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.
NCCC NCCC,founded in 1996,is a nonprofit organization dedicated to serving women with, or at risk for, cervical cancer and HPV disease. The NCCC has members around the world, and chapters across the U.S. The Website includes extensive resources.
healthtalkonline.org Detailed information, including snippets from interviews with 25 women, who share their experiences on a broad range of topics related to cervical cancer and treatment and side effects.
Foundation for Women's Cancer A non-profit organisation founded in 1991 to increase awareness and education, support expanded research and training, and provide knowledge and hope for women
diagnosed with cancers specific to them.
Jo's Cervical Cancer Trust A UK charity dedicated to women and their families affected by cervical cancer and cervical abnormalities. The Trust provides information, support, and promotes awareness of the importance of cervical screening.
PubMed Central search for free-access publications about Cervical Cancer MeSH term: Uterine Cervical Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Foundation for Women's Cancer A non-profit organisation founded in 1991 to increase awareness and education, support expanded research and training, and provide knowledge and hope for women
diagnosed with cancers specific to them.
SGO A professional membership organisation encouraging research, providing education, raising standards of practice, advocating for patients and members and collaborating with other domestic and international organizations. US + international members.
This list of publications is regularly updated (Source: PubMed).
Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013; 309(17):1793-802 [PubMed]
IMPORTANCE: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. OBJECTIVE: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. DESIGN, SETTING, AND PATIENTS: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). INTERVENTION: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. RESULTS: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. CONCLUSIONS AND RELEVANCE: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00501137.
Sachan R, Gupta P, Patel ML, et al. Cervical tuberculosis masquerading as cancer cervix: a report of three cases. Indian J Tuberc. 2013; 60(1):46-9 [PubMed]
Tuberculosis is still frequently observed in third world countries like Africa and Asia. Here we report three cases of genital tuberculosis with variable presentations. First case was a lady of reproductive age group who presented with polymenorrhea and post-coital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, post-coital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of tuberculosis but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital tuberculosis.
Renshaw AA, Elsheikh TM Assessment of manual workload limits in gynecologic cytology: reconciling data from 3 major prospective trials of automated screening devices. Am J Clin Pathol. 2013; 139(4):428-33 [PubMed]
Previous prospective studies have shown different results when comparing automated and manual screening of gynecologic cytology. The results of 3 large prospective studies were reviewed and relative sensitivity used as a gold standard. No significant differences could be shown in relative sensitivity between the ThinPrep Imaging System and the FocalPoint GS Imaging System (P > .05). When manual screening was restricted to less than 6 hours per day, 50 or fewer slides per day, and at least 6 minutes per slide (<10 slides/h), the relative sensitivity for automation was significantly lower for atypical squamous cells of undetermined significance and above (ASC+) (0.81; 95% confidence interval [CI], 0.79-0.83) than when manual screening was not restricted (1.07; 95% CI, 1.03-1.10). All 3 sites that screened 10 or more slides per hour manually had a relative sensitivity for automation that was significantly higher for high-grade squamous intraepithelial lesions and above (HSIL+) than for the remaining groups who screened less than 10 slides per hour (1.40 [95% CI, 1.22-1.60] vs 0.97 [95% CI, 0.95-1.00]). These results suggest that location finding of abnormalities (ASC+) may be more strongly associated with time spent screening per day, whereas classification/interpretation skills (HSIL+) may depend on time spent on an individual case. There is no evidence that automated screening devices are more sensitive than manual screening performed at lower well-defined workloads. More restricted workloads (≤41 slides/d, ≤4.5 h/d) for manual screening may perform significantly better than automated screening devices as measured by histologic cervical intraepithelial neoplasia 2 and above.
Carrigg A, Teschendorf C, Amaro D, et al. Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia. Am J Clin Pathol. 2013; 139(4):422-7 [PubMed]
At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.
Rai B, Patel FD, Chakraborty S, et al. Bladder-rectum spacer balloon in high-dose-rate brachytherapy in cervix carcinoma. Int J Radiat Oncol Biol Phys. 2013; 85(5):e217-22 [PubMed]
PURPOSE: To compare bladder and rectum doses with the use of a bladder-rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. METHODS AND MATERIALS: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm(3), 1-cm(3), 2-cm(3), 5-cm(3), and 10-cm(3) volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. RESULTS: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm(3), 1 cm(3), 2 cm(3), 5 cm(3), and 10 cm(3) and ICRU bladder point. Statistically significant dose reductions to 0.1-cm(3), 1-cm(3), and 2-cm(3) volumes for rectum were observed with the BRSB. No significant differences in 5-cm(3) and 10-cm(3) volumes and ICRU rectum point were observed. CONCLUSION: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of variable sizes are recommended for patients with a less spacious vaginal cavity.
Hasan TN, Shafi G, Syed NA, et al. Methanolic extract of Nigella sativa seed inhibits SiHa human cervical cancer cell proliferation through apoptosis. Nat Prod Commun. 2013; 8(2):213-6 [PubMed]
Nigella sativa (NS), also known as black cumin, has long been used in traditional medicine for treating various cancer conditions. In this study, we sought to investigate the potential anti-cancer effects of NS extract using SiHa human cervical cancer cells. NS showed an 88.3% inhibition of proliferation of SiHa human cervical cancer cells at a concentration of 125 microL/mL methanolic extract at 24 h, and an IC50 value 93.2 microL/mL. NS exposure increased the expression of caspase-3, -8 and -9 several-fold. The analysis of apoptosis by Dead End terminal transferase-mediated dUTP-digoxigenin end labeling (TUNEL) assay was used to further confirm that NS induced apoptosis. Thus, NS was concluded to induce apoptosis in SiHa cell through both p53 and caspases activation. NS could potentially be an alternative source of medicine for cervical cancer therapy.
Bishayee K, Ghosh S, Mukherjee A, et al. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: signal cascade and drug-DNA interaction. Cell Prolif. 2013; 46(2):153-63 [PubMed]
OBJECTIVES: Small aromatic compounds like flavonoids can intercalate with DNA molecules bringing about conformational changes leading to reduced replication and transcription. Here, we have examined one dietary flavonoid, quercetin (found in many fruit and vegetables), for possible anti-cancer effects, on HeLa cells originally derived from a case of human cervical cancer. MATERIAL AND METHODS: By circular dichroism spectroscopy we tested whether quercetin effectively interacted with DNA to bring about conformational changes that would strongly inhibit proliferation and migration of the HeLa cells. Cytotoxic effects of quercetin on cancer/normal cells, if any, were determined by MTT assay and such depolarization of mitochondrial membrane potential, as a consequence of quercetin treatment, and accumulation of reactive oxygen species (ROS) also were studied, by FACS analysis and expression profiles of different anti- and pro-apoptotic genes and their products were determined. RESULTS: Quercetin intercalated with calf thymus cell DNA and HeLa cell DNA and inhibition of anti-apoptotic AKT and Bcl-2 expression were observed. Levels of mitochondrial cytochrome-c were elevated and depolarization of mitochondrial membrane potential occurred with increase of ROS; upregulation of expression of p53 and caspase-3 activity were also noted. These alterations in signalling proteins and externalization of phosphotidyl serine residues were involved with initiation of apoptosis. Reduced AKT expression suggested reduction in cell proliferation and metastasis potential, with arrest of the cell cycle at G2/M. CONCLUSION: Quercetin would have potential for use in cervical cancer chemotherapy.
Laz TH, Rahman M, Berenson AB Human papillomavirus vaccine uptake among 18- to 26-year-old women in the United States: National Health Interview Survey, 2010. Cancer. 2013; 119(7):1386-92 [PubMed] Article available free on PMC after 01/04/2014
BACKGROUND: Human papillomavirus (HPV) vaccine uptake among young adult women has been reported to be very low. The authors conducted this study to provide an update on HPV vaccine uptake among 18- to 26-year-old women. METHODS: The authors used the National Health Interview Survey 2010 data to estimate HPV vaccine coverage and their correlates. RESULTS: Overall, 22.7% of women initiated (≥1 dose) and 12.7% completed the vaccine (≥3 doses). Thus, about 56% of women who initiated the vaccine completed it. Multivariate logistic regression analyses showed that younger age, unmarried status, Papanicolaou test, influenza vaccine, lifetime vaccines, and HPV vaccine awareness were positively associated with receiving ≥1 and ≥3 doses. In addition, uninsured women were less likely to receive ≥1 dose (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.28-0.84), and blacks (OR, 0.48; 95% CI, 0.23-0.99) and women with a family income <100% of the federal poverty level (OR, 0.40; 95% CI, 0.21-0.73) were less likely to receive ≥3 doses. Furthermore, based on vaccine initiators, blacks were less likely than whites to complete the vaccine (OR, 0.29; 95% CI, 0.16-0.55). Two thirds of unvaccinated women were not interested in future vaccination. Among those who were interested, >76.4% preferred to receive it free or at a lower cost, whereas 20% would pay the full cost of the vaccine. CONCLUSIONS: One in 8 women completed the 3-dose HPV vaccine. Educational and vaccine financing programs are needed to improve the uptake among low-income minority women who are at increased risk for cervical cancer.
Hamed AH, Shepard MK, Maglinte DD, et al. Neoadjuvant chemotherapy followed by simultaneous robotic radical trachelectomy and reversal of tubal sterilization in stage IB2 cervical cancer. JSLS. 2012 Oct-Dec; 16(4):650-3 [PubMed] Article available free on PMC after 01/04/2014
INTRODUCTION: The aim of this study was to report a case of cervical cancer stage IB2 treated with neoadjuvant chemotherapy, followed by simultaneous robotic-assisted radical trachelectomy and reversal of tubal sterilization. Case Description: This case occurred in a university hospital involving a 31-y-old woman with stage IB2 cervical cancer treated using neoadjuvant chemotherapy, robotic surgery, and tubal anastomosis to determine cancer disease status and achieve restoration of tubal patency. DISCUSSION: A successful radical trachelectomy with patent tubes was done bilaterally. Cancer and fertility procedures can be simultaneously implemented and achieved.
Hong DG, Park NY, Chong GO, et al. Laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy in patients with FIGO stage IB1-II B cervical carcinoma. JSLS. 2012 Apr-Jun; 16(2):229-35 [PubMed] Article available free on PMC after 01/04/2014
BACKGROUND AND OBJECTIVES: This study aimed to evaluate the safety, feasibility, and clinical outcomes of laparoscopic transperitoneal infrarenal para-aortic lymphadenectomy in patients with FIGO stage IB1-IIB cervical carcinoma. METHODS: Between August 1999 and April 2009, we performed 59 laparoscopic transperitoneal lymphadenectomies; specifically, 12 procedures were performed up to the level of the left renal vessels, and 47 procedures were performed up to the level of the inferior mesenteric artery. We retrospectively analyzed the pathology reports and clinical data and compared the 2 groups. The data were analyzed with a nonparametric Mann-Whitney test, Kaplan-Meier log-rank test, and Pearson's correlation analysis. RESULTS: The 2 groups did not significantly differ with respect to histologic type (P = .093), clinical stage (P = .053), tumor size (P = .383), time interval to start adjuvant therapy postoperatively (P = .064), and type of adjuvant therapy (P = .407). The blood loss (P = .131), operative time (P = .200), mean hospital stay (P = .417), and postoperative self-voiding (P = .306) did not significantly differ between the groups, with the exception of the number of harvested lymph nodes (P = .001). The disease-free survival was better in the group that underwent infrarenal para-aortic lymphadenectomy than the group that did not (P = .017); however, the 2 groups did not differ with respect to overall survival (P = .115). CONCLUSION: We suggest that laparoscopic transperitoneal infrarenal lymphadenectomy for cervical cancer is feasible and safe. The rate of positive lymph nodes in infrarenal lymphadenectomy is very rare in patients with locally advanced cervical carcinoma. Infrarenal lymphadenectomy in patients with cervical cancer did not provide additional survival benefits in this study.
Johansson C, Schwartz S Regulation of human papillomavirus gene expression by splicing and polyadenylation. Nat Rev Microbiol. 2013; 11(4):239-51 [PubMed]
Human papillomaviruses (HPVs) are small DNA tumour viruses that are present in more than 99% of all cervical cancers. The ability of these viruses to cause disease is partly attributed to the strict coordination of viral gene expression with the differentiation stage of the infected cell. HPV gene expression is regulated temporally at the level of RNA splicing and polyadenylation, and a dysregulated gene expression programme allows some HPV types to establish long-term persistence, which is a risk factor for cancer. In this Review, we summarize the role of splicing and polyadenylation in the regulation of HPV gene expression and discuss the viral and cellular factors that control these processes.
Durowade KA, Osagbemi GK, Salaudeen AG, et al. Prevalence and risk factors of cervical cancer among women in an urban community of Kwara State, north central Nigeria. J Prev Med Hyg. 2012; 53(4):213-9 [PubMed]
BACKGROUND: Cervical cancer is the second most common malignancy in women worldwide with a high incidence in under-developed countries and Nigeria is one of these countries. This study aimed at screening for cervical cancer using Papanicolaou smear and to identify risk factors for cervical cancer among women in Olufadi community, Kwara State, North-central Nigeria. METHODS: This was a cross-sectional study involving the screening of women aged 25-64 years for cervical cancer using Papanicolaou smear. Respondents were selected through systematic random sampling of households. Interviewer- administered questionnaire and clinical report form were also used to collect data. In addition, Pap smear samples were taken. Data was analyzed using SPSS version 15. RESULTS: Only 10 (5.0%) respondents had positive cytology result, while the rest were normal. Of the 10 positive cytology results, 1 (10.0%) was high grade squamous intraepithelial lesion (HGSIL) while the remaining 9 (90.0%) were low grade squamous intraepithelial lesion (LGSIL) which corresponds to 0.5% and 4.5% of the total respondents respectively. Risk factors for cervical cancer identified included coitarche, tobacco smoking, number of sexual partners and family history of cervical cancer. CONCLUSION: The findings from this study attest to the increasing burden of cervical cancer. The high number of positive results obtained from the study coupled with the presence of risk factors was an indication of how useful regular screening will be in the early detection of cervical cancer.
Ciszek B, Heimrath J, Ciszek M The application of human papilloma virus genotyping for the identification of neoplasm lesions in the cervix of women with abnormal cytology smears. Adv Clin Exp Med. 2012 Nov-Dec; 21(6):759-66 [PubMed]
BACKGROUND: A connection between infections with a highly oncogenic type of human papilloma virus and the development of cervical intraepithelial neoplasia and preinvasive cervical cancer has been proven both experimentally and clinically. The period after which persistent virus infection will lead to the development of precancerous and invasive lesions is dependent on, among others, the HPV genotype. The oncogenic types of human papilloma virus destabilize the genome of an infected cell and thus initiate the carcinogenesis process. OBJECTIVES: The aim of this work was to analyze the frequency of occurrence of different oncogenic HPV genotypes among women with abnormal cytological smears and the correlation of this data with the degree of cervical intraepithelial neoplasia exacerbation. MATERIAL AND METHODS: The sample consisted of 75 women of child-bearing age (16-43 years old) with an abnormal cytological smear and positive test identifying an infection with an oncogenic type of human papilloma virus. In every case histopathological verification, aimed at excluding pathologies in the endocervix, was conducted using a colposcopy with guided biopsy and cervix abrasion. RESULTS: The authors found that the frequency of occurrence of different HPV genotypes of the groups of cytological diagnoses ASC-US, LSIL and HSIL do not differ statistically (p = 0.57). However, what is noteworthy is the more common occurrence of HPV 16 in type LSIL lesions (45.45%) and HPV 18 of a more advanced type HSIL (37.50%) pathology. Through the verification of the cytology results with histopathological diagnosis of the above groups the authors obtained statistically significant differences (p < 0.001) of individual pathological states. When regarding cytological HSIL diagnosis, CIN 1 was never diagnosed, while in other cytological groups cervical intraepithelial neoplasia of a low degree constituted over 40%. Analogically about 40% of HSIL diagnoses after histopathological verification turned out to be cancer of a pre-invasive state (CIS/AIS), the presence of which was not revealed by ASC-US and LSIL. What is more, CIN2/3 diagnosis was less frequent in the ASC-US cytological group than in the other two groups. While analyzing a share of other than HPV 16 and HPV 18 oncogenic types of human papilloma virus, the authors found that the most common were HPV 31, 45 and 33. In CIN 1 and CIN 2 their share was over 60%. In CIS/AIS type pathologies, no other types of human papilloma virus than HPV 16 and HPV 18 were shown. CONCLUSIONS: Positive results of DNA HR HPV testing of women with abnormal cytology results identified a risk group for the development of cervical cancer. No statistically significant differences of the frequency of HPV 16 and HPV 18 type occurrences were found in analyzed groups with cytological and histopathological diagnoses.
Baalbergen A, Veenstra Y, Stalpers L Primary surgery versus primary radiotherapy with or without chemotherapy for early adenocarcinoma of the uterine cervix. Cochrane Database Syst Rev. 2013; 1:CD006248 [PubMed]
BACKGROUND: For early squamous cell carcinoma of the uterine cervix, the outcome is similar after either primary surgery or primary radiotherapy. There are reports that this is not the case for early adenocarcinoma (AC) of the uterine cervix: some studies have reported that the outcome is better after primary surgery. There are no systematic reviews about surgery versus chemoradiation in the treatment of cervical cancer. This is an updated version of the original Cochrane review published in Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD006248. DOI: 10.1002/14651858.CD006248. OBJECTIVES: The objectives of this review were to compare the effectiveness and safety of primary surgery for early stage AC of the uterine cervix with primary radiotherapy or chemoradiation. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2009, MEDLINE (1950 to July week 5, 2009), EMBASE (1980 to week 32, 2009) and we also searched the related articles feature of PubMed and the Web of Science. We also checked the reference lists of articles. For this update, the searches were re-run in June 2012: MEDLINE 2009 to June week 2, 2012, EMBASE 2009 to 2012 week 24, CENTRAL Issue 6, 2012, Cochrane Gynaecological Specialised Register June 2012. SELECTION CRITERIA: Studies of treatment of patients with early AC of the uterine cervix were included. Treatment included surgery, surgery followed by radiotherapy, radiotherapy and chemoradiation. DATA COLLECTION AND ANALYSIS: Forty-three studies were selected by the search strategy and 30 studies were excluded. Twelve studies were considered for inclusion. Except for one randomised controlled trial (RCT), all other studies were retrospective cohort studies with variable methodological quality and had limitations of a retrospective study. Comparing the results from these retrospective studies was not possible due to diverging treatment strategies. MAIN RESULTS: Analysis of a subgroup of one RCT showed that surgery for early cervical AC was better than radiotherapy. However, the majority of operated patients required adjuvant radiotherapy, which is associated with greater morbidity. Furthermore, the radiotherapy in this study was not optimal, and surgery was not compared to chemoradiation, which is currently recommended in most centres. Finally, modern imaging techniques (i.e. magnetic resonance imaging (MRI) and positive emission tomography - computed tomography (PET-CT) scanning) allow better selection of patients and node-negative patients can now be more easily identified for surgery, thereby reducing the risk of 'double trouble' caused by surgery and adjuvant radiotherapy. AUTHORS' CONCLUSIONS: We recommend surgery for early-stage AC of the uterine cervix in carefully staged patients. Primary chemoradiation remains a second best alternative for patients unfit for surgery; chemoradiation is probably first choice in patients with (MRI or PET-CT-suspected) positive lymph nodes. Since the last version of this review no new studies were found.
Gage JC, Schiffman M, Hunt WC, et al. Cervical histopathology variability among laboratories: a population-based statewide investigation. Am J Clin Pathol. 2013; 139(3):330-5 [PubMed]
To inform the proposed systematic adjudicative staining of cervical intraepithelial neoplasia grade 2 (CIN2) and equivocal diagnoses, we characterized diagnostic heterogeneity across 15 laboratories. Laboratory-specific distributions of 37,486 biopsy specimen diagnoses were compared after adjusting for preceding cytology. In a subset of preceding cytology specimens, HPV16 genotyping was considered an indicator of lesion severity. Distributions of normal and CIN1 diagnoses varied widely, with laboratories favoring either normal (5.5%-57.7%) or CIN1 diagnoses (23.3%-86.7%; P < .001 for normal:CIN1 variability). Excluding extreme values, 6.2% to 14.4% of diagnoses were CIN2 (P < .001). For CIN2 diagnoses, HPV16 positivity in the preceding cytology varied between 39.0% in the largest laboratory and 57.4% in others (P < .001), suggesting differential interpretation, not population differences, as a cause of variability. In conclusion, the frequency of diagnoses requiring special staining (p16(INK4a) immunostaining) to adjudicate equivocal CIN2 will be sizable and vary between laboratories, especially if extended to a fraction of CIN1 lesions.
Othman N, Othman NH Adequacy of cellular material in split-sampling of cervical scrapings for routine cancer screening: an analysis of 702 smears. Malays J Pathol. 2012; 34(2):115-21 [PubMed]
OBJECTIVE: The aim of this study was to examine cells (split-sample) that were retained on sampling devices used to collect conventional Pap smears (primary smears) in order to evaluate specimen adequacy and cytological diagnosis of scrapings that are routinely discarded. STUDY DESIGN: Cervical scrapings from women attending routine cervical cancer screening were obtained using a cervical brush. Following primary conventional smear preparation, the same sampling devices were rinsed in Preservcyt solution (Cytyc) for subsequent monolayered thin smear (split-sample/discarded sample). The smears (conventional and ThinPrep monolayer) were examined independently by pathologists and classified using the Bethesda System. The diagnoses from discarded samples (split-sample smears) were then compared with the diagnoses made on primary conventional Pap smears. RESULTS: 702 samples were studied. Cell abnormalities was found in 14/702 conventional smear and 12/702 split-sample thin smear. The adequacy of sampling in primary smears was 94.7% compared to 88.9% in split-sample smears. Six cases of Human Papillomavirus infection was found in split-sample smear, whereas only 5 cases found in primary smear. Cohen's Kappa was 0.61 showing substantial agreement between both sampling cytological results. CONCLUSION: The cervical brush discarded after conventional smear retain adequate number of cells for diagnostic purposes.
Han S, Li L, Jia X, et al. A molecular beacon-based method for screening cervical cancer. J Nanosci Nanotechnol. 2012; 12(11):8282-6 [PubMed]
The aim of this study is to develop a new screening method, molecular beacon (MB) imaging, for detection of cervical cancer and to determine its potential clinical applications by examining the sensitivity and specificity of target-specific MBs. Two target-specific molecular beacons were designed and synthesized for survivin and HPV16E6 mRNA. The two designed MBs and a random control MB were used to detect cervical cancer cell lines and a normal cell line. RT-PCR and western blot targeting survivin and HPV16E6 was done for verification. Furthermore the sensitivity and the specificity of the survivin and HPV16E6 mRNA MBs were examined in smears from 125 clinical cervical patients. The survivin and HPV16E6 mRNA MBs generated a strong fluorescence signal in cervical cancer cell lines, but not in the normal cell line, while the random control MB did not generated any signal in both cell lines. The fluorescence intensity correlated well with the gene expression levels in the cells determined by reverse transcription-PCR and Western blot analysis. The clinical sensitivity and the specificity of survivin MB-FITC were 72.5 and 77% while those of HPV16E6 MB-Cy3 were 96.1% and 71.6%, respectively. A parallel test of the two target MBs showed that the sensitivity increased to 98% and the specificity was 70.2%. The survivin and HPV16E6 mRNA MBs showed good reliability and sensitivity. They have great potential for clinical use in cervical cancer screening.
Wang S, Pang T, Gao M, et al. HPV E6 induces eIF4E transcription to promote the proliferation and migration of cervical cancer. FEBS Lett. 2013; 587(6):690-7 [PubMed]
Increasing evidence has placed eukaryotic translation initiation factor 4E (eIF4E) at the hub of tumor development and progression. Several studies have reported that eIF4E is over-expressed in cervical cancer; however, the mechanism remains elusive. The results of this study further confirm over-expression of eIF4E in cervical cancer tumors and cell lines, and we have discovered that the transcription of eIF4E is induced by protein E6 of the human papillomavirus (HPV). Moreover, regulation of eIF4E by E6 significantly influences cell proliferation, the cell cycle, migration, and apoptosis. Therefore, eIF4E emerges as a key player in tumor development and progression and a potential target for CC treatment and prevention.
Galarowicz B, Jach R, Kidzierska J, et al. The role of mRNA E6/E7 HPV high oncogenic risk expression in colposcopy of cervical intraepithelial neoplasia (CIN). Przegl Lek. 2012; 69(9):651-7 [PubMed]
UNLABELLED: The aim of this paper is the evaluation of colposcopy and mRNA E6/E7 HPV detection--as the marker of persistent human papilloma virus (HPV) infection in the triage of abnormal Pap smears and in the assessment of cervical intraepithelial neoplasia progression risk. The clinical material consisted of 85 women, participating the national cervical cancer screening in the period of April 2010, and October 2010, reffered to the Outpatient Clinic of Gynecologic Oncology and Female Genital Tract Neoplasms Prophylaxy of the Jagiellonian University Medical College in Krakow, Poland. All subjects were offered gynecological evaluation, Pap smear, colposcopy, DNA HPV (Hybrid Capture2, Qiagen) and mRNA E6/E7 testing (NulciSens, Biomerieux). In case of positive tests colposcopically directed cervical biopsy with histopathologic evaluation were performed. RESULTS: The presence of mRNA E6/E7 HPV transcripts correlated with high grade squamous intraepithelial lesions, statistically significantly. There was statistically difference between colposcopic, histologic concordance comparing to mRNA E6/E7 HPV colposcopic histologic concordance (p < 0.001). CONCLUSIONS: The presence of mRNA E6/E7 HR HPV may be assumed as specific marker of high grade cervical lesions. The combination of mRNA E6/E7 HR HPV ewith colposcopic evaluation increases the colposcopy concordanece with final histologic findings.
Jach R, Posadzka E, Sliwińska A, et al. The influence of surgery of cervical intraepithelial neoplasia (CIN) and cervical carcinoma on quality of life. Przegl Lek. 2012; 69(9):647-50 [PubMed]
UNLABELLED: The aim of the study was to determine to what extent cervical intraepithelial neoplasia and cervical cancer surgery affect a woman's mental state and how does it affect her interpersonal relationships, sexual activity, family life, and her professional and social activity. The clinical material consisted of 153 women aged 20 and 47, who were diagnosed and treated by the Chair of Gynaecology and Obstetrics, Jagiellonian University Medical College in Kraków between 2006 and 2010, and were confirmed to have CIN3 and cervical carcinoma stage IA. An oryginally constructed survey form consisting of 108 questions and divided into 5 research stages was implemented. H.J. Eysenck's Personality Questionnaire, and Physical and Mental State Questionnaire KS-40. RESULTS: The diagnosis generated a change in the patients' self-images: prior to the diagnosis, 74.6% considered themselves to be completely healthy, whereas after the diagnosis was given 40.5% of respondents had the feeling of illness, and 33.3% of the moderately illness. CONCLUSIONS: The diagnosis of CIN and microinvasive cervical cancer, and surgical procedure, invokes a feeling of being unwell in a woman who previously felt completely healthy, and significantly impedes quality of life. The diagnostic-therapeutic management induces general anxiety, worry about preservation of the generative organ, sexual intercourse, fertility, changes in the dynamics of the family and in the professional field, as well as changes in interpersonal relationships.
Markman M Chemoradiation in the management of cervix cancer: current status and future directions. Oncology. 2013; 84(4):246-50 [PubMed]
Cytotoxic chemotherapy has been shown to have only a very modest impact on outcome in recurrent, persistent, or metastatic cervix cancer. Despite this fact, when cisplatin is administered concurrently with external beam radiation as a 'chemosensitizing' strategy, both progression-free and overall survival have been shown in multiple evidence-based randomized trials to be improved compared to the delivery of radiation alone. Ongoing research in this area has focused on improving the drug component of this strategy and on following the concurrent chemoradiation with systemic ('adjuvant') therapy.
Harris M, Wang XG, Jiang Z, et al. Combined treatment of the experimental human papilloma virus-16-positive cervical and head and neck cancers with cisplatin and radioimmunotherapy targeting viral E6 oncoprotein. Br J Cancer. 2013; 108(4):859-65 [PubMed] Article available free on PMC after 05/03/2014
Background:Human papilloma virus (HPV) is implicated in >99% of cervical cancers and ∼40% of head and neck squamous cell carcinoma (HNSCC). We previously targeted E6 oncogene with (188)Rhenium-labelled monoclonal antibody (mAb) C1P5 to HPV16 E6 in cervical cancer and HNSCC. Intranuclear E6 can be accessed by mAbs in non-viable cells with leaky membranes. As radioimmunotherapy (RIT) efficacy depends on the availability of target protein-we hypothesised that pretreatment with cisplatin will kill some tumour cells and increase E6 availability for RIT.Methods:Mice with subcutaneous HPV16+ cervical (CasKi) and HNSCC (2A3) tumours were pretreated with 0-7.5 mg kg(-1) per day cisplatin for 3 days followed by (188)Re-C1P5 and biodistribution was performed 24 h later. For RIT, the animals were treated with: 5 mg kg(-1) per day cisplatin for 3 days; or 5 mg kg(-1) per day cisplatin for 3 days followed 200 or 400μCi (188)Re-C1P5 mAb; or 200 or 400μCi (188)Re-C1P5 mAb; or left untreated, and observed for tumour growth for 24 days.Results:Pretreatment with cisplatin increased the uptake of (188)Re-C1P5 in the tumours 2.5 to 3.5-fold and caused significant retardation in tumour growth for CasKi and 2A3 tumours in both RIT alone and cisplatin, and RIT groups in comparison with the untreated control and cisplatin alone groups (P<0.05). The combined treatment was more effective than either modality alone (P<0.05).Conclusion:Our study demonstrates that preceding RIT targeting E6 oncogene with chemotherapy is effective in suppressing tumour growth in mouse models of HPV16+ cancers.
Smith RA, Brooks D, Cokkinides V, et al. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. CA Cancer J Clin. 2013 Mar-Apr; 63(2):88-105 [PubMed]
Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are updated guidelines on cervical cancer screening and lung cancer screening with low-dose helical computed tomography. The latest data on the use of cancer screening from the National Health Interview Survey also are described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act of 2010.
Booth CN, Bashleben C, Filomena CA, et al. Monitoring and ordering practices for human papillomavirus in cervical cytology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 5. Arch Pathol Lab Med. 2013; 137(2):214-9 [PubMed]
CONTEXT: The association of certain types of human papillomavirus with cervical carcinoma is well established. Human papillomavirus testing is now routinely used to screen for cervical carcinoma and precursor lesions of the cervix (cotesting and reflex testing) and these results are considered in patient triage and management. OBJECTIVE: To provide information about current laboratory practices in human papillomavirus testing and consensus best practice statements based on results from the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. DESIGN: The College of American Pathologists submitted a paper-based survey to 1245 laboratories in the United States. After review of the initial results, follow-up Web-based survey results, and a literature review by an expert working group, consensus best practice statements were constructed by working group members for presentation at a national consensus conference. These best practice statements were discussed and then voted upon by conference participants. RESULTS: A total of 525 laboratories responded to survey questions about human papillomavirus ordering and monitoring practices, whereas 546 responded to the overall survey. In most laboratories (87.6%), the high-risk human papillomavirus test is ordered as a reflex test by providers. A minority of laboratories (11.9%) routinely bundle low- and high-risk human papillomavirus tests. Most laboratories (84.4%) do not limit testing in patients with atypical squamous cells to women older than 20 years. More than half of laboratories (53.3%) monitor human papillomavirus positive rates in Papanicolaou tests with atypical squamous cells of undetermined significance. CONCLUSIONS: It is not appropriate for laboratories to offer low-risk human papillomavirus testing for any clinical circumstance in gynecologic cytology. Laboratories should not order human papillomavirus testing to resolve diagnostic discrepancies. It is a valuable broad measure of laboratory quality to monitor the human papillomavirus-positive rates in Papanicolaou tests with atypical squamous cells.
McCann GA, Boutsicaris CE, Preston MM, et al. Neuroendocrine carcinoma of the uterine cervix: the role of multimodality therapy in early-stage disease. Gynecol Oncol. 2013; 129(1):135-9 [PubMed]
BACKGROUND: Neuroendocrine carcinomas (NECs) of the cervix comprise only 2% of all cervical cancers. Prospective data is limited and treatment guidelines rely on retrospective reviews and literature from lung NEC. The objective of this study was to report our experience in the management of this rare disease. METHODS: This was an IRB-approved retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990 and 2012. Demographic, treatment and survival data was collected. Progression free survival (PFS) and overall survival (OS) were assessed. RESULTS: Twenty-six patients met inclusion criteria. Advanced-stage disease (II-IV) was diagnosed in 58% (n=15) of patients. Of the eleven patients with stage I disease, five were treated with platinum-based neoadjuvant chemotherapy (NACT), six with initial radical surgery, and seven received adjuvant therapy including chemotherapy and/or radiation. Nine patients (82%) are currently without evidence of disease (NED). Patients with stage I disease had significantly improved PFS and OS compared to stages II-IV with a median OS that was not reached and 12.1 months, respectively (p=0.0013). The majority of stage I patients with lymph node metastasis and large tumors achieved durable remission with triple-modality therapy including NACT and surgery followed by adjuvant therapy. CONCLUSIONS: Cervical NEC is an aggressive disease associated with a high mortality rate. Patients with advanced-stage disease have a poor prognosis regardless of therapy. However, multimodality with consideration of triple-modality therapy in early-stage disease has the potential for complete response and long-term survival, supporting the goal of curative intent in these patients.
Singh RB, Chander S, Mohanti BK, et al. Neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma: a pilot study. Gynecol Oncol. 2013; 129(1):124-8 [PubMed]
OBJECTIVE: To evaluate role of dose dense neo-adjuvant chemotherapy (NACT) prior to standard concurrent chemo-radiation (CCRT) in locally advanced cervical cancer. METHODS: Between June 2010 and December 2011, 28 patients (median age - 51 years, range, 35 to 67 years) with locally advanced cervical cancer received NACT using paclitaxel (60 mg/m(2)) and carboplatin (AUC-2) weekly for 6 doses. After a mean interval of 15 days (range 7-23 days), the patients then received definitive radiation and concomitant weekly infusion of cisplatin (40 mg/m(2) for 6 doses). Response to concurrent chemo-radiation and toxicity were end points. RESULTS: Following NACT, 67.8% of patients responded; complete (CR) - 2(7.1%), Partial (PR) - 17 (60.7%), stable 7 (25.0%) and 2 patients (7.1%) progressed. 24 of 28 patients received CCRT; 23/24 achieved CR. 22 of 23 complete responders continue to be in CR at a median follow-up of 12 months (range, 7 to 24 months). Grade III/IV neutropenia was the main hematological toxicity seen in 28.5% and 29% of patients, respectively during NACT and CCRT. CONCLUSIONS: Neoadjuvant chemotherapy with dose dense weekly paclitaxel and carboplatin followed by standard CCRT is a feasible approach and is associated with a high response rate in locally advanced cervical cancer.
Hagemann AR, Wilkinson-Ryan I, Kuroki LM, Squires K Discussion: 'Comparison of cervical cancer screening strategies,' by Cox et al. Am J Obstet Gynecol. 2013; 208(3):e1-4 [PubMed]
In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research.
Hemida R, Goda H, Abdel-Hady el-S, El-Ashry R Embryonal rhabdomyosarcoma of the female genital tract: 5 years' experience. J Exp Ther Oncol. 2012; 10(2):135-7 [PubMed]
OBJECTIVES: To present our single institution experience with 10 cases of embryonal rhabdomyosarcoma diagnosed over 5 years. METHODS: Retrospective analysis of the medical records of 10 patients. The initial presenting data as age, complains and staging were analyzed. Surgical interference of all cases was studied. The follow up data regarding survival and recurrences were analyzed. RESULTS: The mean age at diagnosis was 4.3 years (range: 2-12). Six cases (60%) were subjected to "True Cut" biopsy and 4 cases (40%) were subjected to complete surgical excision of the tumor. All cases received chemotherapy. "Vincristine, Actinomycin D, Cyclophosphamide" combination was the most commonly used. Radiation therapy was used in 3 patients (30%) in the form of external beam radiation. The 5-year overall survival of our studied cases were 80%. CONCLUSION: The recurrence rate of our retrospectively studied 10 cases of embryonal rhabdomyosarcoma of vagina and cervix was high (70%). However, five-year survival was 80%. Combined modality treatment is essential to improve prognosis.
Li RF, Gupta M, McCluggage WG, Ronnett BM Embryonal rhabdomyosarcoma (botryoid type) of the uterine corpus and cervix in adult women: report of a case series and review of the literature. Am J Surg Pathol. 2013; 37(3):344-55 [PubMed]
In its classical form, embryonal rhabdomyosarcoma (ERMS, botryoid type) is a vaginal neoplasm occurring in infants and young girls and is often not considered in the differential diagnosis of uterine corpus and cervical spindle cell tumors in adult women. Clinicopathologic and immunohistochemical features of 25 cases of ERMS in women 20 years of age or older were analyzed. Patient age ranged from 20 to 89 years (mean, 44.4 y; median, 46 y), with 8 patients aged 20 to 39 years, 14 patients aged 40 to 59 years, and 3 patients older than 60 years of age. Tumors originated in the cervix in 20 cases and in the uterine corpus in 5. They were characterized by an edematous hypocellular spindle cell proliferation, typically with cellular condensation beneath epithelial surfaces (cambium layer), in which tightly packed hypercellular foci were scattered. Neoplastic cells had hyperchromatic nuclei and minimal cytoplasm, usually with delicate cytoplasmic processes. Occasionally, elongated or globular cells with eosinophilic cytoplasm (rhabdomyoblasts) were evident, but cytoplasmic cross-striations were only rarely identified. Apoptotic bodies and mitotic figures were usually identified in the hypercellular foci. Hemorrhage was common, often making recognition of the hypercellular foci difficult. Desmin and myogenin were coexpressed in 22 of 23 (95.6%) tumors evaluated. Proliferative activity, as assessed by Ki-67 expression, was notably elevated in all tumors evaluated, typically concentrated in the hypercellular foci. Estrogen and progesterone receptors were expressed focally in only 3 of 12 (25%) and 1 of 8 (12.5%) tumors evaluated, respectively. Follow-up was available in 7 cases. Five patients were alive without evidence of disease with follow-up of 3 to 8 years, and 1 patient was alive with disease at 5 months. One patient died at 5 months with pulmonary nodules, but it was not determined whether this was due to metastatic ERMS or the patient's known ductal breast carcinoma. ERMS has a broader clinical profile than classically expected and should be considered in the differential diagnosis of a uterine corpus or cervical spindle cell tumor, regardless of patient age. Recognition can be rendered difficult by the hypocellular background, which can suggest a benign polyp or low-grade tumor, and hemorrhage, which can obscure the characteristic hypercellular foci. Identification of hypercellular foci in which mitotic activity and apoptotic bodies are found, desmin and myogenin are coexpressed, proliferative activity is notably elevated, and hormone receptor expression is usually absent is very useful for establishing the diagnosis.
Downey K, Riches SF, Morgan VA, et al. Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images. AJR Am J Roentgenol. 2013; 200(2):314-20 [PubMed]
OBJECTIVE: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.
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