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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.
In the UK about 2,800 women are diagnosed with cervical cancer each year. (Source: Cancer Research UK)
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MeSH term: Uterine Cervical Neoplasms
US National Library of Medicine
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Showing publications with corresponding authors from the UK (Source: PubMed).
Knowledge of Greek adolescents on human papilloma virus (HPV) and vaccination: A national epidemiologic study.
Medicine (Baltimore). 2017; 96(1):e5287 [PubMed] Free Access to Full Article Related Publications
Improving outcomes for older women with gynaecological malignancies.
Cancer Treat Rev. 2016; 50:99-108 [PubMed] Related Publications
Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia.
Obstet Gynecol. 2016; 127(2):353-9 [PubMed] Related Publications
METHODS: A retrospective case series including all patients with CIN treated with trichloroacetic acid as first-line therapy was performed. Treatment response was evaluated by colposcopy, cervical biopsy, cytology, and type-specific human papillomavirus (HPV) testing 8 weeks after a single trichloroacetic acid treatment. Regression was defined as improvement from high-grade to low-grade CIN and remission was defined as improvement from any grade of CIN to no CIN. For quantification of treatment-related pain, 107 (44.1%) patients rated their subjective perception on a visual analog scale.
RESULTS: A total of 241 women were included in the study with 179 high-grade (CIN 2-3) and 62 low-grade (CIN 1) squamous intraepithelial lesions. For high-grade squamous intraepithelial lesions, the histologic regression rate was 87.7% (95% confidence interval [CI] 82.0-92.1) and the remission rate was 80.3% (95% CI 73.3-85.5). For low-grade squamous intraepithelial lesions, the remission rate was 82.3% (95% CI 70.5-90.8). Human papillomavirus types 16 and 18 were found in 53.7% and 7.3% of all women tested, respectively. Clearance rates of HPV type 16 and HPV type 18 were 73.5% (95% CI 62.5-81.3) and 75.0% (95% CI 46.2-95.0), respectively. Median pain score was 3.0 out of 10.0 (25th and 75th percentiles 2.3 and 4.3, respectively). There were no major side effects observed during treatment or follow-up.
CONCLUSION: A high regression and remission rate and a high HPV clearance rate were observed 8 weeks after topical 85% trichloroacetic acid treatment for patients with CIN.
Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors.
Int J Gynecol Cancer. 2016; 26(4):763-9 [PubMed] Related Publications
Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study.
Int J Radiat Oncol Biol Phys. 2016; 94(5):1088-98 [PubMed] Related Publications
METHODS AND MATERIALS: In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population.
RESULTS: General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea).
CONCLUSIONS: This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of reference data. Several tumor-related symptoms resolved after treatment, and functioning and general QoL returned to that of the level of the reference population, indicating a transient impact of diagnosis and treatment. However, several treatment-related symptoms and problems did develop and persist, either immediately or gradually after treatment.
Use of HPV testing for cervical screening in vaccinated women--Insights from the SHEVa (Scottish HPV Prevalence in Vaccinated Women) study.
Int J Cancer. 2016; 138(12):2922-31 [PubMed] Related Publications
The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.
PLoS One. 2016; 11(1):e0147029 [PubMed] Free Access to Full Article Related Publications
METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).
CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.
HPV testing for primary cervical screening: Laboratory issues and evolving requirements for robust quality assurance.
J Clin Virol. 2016; 76 Suppl 1:S22-8 [PubMed] Related Publications
Advances and Concepts in Cervical Cancer Trials: A Road Map for the Future.
Int J Gynecol Cancer. 2016; 26(1):199-207 [PubMed] Free Access to Full Article Related Publications
METHODS: The focus was to develop a consensus on several concepts for future clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps in need of new evidence, validating control arms for present and future clinical trials and identifying national and international barriers for studies of cervix cancers. The second half of the meeting was concerned with achieving consensus on a path forward.
RESULTS AND CONCLUSIONS: There were 5 principal outcomes as follows: first, a proposal to expand fertility-preserving options with neoadjuvant chemotherapy; second, validation of the assessment of sentinel lymph nodes using minimally invasive surgery with an emphasis on identification and management of low-volume metastasis, such as isolated tumor cells and micrometastasis; third, evaluation of hypofractionation for palliative and curative radiation under the umbrella of the GCIG Cervix Cancer Research Network; fourth, adding to the advances in antiangiogenesis therapy in the setting of metastatic disease; and fifth, developing a maintenance study among women at high risk of relapse. The latter 2 systemic interventions could study PI3K (phosphatidylinositol-3-kinase) inhibitors, immunotherapy, anti-human papillomavirus approaches, or novel antiangiogenic agents/combinations.
Reprint of "Cancer of the cervix: A sexually transmitted infection?".
Cancer Epidemiol. 2015; 39(6):1148-51 [PubMed] Related Publications
Influence of Spirituality and Modesty on Acceptance of Self-Sampling for Cervical Cancer Screening.
PLoS One. 2015; 10(11):e0141679 [PubMed] Free Access to Full Article Related Publications
METHODOLOGY: We enrolled 600 participants in Nigeria between August and October 2014 and collected information on spirituality and modesty using two scales. We used principal component analysis to extract scores for spirituality and modesty and logistic regression models to evaluate the association between spirituality, modesty and preference for self-sampling. All analyses were performed using STATA 12 (Stata Corporation, College Station, Texas, USA).
RESULTS: Some 581 (97%) women had complete data for analysis. Most (69%) were married, 50% were Christian and 44% were from the south western part of Nigeria. Overall, 19% (110/581) of the women preferred self-sampling to being sampled by a health care provider. Adjusting for age and socioeconomic status, spirituality, religious affiliation and geographic location were significantly associated with preference for self-sampling, while modesty was not significantly associated. The multivariable OR (95% CI, p-value) for association with self-sampling were 0.88 (0.78-0.99, 0.03) for spirituality, 1.69 (1.09-2.64, 0.02) for religious affiliation and 0.96 (0.86-1.08, 0.51) for modesty.
CONCLUSION: Our results show the importance of taking cultural and religious beliefs and practices into consideration in planning health interventions like cervical cancer screening. To succeed, public health interventions and the education to promote it must be related to the target population and its preferences.
Risk Stratification Using Human Papillomavirus Testing among Women with Equivocally Abnormal Cytology: Results from a State-Wide Surveillance Program.
Cancer Epidemiol Biomarkers Prev. 2016; 25(1):36-42 [PubMed] Free Access to Full Article Related Publications
METHODS: Kaplan-Meier and logistic-Weibull survival models were used to estimate cumulative risks of CIN3(+) among women ages 21 to 64 who were screened in New Mexico between 2007 and 2011 with negative, equivocal or mildly abnormal cytology, that is, atypical squamous cells of undetermined significance (ASC-US; with or without HPV triage), or low-grade squamous intraepithelial lesions (LSIL).
RESULTS: We identified 452,045 women meeting the selection criteria. The 3-year CIN3(+) risks for women with negative, ASC-US, and LSIL cytology were 0.30%, 2.6%, and 5.2%, respectively. HPV triage of ASC-US stratified 3-year CIN3(+) risks were 0.72% for HPV-negative and 7.7% for HPV-positive. Risks tended to decline after age 30 for all screening results.
CONCLUSIONS: In this state-wide population-based cohort, cytology and HPV triage of ASC-US stratified women's CIN3(+) risk into similar patterns observed previously, suggesting the validity of screening guidelines for diverse populations in the United States. Absolute risk estimates should be compared across other large populations.
IMPACT: Strategies for HPV triage of ASC-US derived from clinical trials are upheld in large clinical practice settings and across diverse screening populations in the United States.
Perspectives on cervical cancer screening among educated Muslim women in Dubai (the UAE): a qualitative study.
BMC Womens Health. 2015; 15:90 [PubMed] Free Access to Full Article Related Publications
METHODS: Interpretivist and social constructivist epistemological approaches were applied for this qualitative study. Data were obtained through 13 in-depth interviews. Purposive and snowballing methods were used to recruit six South Asian women and seven Emirati women living in Dubai. Thematic content analysis was concurrently applied with comparative analysis to the data.
RESULTS: Four themes regarding women's perceptions of CC emerged from the data. First, CC was considered a 'silent disease' that could be detected with early screening. However, it was also associated with extramarital sexual relations, which negatively influenced screening uptake. Second, women's fear, pain and embarrassment, along with cultural influences, deterred them from undergoing screening. Third, a growing mistrust of allopathic medicine and impersonal healthcare promoted a negative view of screening. Last, women became aware of screening mainly when they were pregnant or receiving fertility treatment.
CONCLUSIONS: The study highlighted a number of important factors relating to cultural, religious and sexual behaviour that shaped educated Muslim women's perspectives on CC screening. Evidently, the current opportunistic approach to screening is flawed. A national awareness programme on CC screening should be developed, tailored to the sociocultural norms of the Muslim community, to promote knowledge regarding the causes of CC and the importance of screening.
Cancers in Australia in 2010 attributable to and prevented by the use of combined oral contraceptives.
Aust N Z J Public Health. 2015; 39(5):441-5 [PubMed] Free Access to Full Article Related Publications
METHODS: We estimated the population attributable fraction (PAF) for cancers causally associated with combined OCP use (breast, cervix), and the proportion of endometrial and ovarian cancers prevented (prevented fraction [PF]). We used standard formulae incorporating prevalence of combined OCP use in the Australian population, relative risks of cancer associated with this exposure and cancer incidence.
RESULTS: An estimated 105 breast and 52 cervical cancers (0.7% and 6.4% of each cancer, respectively) in Australia in 2010 were attributable to current use of combined OCP. Past combined OCP use was estimated to have prevented 1,032 endometrial and 308 ovarian cancers in 2010, reducing the number of cancers that would otherwise have occurred by 31% and 19%, respectively.
CONCLUSIONS: A small proportion of breast and cervical cancers is attributable to combined OCP use; OCP use is likely to have prevented larger numbers of endometrial and ovarian cancers.
IMPLICATIONS: Women seeking contraceptive advice should be told of potential adverse effects, but should also be told that - along with reproductive health benefits - combined OCP use can reduce long-term risks of ovarian and endometrial cancers.
Dysregulation of host cellular genes targeted by human papillomavirus (HPV) integration contributes to HPV-related cervical carcinogenesis.
Int J Cancer. 2016; 138(5):1163-74 [PubMed] Free Access to Full Article Related Publications
The PapilloCheck Assay for Detection of High-Grade Cervical Intraepithelial Neoplasia.
J Clin Microbiol. 2015; 53(11):3553-9 [PubMed] Free Access to Full Article Related Publications
Location of Sentinel Lymph Node in Cervical Carcinoma and Factors Associated With Unilateral Detection.
Int J Gynecol Cancer. 2015; 25(9):1663-8 [PubMed] Related Publications
METHODS: This was a retrospective review of SLN data (anatomical location, count and laterality) in patients with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA1 with lymphovascular space invasion to stage IIA) using intraoperative gamma probe and blue dye. The preoperative single-photon emission computed tomography with computed tomography was used to detect laterality, number of the SLNs, and rare locations. Patients were treated between January 2005 to January 2015 at the West Kent Gynaecological Oncology Centre, Maidstone Hospital, Maidstone, United Kingdom.
RESULTS: A total of 132 women were investigated. The most common SLN location was the external iliac (38.6%) followed by obturator (25.3%) and internal iliac (23.6%) regions. A small percentage was identified in presacral (1.4%) and para-aortic regions (0.7%). Older age (P = 0.01) and an elevated body mass index (P = 0.03) were associated with decreased SLN count by preoperative single-photon emission computed tomography with computed tomography, and only age affected SLN count by gamma probe (P = 0.01). Initial surgery, large loop excision of the transformation zone, or cone biopsy of the cervix had no effect on SLN count. There was no difference observed in bilateral detection with respect to surgical approach (open: n = 48/laparoscopic: n = 84). However, older age was independently associated with a decrease in bilateral SLN detection (P = 0.003). In these patients who underwent unilateral full pelvic lymphadenectomy, all the nonsentinel nodes were negative.
CONCLUSIONS: The majority of SLNs were located in the external iliac, obturator, and internal iliac regions. Both older age and an elevated body mass index were associated with a reduced SLN count. Unilateral detection of SLN was independently associated with older age, which may be due to sclerosis in the lymphatic vessels or reduced perfusion in the pelvis in these women. If no SLN is detected on one side, the consensus is to perform a full pelvic lymphadenectomy on that side of the pelvis.
DAPK1 Promoter Methylation and Cervical Cancer Risk: A Systematic Review and a Meta-Analysis.
PLoS One. 2015; 10(8):e0135078 [PubMed] Free Access to Full Article Related Publications
METHODS: A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source.
RESULTS: A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14-40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83-36.78). The association was also confirmed in all the subgroups analyses.
CONCLUSIONS: A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus.
Pathological Risk Factors and Outcomes in Women With Stage IB2 Cervical Cancer Treated With Primary Radical Surgery Versus Chemoradiotherapy.
Int J Gynecol Cancer. 2015; 25(8):1476-83 [PubMed] Related Publications
METHODS: We performed a retrospective study of 92 women with stage IB2 cervical cancer who were treated at the Northern Gynecological Oncology Center (Gateshead, United Kingdom) across a 22-year period between January 1991 and July 2013. Women were divided into those undergoing primary surgery and those undergoing primary radiotherapy/chemoradiotherapy. The main outcome measures were OS and progression-free survival (PFS). Pathological risk factors of survival were assessed using multivariate analysis.
RESULTS: Sixty-seven women (72.8%) underwent primary surgery, and 25 women (27.2%) had primary radiotherapy/chemoradiotherapy. Thirty-one of 67 women (46.3%) required adjuvant radiotherapy/chemoradiotherapy after surgery because of positive lymph nodes in 77.4% of cases. The median follow-up was 57.5 months (range, 3-137 months). Thirty-two women (34.8%) had disease recurrence: 6 women (16.7%) in the group undergoing surgery alone, 15 women (48.4%) in the group requiring adjuvant treatment after surgery, and 11 women (44%) in the group having primary radiotherapy/chemoradiotherapy. Overall survival and PFS were higher for women undergoing surgery alone (91.7% and 83.3%) compared with women requiring adjuvant treatment after surgery (54.8% and 51.4%) and those having primary radiotherapy/chemoradiotherapy (60% and 56%) (P = 0.0004 and P = 0.005, respectively). Lymph node metastasis was a significant pathological risk factor of OS and PFS in multivariate analysis.
CONCLUSIONS: Most women require adjuvant treatment after surgery because of positive lymph nodes. Because survival outcomes for women requiring dual treatment are similar to those for women undergoing primary chemoradiotherapy, nodal assessment before definitive treatment should guide the management of these women and identify a low-risk group that can be treated with surgery alone.
A multicenter study to quantify systematic variations and associated uncertainties in source positioning with commonly used HDR afterloaders and ring applicators for the treatment of cervical carcinomas.
Med Phys. 2015; 42(8):4472-83 [PubMed] Related Publications
METHODS: Eighty-six rings from 20 European brachytherapy centers were audited in the form of a postal audit with each center collecting the data independently. The data were collected by setting up the rings using a bespoke jig and irradiating gafchromic films at predetermined dwell positions using four afterloader types, MicroSelectron, Flexitron, GammaMed, and MultiSource, from three manufacturers, Nucletron, Varian, and Eckert & Ziegler BEBIG. Five different ring types in six sizes (Ø25-Ø35 mm) and two angles (45° and 60°) were used. Coordinates of irradiated positions relative to the ring center were determined and collated, and source position differences quantified by ring type, size, and angle.
RESULTS: The mean expanded measurement uncertainty (k = 2) along the direction of source travel was ±1.4 mm. The standard deviation associated with the source position reproducibility was within ±1.0 mm for all afterloaders. Maximum source positional variations of 2.1 and 3.9, 1.8 and 5.4, and 2.3 and 3.4 mm were observed at standard treatment positions for the Ø26, Ø30, and Ø32 mm sized 45° and 60° rings, respectively. Mean positional differences between a majority of the rings were within ±1.0 mm. Mean positional differences between a majority of the intracenter ring sets were within the expanded measurement uncertainty. When comparing the 45°-60° source paths, mean differences of 1.6, 0.9, and 0.9 mm were observed across the Ø26, Ø30 (MicroSelectron), and Ø32 mm (GammaMed) rings, respectively. When comparing to manufacturer source path models, maximum offsets of 1.9 and 2.1, 2.6 and 2.3, and 0.8 and 1.6 mm were observed for the Ø26, Ø30 (MicroSelectron), and Ø30 mm (Flexitron) sized 45° and 60° rings, respectively. When comparing the audit to ring commissioning data of participating centers, mean differences of up to 2.4 mm were observed.
CONCLUSIONS: A majority of the audited rings showed a good degree of manufacturer consistency; however, substantial positional variation observed between some rings emphasizes the importance of commissioning each ring before clinical use. Differences observed between audit and commissioning data also indicate some variation in source treatment positions across centers.
The Participation of HPV-Vaccinated Women in a National Cervical Screening Program: Population-Based Cohort Study.
PLoS One. 2015; 10(7):e0134185 [PubMed] Free Access to Full Article Related Publications
METHODS: A cohort of all women resident in Sweden, born 1977-1987 (N=629,703), and invited to cervical screening, was followed October 2006 - December 2012. Invitations to screening were identified via the National Quality Register for Cervical Cancer Prevention, as was the primary outcome of a registered smear. Vaccination status was obtained from two nationwide health data registers. Hazard ratios (HR) were estimated using Cox regression adjusted for age, education level and income (HRadj). Women were individually followed for up to 6 years, of which the first and second screening rounds were analyzed separately.
RESULTS: Screening attendance after three years of follow-up was 86% in vaccinated women (N=4,897) and 75% in unvaccinated women (N=625,804). The crude HR of screening attendance in vaccinated vs. unvaccinated women was 1.31 (95% CI 1.27-1.35) in the first screening round. Adjustment for education and income reduced but did not erase this difference (HRadj=1.09, 95% CI 1.05-1.13). In the second screening round, attendance was likewise higher in HPV-vaccinated women (crude HR=1.26, 95% CI 1.21-1.32; HRadj=1.15, 95% CI 1.10-1.20).
CONCLUSIONS: HPV-vaccination is so far associated with equal or higher attendance to cervical screening in Sweden in a cohort of opportunistically vaccinated young women. Most but not all of the difference in attendance was explained by socioeconomic differences between vaccinated and unvaccinated women. HPV vaccine effectiveness studies should consider screening attendance of HPV-vaccinated women when assessing incidence of screen-detected cervical lesions.
Access and Attitudes to HPV Vaccination amongst Hard-To-Reach Populations in Kenya.
PLoS One. 2015; 10(6):e0123701 [PubMed] Free Access to Full Article Related Publications
METHODS: Stakeholder interviews with Ministry of Health staff explored barriers to and support for the uptake of HPV vaccination. A situation assessment was conducted to assess community services in Maasai nomadic pastoralist communities in Kajiado County and in Korogocho informal settlement in Nairobi city, followed by focus group discussions (n=14) and semi-structured interviews (n=28) with health workers, parents, youth, and community and religious leaders. These covered marriage, knowledge of cervical cancer and HPV, factors that might inhibit or support HPV vaccine uptake and intention to accept HPV vaccine if a programme was in place.
RESULTS: Reported challenges to an HPV vaccination programme included school absenteeism and drop-out, early age of sex and marriage, lack of parental support, population mobility and distance from services. Despite little prior knowledge of cervical cancer and HPV, communities were interested in receiving HPV vaccination. Adequate social mobilisation and school-based vaccination, supplemented by out-reach activities, were considered important facilitating factors to achieve high coverage. There was some support for a campaign approach to vaccine delivery.
CONCLUSIONS: Given the high level of support for a vaccine against cervical cancer and the experience of reaching pastoralist and slum-dwellers for other immunizations, implementing an HPV vaccine programme should be feasible in such hard-to-reach communities. This may require additional delivery strategies in addition to the standard school-based delivery, with vaccine offered at multiple venues, potentially through a campaign approach.
Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study.
Int J Cancer. 2015; 137(12):2858-68 [PubMed] Free Access to Full Article Related Publications
Cost-effectiveness analysis of introducing universal human papillomavirus vaccination of girls aged 11 years into the National Immunization Program in Brazil.
Vaccine. 2015; 33 Suppl 1:A135-42 [PubMed] Related Publications
METHODS: The Excel-based CERVIVAC decision support model was used to compare two strategies: (1) status quo (with current screening program) and (2) vaccination of a cohort of 11-year-old girls. National parameters for the epidemiology and costs of cervical cancer were estimated in depth. The estimates were based on data from the health information systems of the public health system, the PNAD 2008 national household survey, and relevant scientific literature on Brazil. Costs are expressed in 2008 United States dollars (US$), and a 5% discount rate is applied to both future costs and future health benefits.
RESULTS: Introducing the HPV vaccine would reduce the burden of disease. The model estimated there would be 229 deaths avoided and 6677 disability-adjusted life years (DALYs) averted in the vaccinated cohort. The incremental cost-effectiveness ratios (ICERs) per DALY averted from the perspectives of the government (US$ 7663), health system (US$ 7412), and society (US$ 7298) would be considered cost-effective, according to the parameters adopted by the World Health Organization. In the sensitivity analysis, the ICERs were most sensitive to variations in discount rate, disease burden, vaccine efficacy, and proportion of cervical cancer caused by types 16 and 18. However, universal HPV vaccination remained a cost-effective strategy in most variations of the key estimates.
CONCLUSIONS: Vaccine introduction could contribute additional benefits in controlling cervical cancer, but it requires large investments by the NIP. Among the essential conditions for attaining the expected favorable results are immunization program sustainability, equity in a population perspective, improvement of the screening program, and development of a surveillance system.
Prospective evaluation of p16/Ki-67 dual-stained cytology for managing women with abnormal Papanicolaou cytology: PALMS study results.
Cancer Cytopathol. 2015; 123(6):373-81 [PubMed] Related Publications
METHODS: A total of 575 ASC-US cases and 529 LSIL cases from a cohort of 27,349 women who were prospectively enrolled into the PALMS study in 5 European countries were tested with p16/Ki-67 dual-stained cytology and Hybrid Capture 2 (HC2) HPV testing. Colposcopy-guided biopsy results of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were used as clinical endpoints.
RESULTS: p16/Ki-67 dual-stained cytology demonstrated comparable (ASC-US: 94.4% for dual-stained cytology vs 100% for HC2 testing; P = .317) or lower (LSIL: 85.7% for dual-stained cytology vs 98.4% for HC2 testing; P = .005) sensitivity for CIN2+, but higher levels of specificity compared with HC2 HPV testing in both ASC-US (78.7% vs 60.4%; P<.001) and LSIL (53.3% vs 15.6%; P<.001) cases. Positive predictive values for CIN2+ were substantially higher for dual-stained cytology versus HC2 HPV testing, especially in LSIL, and in ASC-US cases for women aged <30 years.
CONCLUSIONS: The clinical usefulness and efficiency of triaging women with ASC-US or LSIL Papanicolaou cytology results by p16/Ki-67 dual-stained cytology testing has been confirmed in this prospective, pan-European study. The high positive predictive value of dual-stained cytology for the presence of high-grade CIN may help to reduce the number of unnecessary colposcopy referrals.
High-Risk Human Papillomavirus (HPV) Infection and Cervical Cancer Prevention in Britain: Evidence of Differential Uptake of Interventions from a Probability Survey.
Cancer Epidemiol Biomarkers Prev. 2015; 24(5):842-53 [PubMed] Free Access to Full Article Related Publications
METHODS: Natsal-3, a probability sample survey of men and women ages 16 to 74, resident in Britain, interviewed 8,869 women in 2010 to 2012. We explored risk factors for HR-HPV (in urine from 2,569 sexually experienced women ages 16 to 44), nonattendance for cervical screening in the past 5 years, and noncompletion of HPV catch-up vaccination.
RESULTS: HR-HPV was associated with increasing numbers of lifetime partners, younger age, increasing area-level deprivation, and smoking. Screening nonattendance was associated with younger and older age, increasing area-level deprivation (age-adjusted OR 1.91, 95% confidence interval, 1.48-2.47 for living in most vs. least deprived two quintiles), Asian/Asian British ethnicity (1.96, 1.32-2.90), smoking (1.97, 1.57-2.47), and reporting no partner in the past 5 years (2.45, 1.67-3.61 vs. 1 partner) but not with HR-HPV (1.35, 0.79-2.31). Lower uptake of HPV catch-up vaccination was associated with increasing area-level deprivation, non-white ethnicity, smoking, and increasing lifetime partners.
CONCLUSIONS: Socioeconomic markers and smoking were associated with HR-HPV positivity, nonattendance for cervical screening, and noncompletion of catch-up HPV vaccination.
IMPACT: The cervical screening program needs to engage those missing HPV catch-up vaccination to avoid a potential widening of cervical cancer disparities in these cohorts. As some screening nonattenders are at low risk for HR-HPV, tailored approaches may be appropriate to increase screening among higher-risk women.
Efficacy of human papillomavirus 16 and 18 (HPV-16/18) AS04-adjuvanted vaccine against cervical infection and precancer in young women: final event-driven analysis of the randomized, double-blind PATRICIA trial.
Clin Vaccine Immunol. 2015; 22(4):361-73 [PubMed] Free Access to Full Article Related Publications
Do Cell-Cycle Phase-Specific Markers Predict Disease Grade, Stage, and Outcome in Cervical Carcinoma?
Int J Gynecol Cancer. 2015; 25(6):1066-72 [PubMed] Related Publications
METHODS: Pretreatment biopsy material was obtained from 35 patients with cervical cancer (stage IB2-IVA) and 12 normal cervix control cases. Each patient was treated with neoadjuvant chemotherapy followed by chemoradiation. Immunohistochemical staining was performed using a panel of cell cycle phase markers: replication licensing factors: Mcm2 (minichromosome maintenance 2) and geminin, and the standard proliferation marker Ki67 (clone MIB-1).
RESULTS: The expression levels of each cell cycle biomarker were very high in all cases of squamous cell carcinoma of the cervix regardless of grade or stage of disease. In our cohort, all cases displayed an aggressive, so-called actively cycling phenotype. Univariate analysis showed that none of the cell cycle biomarkers predicted grade, stage, or clinical outcome.
CONCLUSIONS: Cell cycle phase-specific markers do not appear to predict disease grade, stage, or outcome in our sample of patients with cervical cancer. This is not surprising, given that the expression of each cell cycle biomarker was very high in all cases.Indeed, all the cases of squamous cell carcinoma of the cervix (n = 28) and all but 1 of the adenocarcinomas (n = 7) in this study displayed an aggressive "actively cycling" phenotype. This predominance of actively cycling tumors is unusual and may reflect the viral etiology underlying the disease. These preliminary findings raise many interesting questions including the prognostic value of disease grade and markers of proliferation in cervical tumors as reliable prognostic indicators. Further work on a larger cohort of patients is warranted.
Human papillomavirus testing 2007-2012: co-testing and triage utilization and impact on subsequent clinical management.
Int J Cancer. 2015; 136(12):2854-63 [PubMed] Free Access to Full Article Related Publications
Comparison of analytical and clinical performances of the digene HC2 HPV DNA assay and the INNO-LiPA HPV genotyping assay for detecting high-risk HPV infection and cervical neoplasia among HIV-positive African women.
J Acquir Immune Defic Syndr. 2015; 68(2):162-8 [PubMed] Related Publications
DESIGN: The tests were compared for agreement in detecting high-risk HPV (hr-HPV) and performance to detect squamous intraepithelial lesions (SIL), by cytology, and cervical intraepithelial neoplasia, by histology, in cervical samples from 1224 women in Burkina Faso (N = 604) and South Africa (N = 620).
RESULTS: When considering the 13 hr-HPV types detected by HC2, 634 (51.8%) and 849 (69.4%) samples were positive by HC2 and INNO-LiPA, respectively. Agreement between assays was 73.9% [adjusted kappa coefficient value, 0.44 (95% confidence interval: 0.43 to 0.53)]. Agreement improved with analysis restricted to women with high-grade cervical lesions [adjusted kappa coefficient value, 0.83 (95% confidence interval: 0.74 to 0.91)]. The prevalence of hr-HPV, as determined by HC2 and INNO-LiPA, was 34.5% and 54.5%, respectively, in samples with normal cytology, 48.0% and 68.0%, respectively, in samples with atypical squamous cells of undetermined significance, 51.8% and 75.2%, respectively, in samples with low-grade SIL, and 86.3% and 89.8%, respectively, in samples with high-grade SIL/atypical squamous cells that cannot exclude HSIL. Sensitivity, specificity, positive, and negative predictive values for the diagnosis of histological high-grade lesions (CIN2+) were 88.8%, 55.2%, 24.7% and 96.7%, and 92.5%, 35.1%, 19.1% and 96.6% for HC2 and INNO-LiPA, respectively.
CONCLUSIONS: HC2 has lower analytical sensitivity but higher specificity than INNO-LiPA for diagnosing high-grade lesions; the 2 tests presented a comparable clinical sensitivity. HC2 might be suitable for cervical cancer screening in HIV-1-infected African women, but its use in resource-limited settings merits to be further evaluated in comparison with other prevention strategies.
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