for locally advanced uterine cervix cancer.
Cochrane Database Syst Rev. 2014; 10:CD007563 [PubMed] Related Publications
BACKGROUND: This is an updated version of the original Cochrane review published in 2010 (Issue 7).Carcinoma of the uterine cervix is the second most common cancer and the third leading cause of cancer death among women. Radiotherapy has been used successfully to treat cervical cancer for nearly a century. The combination of external beam radiotherapy (EBRT) and intracavity brachytherapy (ICBT) has become a standard treatment for cervical cancer. Whether high dose rate (HDR) or low dose rate (LDR) brachytherapy improves outcomes in terms of local control rates, survival and complications for women with cervical cancer remains controversial.
OBJECTIVES: To assess the efficacy and safety of HDR versus LDR ICBT in combination with EBRT for women with uterine cervical cancer.
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (1966 to March 2014), EMBASE (1974 to March 2014), and the Chinese Biomedical Literature Database (CBM) (1978 to March 2014) for relevant original, published trials.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that compared HDR with LDR ICBT, combined with EBRT, for women with locally advanced uterine cervical cancer.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data using standardised forms. Primary outcome measures included overall survival (OS), relapse-free survival (RFS) and pelvic control rate, while secondary outcomes included rates of recurrence and complications.
MAIN RESULTS: Four studies involving 1265 women met the inclusion criteria. In our meta-analysis to compare HDR and LDR ICBT, the pooled risk ratios (RRs) were 0.95 (95% confidence interval (CI) 0.79 to 1.15), 0.93 (95% CI 0.84 to 1.04) and 0.79 (95% CI 0.52 to 1.20) for 3-, 5- and 10-year overall survival rates respectively; and 0.95 (95% CI 0.84 to 1.07) and 1.02 (0.88 to 1.19) for 5- and 10-year disease-specific survival (DSS) rates respectively. The RR for RFS was 1.04 (95% CI 0.71 to 1.52) and 0.96 (95% CI 0.81 to 1.14) at 3- and 5- years. For local control rates the RR was 0.95 (95% CI 0.86 to 1.05) and 0.95 (95% CI 0.87 to 1.05) at 3- and 5- years; with a RR of 1.09 (95% CI 0.83 to 1.43) for locoregional recurrence, 0.79 (95% CI 0.40 to 1.53) for local and distant recurrence, 2.23 (95% CI 0.78 to 6.34) for para-aortic lymph node metastasis, and 0.99 (95% CI 0.72 to 1.35) for distance metastasis. For bladder, rectosigmoid and small bowel complications, the RR was 1.33 (95% CI 0.53 to 3.34), 1.00 (95% CI 0.52 to 1.91) and 3.37 (95% CI 1.06 to 10.72) respectively. These results indicated that there were no significant differences except for increased small bowel complications with HDRs (P = 0.04).
AUTHORS' CONCLUSIONS: Since the last version of this review, no new studies were identified for inclusion in this review to provide additional information. This review showed no significant differences between HDR and LDR ICBT when considering OS, DSS, RFS, local control rate, recurrence, metastasis and treatment related complications for women with cervical carcinoma. Due to some potential advantages of HDR ICBT (rigid immobilization, outpatient treatment, patient convenience, accuracy of source and applicator positioning, individualized treatment) we recommend the use of HDR ICBT for all clinical stages of cervix cancer. The overall risk of bias was high for the included studies as many of the items were either of high or unclear risk. The GRADE assessment of the quality of the evidence was low to moderate.

Related: Brachytherapy

Logan M, Hawkins SM
Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies.
Clin Sci (Lond). 2015; 128(3):153-80 [PubMed] Related Publications
microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using in vitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract.

Related: Endometrial (Uterus) Cancer Endometrial Cancer MicroRNAs Ovarian Cancer

Abid N, Mnif H, Mellouli M, et al.
Uterine tumour resembling ovarian sex cord tumours presenting as multiple endometrial and cervical uterine polyps: a case report.
Pathologica. 2014; 106(2):73-6 [PubMed] Related Publications
BACKGROUND: Uterine tumours resembling ovarian sex-cord tumours (UTROSCT) are very rare, benign uterine tumours, composed solely of sex cord elements. These tumours have a polyphenotypic immunophentype that favours a derivation from uterine mesenchymal stem cells.
CASE REPORT: A 43-year-old female presented with recurrent vaginal bleeding. On hysteroscopy, she had multiple endometrial and cervical polyps that were removed endoscopically. Histologically, the specimen contained epithelioid cells arranged in tubules, trabeculae and anastomosing cords, without significant cellular atypia or mitotic activity. Immunohistochemical studies were performed. The tumour was found to be diffusely positive for vimentin, calretinin and desmin, focally positive for cytokeratin, CD99 and inhibin and negative for chromogranin and CD10. A subsequent total hysterectomy was performed and revealed neoplastic infiltration of the myometrium.
CONCLUSION: A polyphenotypic immunophenotype is a characteristic feature of UTROSCT, and may be helpful in diagnosis and in exclusion of other lesions. Familiarity with this tumour by gynaecologists and pathologists is essential to avoid misdiagnosis:correct diagnosis of this neoplasm is important in patient management.

Related: Endometrial (Uterus) Cancer Endometrial Cancer Ovarian Cancer

Bogani G, Cromi A, Serati M, et al.
A prospective case-control study on the impact of neoadjuvant chemotherapy on surgery-related outcomes of laparoscopic radical hysterectomy.
Anticancer Res. 2014; 34(10):5703-8 [PubMed] Related Publications
AIM: To investigate whether perioperative outcomes of class III/type C laparoscopic radical hysterectomy (LRH) for cervical cancer (CC) are influenced by neoadjuvant chemotherapy (NACT).
PATIENTS AND METHODS: Data of consecutive patients, affected by locally advanced-stage CC, undergoing NACT plus LRH were matched 1:2 with consecutive patients, affected by early-stage CC who underwent LRH without NACT.
RESULTS: Twenty and 40 patients underwent NACT with LRH and LRH aIone, respectively. Demographic characteristics were balanced between groups. Number of lymph nodes yielded, parametrial width and length of vaginal cuff were not influenced by preoperative administration of NACT. Patients undergoing NACT plus LRH experienced slightly higher blood loss (225 vs. 200 ml; p=0.05) than patients in the control group, but had a similar operative time and length of hospital stay. No between-group differences in transfusion and complications rates were observed (p>0.2).
CONCLUSION: The administration of NACT does not affect the surgery-related outcomes of LRH.

Gokhale P, Mania-Pramanik J, Sonawani A, et al.
Cervical cancer in Indian women reveals contrasting association among common sub-family of HLA class I alleles.
Immunogenetics. 2014; 66(12):683-91 [PubMed] Related Publications
We studied the relationship between human leukocyte antigen (HLA) class I alleles and cervical cancer among Indian women. Seventy-five cervical cancer cases were compared with 175 noncancer controls. Cervical biopsy tissue specimen from cancer cases and cervical swab specimen from controls were collected for HPV detection and typing. Blood was taken for HLA typing by PCR-SSOP method. The impact of HLA class I alleles on cervical cancer risk was evaluated using StatCalc program (Epi Info version 6.0.4. CDC Atlanta, GA, USA), and confirmed with Bonferroni correction. Results revealed HLA-B*37, HLA-B*58 were associated significantly with increased risk while HLA-B*40 with decreased risk for cervical cancer. At high-resolution analysis after Bonferroni correction, HLA-B*37:01 allele was associated with increased risk, whereas HLA-B*40:06 was with decreased risk for cervical cancer. HLA-B*37:01 and HLA-B*40:06 belong to the same superfamily of HLA-B44. In silico analysis revealed different binding affinities of HLA-B*37:01 and HLA-B*40:06 for the epitopes predicted for E6 and L1 proteins of HPV16. The higher binding affinity of epitopes to B*40:06, as revealed by docking studies, supports the hypothesis that this allele is able to present the antigenic peptides more efficiently than B*37:01 and thereby can protect the carriers from the risk of cervical cancer. Thus, there is a clear indication that HLA plays an important role in the development of cervical cancer in HPV-infected women. Identification of these factors in high-risk HPV-infected women may help in reducing the cervical cancer burden in India.

Kolnikova G, Ondrusova M, Repiska V, et al.
Current possibilities of cervical precancerous lesions screening in Slovakia: prevalence of high risk human papillomavirus in patients with cytological diagnoses of atypical squamous cells of unknown significance.
Bratisl Lek Listy. 2014; 115(8):469-73 [PubMed] Related Publications
INTRODUCTION: It has been confirmed, that there is a causal relationship between persistent infection of high risk human papillomavirus (HR-HPV) and the development of cervical cancer. In population of women older than 30 years HPV infection becomes a significant etiological factor of precancerous lesion of the cervix, but HPV infection may spontaneously regress in the majority of the cases.
PATIENTS AND METHODS: The analysed study group consisted of 397 samples with cytological diagnosis of atypical squamous cells of unknown significance (ASCUS). All cases underwent HPV DNA testing using the Hybrid Capture 2 (HC2) assay. We analysed prevalence of HR-HPV and a viral load expressed as relative light units/cut off ratio (RLU/CO) in different age groups with cytological diagnoses of ASCUS.
RESULTS: The prevalence of HR-HPV with cytological diagnoses of ASCUS was detected in 44 %. The prevalence of HR-HPV between patients aged 17-29 and between patients aged 30-40 was 55 % and 48 % respectively and we detected significant reduction of prevalence (28 %) in patients older than 41 years.
CONCLUSION: Based on the results of presented study we assumed that age the 40 and over is crucial for the development of serious precancerous lesions in Slovakia, thus this age group is the most suitable for HPV triage of ASCUS. As a refinement of that type of ASCUS triage we recommend to add to the algorithm quantitative measurement of viral load in the specimens in the form of RLU/CO ratio (Fig. 3, Ref. 27).

Brown DS, Poulos C, Johnson FR, et al.
Adolescent girls' preferences for HPV vaccines: a discrete choice experiment.
Adv Health Econ Health Serv Res. 2014; 24:93-121 [PubMed] Related Publications
PURPOSE: To measure adolescent girls' preferences over features of human papillomavirus (HPV) vaccines in order to provide quantitative estimates of the perceived benefits of vaccination and potential vaccine uptake.
DESIGN/METHODOLOGY/APPROACH: A discrete choice experiment (DCE) survey was developed to measure adolescent girls' preferences over features of HPV vaccines. The survey was fielded to a U.S. sample of 307 girls aged 13-17 years who had not yet received an HPV vaccine in June 2008.
FINDINGS: In a latent class logit model, two distinct groups were identified--one with strong preferences against vaccination which largely did not differentiate between vaccine features, and another that was receptive to vaccination and had well-defined preferences over vaccine features. Based on the mean estimates over the entire sample, we estimate that girls' valuation of bivalent and quadrivalent HPV vaccines ranged between $400 and $460 in 2008, measured as willingness-to-pay (WTP). The additional value of genital warts protection was $145, although cervical cancer efficacy was the most preferred feature. We estimate maximum uptake of 54-65%, close to the 53% reported for one dose in 2011 surveillance data, but higher than the 35% for three doses in surveillance data.
RESEARCH LIMITATIONS/IMPLICATIONS: We conclude that adolescent girls do form clear opinions and some place significant value on HPV vaccination, making research on their preferences vital to understanding the determinants of HPV vaccine demand.
ORIGINALITY/VALUE: DCE studies may be used to design more effective vaccine-promotion programs and for reassessing public health recommendations and guidelines as new vaccines are made available.

Related: USA

Nolte FS, Ribeiro-Nesbitt DG
Comparison of the Aptima and Cervista tests for detection of high-risk human papillomavirus in cervical cytology specimens.
Am J Clin Pathol. 2014; 142(4):561-6 [PubMed] Related Publications
OBJECTIVES: The Aptima and Cervista tests (Hologic/ Gen-Probe, San Diego, CA) were compared for detection of high-risk human papillomaviruses (HPV) in cervical cytology specimens.
METHODS: A total of 208 specimens were tested with both tests, and those with discordant results were tested with the Cobas HPV test (Roche Diagnostics, Indianapolis, IN). HPV test results were correlated with cytologic findings for all specimens and concurrent cervical biopsy specimens in 31 women.
RESULTS: The agreement between the results of the two tests was only 88% (McNemar test, P < .001). HPV was detected by both tests in 83 specimens, by Aptima alone in two, and by Cervista alone in 23. Both tests were negative in 100 specimens. One (50%) of two specimens positive by Aptima alone and only five (22%) of 23 specimens positive by Cervista alone were positive by the Cobas test. Of the 23 Cervista-positive/Aptima-negative specimens, 13 were positive in all three of the Cervista reaction mixtures for HPV clades A5/A6, A7, and A9, and 85% of these had high human genomic DNA fold-over-zero ratios (≥15).
CONCLUSIONS: We found poor positive percent agreement between the results of the Aptima and Cervista HPV tests and described an important source of false-positive Cervista results.

Related: Cancer Screening and Early Detection

Fitzpatrick P, O'Neill S, Mooney T, et al.
Age related influence on screening coverage and satisfaction. with CervicalCheck.
Ir Med J. 2014 Jul-Aug; 107(7):216-7 [PubMed] Related Publications
The aim of this study was to evaluate levels of satisfaction of women attending the CervicalCheck programme and reasons for the age differential in screening uptake. A questionnaire was sent to 5,000 randomly selected attenders with a normal smear test (3,500 aged 25-44, 1,500 aged 45-60). Almost all in both age groups said they would return to CervicalCheck if invited (98.5%; 98.5%) and recommend the service to family/friend (99.6%; 99.5%). The single independent predictor of 'would recommend to family/friend' was willingness to return to CervicalCheck (OR = 31 (5.2-183.7)). Predictors of 'would return if invited' were knowledge of when due to return (OR = 2.5 (1.3-5.0)) and having contacted or having received a letter of invitation from CervicalCheck (OR = 3.1 (1.6-6.1)). Independent predictors of 'knowledge of when due to return' were older age group (OR = 0.5 (0.4-0.7)) and willingness to return to CervicalCheck (OR = 3.2 (1.2-6.3)). The GP is particularly important in informing older women and encouraging attendance.

Related: Cancer Screening and Early Detection

Wan HY, Li QQ, Zhang Y, et al.
MiR-124 represses vasculogenic mimicry and cell motility by targeting amotL1 in cervical cancer cells.
Cancer Lett. 2014; 355(1):148-58 [PubMed] Related Publications
miRNAs have extensive functions in differentiation, metabolism, programmed cell death, and tumor metastasis by post-transcriptional regulation. Vasculogenic mimicry is an important pathway in tumor metastasis. Many factors can regulate vasculogenic mimicry, including miRNAs. In previous studies, miR-124 was found to repress proliferation and metastasis in different types of cancers, but whether it functions in cervical cancer remained unknown. Here, we demonstrate that miR-124 can repress vasculogenic mimicry, migration and invasion in HeLa and C33A cells in vitro. Furthermore, we reveal that the effect of miR-124 on vasculogenic mimicry, migration and invasion results from its interaction with AmotL1. MiR-124 regulates AmotL1 negatively by targeting its 3'untranslated region (3'UTR). We found that miR-124 can repress the EMT process. Together, these results improve our understanding of the function of miR-124 in tumor metastasis and will help to provide new potential target sites for cervical cancer treatment.

Related: MicroRNAs Angiogenesis and Cancer Signal Transduction

Xi LF, Schiffman M, Koutsky LA, et al.
Lineages of oncogenic human papillomavirus types other than type 16 and 18 and risk for cervical intraepithelial neoplasia.
J Natl Cancer Inst. 2014; 106(10) [PubMed] Article available free on PMC after 01/10/2015 Related Publications
BACKGROUND: Data on clinical outcomes of infection with variants of oncogenic human papillomavirus (HPV) types other than HPV16 and HPV18 are rare. We investigated intratypic variations in non-HPV16/18 oncogenic types and their corresponding relationships with cervical intraepithelial neoplasia grades 2-3 (CIN2/3).
METHODS: Study subjects were women who were positive for one or more of 11 non-HPV16/18 oncogenic types. Subjects were followed every six months for two years for detection of HPV and cervical lesions. Variant lineages were defined by sequencing the 3' part of the long control region and the entire E6/E7 region of HPV genome. Lineage-associated risk of CIN2/3 was assessed using logistic regression with generalized estimating equations.
RESULTS: A total of 4591 type-specific HPV infections among 2667 women were included in the analysis. The increase in risk of CIN2/3 was statistically significant for women with HPV31 A or B compared with C variants, HPV33 A1 compared with B variants, HPV45 A3 or B2 compared with B1 variants, HPV56 B compared with A2 variants, and HPV58 A1 or A3 compared with C variants. For these five types, the adjusted odds ratio associated with CIN2/3 was 2.0 (95% confidence interval [CI] = 1.5 to 2.6) for infections with single-type high-risk (HR) variants, 1.7 (95% CI = 1.0 to 2.7) for infections with two or more types but only one HR variant, and 5.3 (95% CI = 3.1 to 8.4) for infections with HR variants of two or more types as compared with those with single-type non-HR variants. The likelihood of CIN2/3 was similar for women with HPV16 infection and for those with HPV58 A1 variant infection.
CONCLUSIONS: These findings suggest that for a given HPV type, intratypic nucleotide changes may alter phenotypic traits that affect the probability of neoplasia.

Gillet VG, Solomon DH, Shadick NA, et al.
Behavioral and clinical factors associated with self-reported abnormal Papanicolaou tests in rheumatoid arthritis.
J Womens Health (Larchmt). 2014; 23(9):771-6 [PubMed] Article available free on PMC after 01/09/2015 Related Publications
BACKGROUND: Some evidence suggests that women with rheumatoid arthritis (RA) are at increased risk for the development of cervical cancer; however, it is unclear how this increase risk is conferred. We aimed to assess the factors related to abnormal Papanicolaou (Pap) tests in women with RA to determine whether they are similar to those reported for the general population.
METHODS: A structured questionnaire was mailed to 503 female patients from a longitudinal RA cohort. The survey included items on sociodemographic, behavioral, and gynecological factors. Univariate and multivariable logistic regression models examined the association of self-reported abnormal Pap results with a number of potential behavioral risk factors.
RESULTS: The questionnaire response rate was 57.5% (n=289). Median age was 61 years and 97% had ≥1 Pap test previously. Twenty-nine percent of respondents reported a previous abnormal Pap result. In the multivariable logistic model adjusted for age, number of lifetime sexual partners, age at menarche, birth control use, and history of sexually transmitted disease (STD), ever using birth control (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.18-4.52) and previous STD (OR 3.38, 95% CI 1.70-6.70) were associated with an increased risk of abnormal Pap result. Compared with either the state or national population, a greater proportion of the respondents was older, married, and previous smokers, and completed postsecondary education and obtained a Pap test.
CONCLUSIONS: In this cross-sectional study, self-reported abnormal Pap results were associated with use of birth control and history of STD in RA patients.

Darlin L, Borgfeldt C, Widén E, Kannisto P
Elderly women above screening age diagnosed with cervical cancer have a worse prognosis.
Anticancer Res. 2014; 34(9):5147-51 [PubMed] Related Publications
AIM: To analyze the cervical screening history in women with cervical cancer and their outcome.
DESIGN: All women diagnosed with cervical cancer between January 2009 and December 2010 in the South Sweden region were included in the audit.
MATERIALS AND METHODS: Cervical cancer was registered in 165 women in 2009 and 2010. Their screening history was analyzed, and was classified as normal or imperfect. The method of discovering the cancer was either by symptoms or by screening. The main outcome measured was overall survival in cervical cancer related to cervical screening history.
RESULTS: Women above 65 years of age were more frequently diagnosed with advanced-stage disease (The International Federation of Gynecology and Obstetrics II-IV) (n=36 out of 43; 84%) compared to women below 65 years of age (n=35 out of 122; 29%) (p<0.001). All patients diagnosed by the cervical screening program were still alive (30/30) at the median follow-up time (36 months), showing better overall survival compared to women below screening age in whom cancer was discovered due to symptoms (68/98; p<0.001). Cox proportional hazards model showed that women beyond screening age (>65 years old) with normal screening history had a worse prognosis, with a hazard ratio of 4.8 (95% confidence interval=1.9-12.1, p=0.001), and women (>65 years old) who had not followed the screening program had a hazard ratio of 5.9 (95% confidence interval I 2.4-14.6, p<0.001), compared to women under 65 years old who had followed the screening program.
CONCLUSION: Cervical cancer in women above the age of 65 years is discovered at advanced stages of the disease and their prognosis is poor.

Related: Cancer Screening and Early Detection

Mehlhorn G, Hautmann SK, Koch MC, et al.
HPV16-L1-specific antibody response is associated with clinical remission of high-risk HPV-positive early dysplastic lesions.
Anticancer Res. 2014; 34(9):5127-32 [PubMed] Related Publications
BACKGROUND/AIM: The present study was aimed at clarifying if use of a rapid human papillomavirus type 16 L1-specific antibody test could be used to improve clinical management of high-risk HPV-positive low-grade squamous intraepithelial lesion (LSIL)/high-grade squamous intraepithelial lesion (HSIL).
PATIENTS AND METHODS: The study was nested within a prospective study of 801 patients with early dysplastic high-risk HPV-positive lesions to examine the prognostic significance of HPV-L1 protein detection. Serum samples of 87 patients were tested with a rapid HPV16-L1-specific antibody test. The results were correlated with the clinical outcome during 66 months of follow-up.
RESULTS: A combined analysis of the 22 antibody-positive women showed that 17 were also L1 protein-positive, and 5 were L1 capsid protein-negative. An HPV-specific immune competence strongly correlates with clinical remission of low-grade squamous intraepithelial lesion (76.6%). For L1 antigen and HPV16-L1 antibody double-positive women, the risk of progression to cervical intraepithelial neoplasia grade 3 was low (5.8%).
CONCLUSION: The rapid anti-HPV16-L1 test could be a promising tool to improve risk assessment and appropriate clinical management of high-risk HPV-positive early dysplastic lesions.

Murakami N, Okamoto H, Kasamatsu T, et al.
A dosimetric analysis of intensity-modulated radiation therapy with bone marrow sparing for cervical cancer.
Anticancer Res. 2014; 34(9):5091-8 [PubMed] Related Publications
BACKGROUND/AIM: The purpose of the present study was to compare intensity-modulated radiation therapy (IMRT) plan with (Bone Marrow Sparing (BMS) - IMRT) or without (normal-IMRT) an intention of avoiding bone marrow in order to minimize treatment-related toxicity.
PATIENTS AND METHODS: Computed tomography (CT) images of 10 consecutive postoperative cervical cancer patients were used. All patients were already treated by normal-IMRT. BMS-IMRTs were created for this study and dose-volume histogram parameters were compared.
RESULTS: Both planning target volume (PTV) D95% and D97% were statistically lower in BMS-IMRT than normal-IMRT, however, the difference was lower than 3%. There were no statistical differences between BMS-IMRT and normal-IMRT in the mean value of rectum V30Gy, V50Gy; bladder V45Gy, V50Gy; Bowel V35Gy, and V50Gy. Both in whole pelvic bone (WPB) and inner cavity of pelvic bone (ICPB), the mean value of V10Gy, V30Gy, and V40Gy of BMS-IMRT were statistically lower than that of normal-IMRT.
CONCLUSION: Both lower and higher dose for WPB as well as ICPB were effectively lowered by BMS-IMRT.

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