Will vaccinated women attend cervical screening? A population based survey of human papillomavirus vaccination and cervical screening among young women in Victoria,Australia

Objectives: To assess human papillomavirus (HPV) vaccination coverage and attitudes to vaccination and Pap screening in young women. Design: Population-based telephone survey. Setting: Victoria, Australia. Participants: 234 women resident in Victoria aged 18–28 years in May 2009. Main outcome measures: Self-reported HPV vaccination uptake, reasons for non-receipt or failure to complete vaccination, knowledge and attitudes about HPV vaccination and Pap screening, and cervical screening intentions. Results: The response rate for eligible households was 62.4%. Half of the women (56%, n = 131) had previously had a Pap test and 74% (age standardised estimate) had received HPV vaccine. Of the vaccinated women, 5% had received one dose only, 18% two doses and 76% had completed the course (1.7% unsure of number of doses). Vaccination uptake was highest in the youngest women (declining from 90% for at least one dose in women aged 18–38.5% in women aged 28; p for trend <0.001). Among women who had heard of the vaccine, 96% knew Pap tests were still needed after it, although 20% thought the vaccine could prevent all cervical cancers and 9% thought the vaccine could treat cervical abnormalities and cancer. Among vaccinated women, 8% of women agreed that having been vaccinated made them less likely to have Pap tests in the future. Conclusions: Self-reported coverage in this sample was higher than that recorded on the national vaccination register. Young women report the message that Pap tests are required after vaccination, but there are gaps in their knowledge about the limitations of the vaccine so it remains to be seen if they actually follow through with having Pap tests. Ongoing monitoring of cervical screening rates will be important as this cohort ages.     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Is the prevalence of Taenia taeniaeformis in Microtus arvalis dependent on population density?

Populations of common voles Microtus arvalis were studied as hosts of the tapeworm Taenia taeniaeformis during a 14-yr survey. They were monitored in spring, summer, and autumn in a pastoral ecosystem in eastern France. A total of 7,574 voles were sampled during 2 multiannual population fluctuations. A third fluctuation was sampled during the increase phase only. Overall prevalence was lowest in summer (0.6%), increased by 3 times in autumn (1.5%) and a further 5 times in spring (7.8%). Analysis of prevalence, based on 7,384 voles, by multiple logistic regression revealed that extrinsic factors such as season and intrinsic factors such as host age and host density have a combined effect. In the longer term, host age and host density were positively associated with prevalence in summer. Host density was strongly associated with autumn prevalence. There was no association between the fluctuation phase and prevalence. The study shows that a long timescale (here a multiannual survey) is necessary to demonstrate the positive effect of host density on the prevalence of this indirectly transmitted parasite. The demonstration of this relationship depends on the rodents being intermediate rather than definitive hosts.     

Management of low‐grade cervical abnormalities detected at screening: which method do women prefer?

Objective:  To establish whether women with low-grade abnormalities detected during screening for cervical cancer prefer to be managed by cytological surveillance or by immediate colposcopy.
Methods:  TOMBOLA (Trial of Management of Borderline and Other Low-grade Abnormal smears) is a randomized controlled trial comparing alternative management strategies following the screen-detection of low-grade cytological abnormalities. At exit, a sample of TOMBOLA women completed a questionnaire eliciting opinions on their management, contingent valuations (CV) of the management methods and preferences. Within-trial quality of life (EQ-5D) data collected for a sample of TOMBOLA women throughout their follow-up enabled the comparison of self-reported health at various time points, by management method.
Results:  Once management had been initiated, self-reported health in the colposcopy arm rose relative to that in the surveillance arm, although the effect was short-term only. For the majority of women, the satisfaction ratings and the CV indicated approval of the management method to which they had been randomized. Of the minority manifesting a preference for the method which they had not experienced, relatively more would have preferred colposcopy than would have preferred surveillance.
Conclusions:  The findings must be interpreted in the light of sample bias with respect to preferences, whereby enthusiasm for colposcopy was probably over-represented amongst trial participants. The study suggests that neither of the management methods is preferred unequivocally; rather, individual women have individual preferences, although many would be indifferent between methods.     

Molecular biology of cancer-associated fibroblasts: Can these cells be targeted in anti-cancer therapy?

It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.     

Is there seasonal periodicity in the prevalence of Helicobacter pylori?

The objective of the present study was to evaluate seasonal periodicity in the prevalence of Helicobacter pylori. A prospective study was performed on 1076 consecutive patients who were investigated in our hospital over a 3-year span because of epigastric complaints. Our findings indicate a significant accumulation of positive Helicobacter pylori tests in October. Gastric acidity, gender, and age did not influence Helicobacter pylori infection significantly. There was no significant correlation between potential seasonal influence on the diagnosis of ulcer disease and the seasonal fluctuation of Helicobacter pylori infection. The seasonality was confirmed by cosinor analysis for the absolute frequencies of H. pylori infections and also for the number of cases positive for H. pylori per number of presenting patients per month. A seasonal concept of a sensitivity threshold for positive Helicobacter pylori testing is introduced, taking into account such factors as immune system, nutrition, and medication status.     

Is the involvement of opinion leaders in the implementation of research findings a feasible strategy?

Background

Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial.

Methods

Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient.

Discussion

If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions.     

Costs and benefits of cervical screening. II. Is it worthwhile reducing the screening interval from 5 to 3 years?

A reduction in screening interval from 5 years to 3 years would greatly increase the cost of the programme, but would save few extra lives. The cost per life saved would be around £250 000 at 1995 prices, or around £8000 per life per year saved. There would in addition be human costs for the women screened. The opportunity cost of reducing the interval may be too great, since it is likely that the Health Service would achieve greater health benefits by investing the funds in other health care activities.     

High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma

This study evaluated the relationship between altered cytoplasmic expression of TGF-β1 in tissues of the vaginal incisional margin and vaginal cancer recurrence in patients with stage Ib-IIa cervical squamous cell carcinoma (CSCC). This paper also discusses the prognostic value of TGF-β1 expression at these locations. We found that TGF-β1 expression in the vaginal margin had a close association with vaginal recurrence of stage Ib-IIa CSCC and was an independent prognostic marker of this disease.     

Molecular characterization of head and neck cancer: how close to personalized targeted therapy?

Molecular targeted therapy in head and neck squamous cell carcinoma (HNSCC) continues to make strides, and holds much promise. Cetuximab remains the sole US FDA-approved molecular targeted therapy available for HNSCC, though several new biologic agents targeting the epidermal growth factor receptor (EGFR) and other pathways are currently in the regulatory approval pipeline. While targeted therapies have the potential to be personalized, their current use in HNSCC is not personalized. This is illustrated for EGFR-targeted drugs, where EGFR as a molecular target has yet to be individualized for HNSCC. Future research needs to identify factors that correlate with response (or lack of one) and the underlying genotype-phenotype relationship that dictates this response. Comprehensive exploration of genetic and epigenetic landscapes in HNSCC is opening new frontiers to further enlighten and mechanistically inform newer as well as existing molecular targets, and to set a course for eventually translating these discoveries into therapies for patients. This opinion offers a snapshot of the evolution of molecular subtyping in HNSCC and its current clinical applicability, as well as new emergent paradigms with implications for controlling this disease in the future.     

Is there a pathology of prevention? the implications of visualizing the invisible in screening programs

The preventive orientation that has been gaining ground in Sweden is indicative of ways in which our society is organized to sustain values like a healthy life, a healthy body, and a healthy society. Search for health dangers and risks shows how medical technology has been integrated with our thinking about health. Preventive language, like all language of medicine, besides describing a pre-existing biological reality, creates in the process its own objects of analysis. This also has an impact and influences how lay people experience their bodies. The study presented focuses on one form of prevention in an attempt to describe how the ambition to secure a healthy society, through the detection of early disease, may have the opposite effect. Medical health-care ambitions in screening for cholesterolaemia will be related to implications for a group of men in whom cholesterol was found to be elevated. The men feel healthy yet are in some sense diseased. This raises the issue of visualizing the invisible in health care and the implications of such a process for the patients concermed.