Cost effectiveness analysis of antenatal HIV screening in United Kingdom

ObjectiveTo assess the cost effectiveness of universal antenatal HIV screening compared with selective screening in the United Kingdom.DesignIncremental cost effectiveness analysis relating additional costs of screening to life years gained. Maternal and paediatric costs and life years were combined.SettingUnited Kingdom.ResultsOn base case assumptions, a new diagnosis of a pregnant woman with HIV results in a gain of 6.392 life years and additional expenditure of £14 833. If decision makers are prepared to pay up to £10 000 for an additional life year, this would imply a net benefit of £49 090 (range £12 300-£59 000), which would be available to detect each additional infected woman in an antenatal screening programme. In London, universal antenatal screening would be cost effective compared with a selective screening under any reasonable assumptions about screening costs. Outside London, universal screening with uptake above 90% would be cost effective with a £0.60 HIV antibody test cost and up to 3.5 minutes for pretest discussion. Cost effectiveness of universal testing is lower if selective testing can achieve high uptake among those at higher risk. A universal strategy with only 50% uptake may not be less cost effective in low prevalence districts and may cost more and be less effective than a well run selective strategy.ConclusionsUniversal screening with pretest discussion should be adopted throughout the United Kingdom as part of routine antenatal care as long as test costs can be kept low and uptake high.

Key messages

• In 1997 only 13% of undiagnosed HIV infection in pregnant women was picked up on antenatal testing, resulting in many preventable paediatric infections
• Assuming NHS willingness to pay £10 000 per life year gained, universal testing would be much more cost effective than selective testing throughout London on any reasonable assumptions on costs, prevalence, and uptake of testing
• Outside London, universal testing would also be cost effective, even allowing 2-4 minutes for pretest discussion, provided that test costs were no more than £0.60 and uptake exceeded 90%
• Low cost tests could be achieved by pooling antenatal sera or centralisation of testing
• Universal testing with uptake of 50% may be less cost effective than a well run selective programme

     

Retrospective audit of different antenatal screening policies for Down's syndrome in eight district general hospitals in one health region

ObjectiveTo compare the effectiveness of different screening policies for the antenatal detection of Down''s syndrome.DesignRetrospective six year survey.SettingMaternity units of eight districts.ParticipantsWomen who completed their pregnancies between 1 January 1994 and 31 December 1999 (155 501 deliveries).Results335 cases of Down''s syndrome were identified, 323 in continuing pregnancies or liveborn children. Of these, 171 were identified antenatally. Seven different screening policies were used, in three principal groups: serum screening offered to all mothers, maternal age with serum screening or nuchal translucency available to limited groups, and maternal age combined with anomaly scans. The districts that used serum screening detected 57%, those using maternal age plus serum or nuchal translucency screening 52%, and those using a maternal age of ⩾35 and anomaly scans detected 54%. The least successful district, which offered amniocentesis only to women aged over 37 years, detected only 31%. If amniocentesis had been offered from 35 years, as in all other districts, the detection rate would have risen to 54%. Across the region 15% (range 12-20%) of pregnant women were 35 years or more at delivery, and 58% (33-69%) of infants with Down''s syndrome were born to women in this age range.ConclusionsCurrent additional serum or nuchal translucency screening techniques for antenatal detection of Down''s syndrome are less advantageous than previously supposed. More pregnant women were aged over 35 than has been presumed in statistical models used in demonstration projects of serum screening and, as a result, the proportion of affected fetuses in this age group is much greater than predicted.

What is already known on this topic

Serum screening for Down''s syndrome has been presumed to be more effective than screening by maternal ageThere have been no controlled studies comparing serum screening with screening by maternal age, and its greater efficacy has been presumed from mathematical modelling, which assumed that only 5% of pregnant women were aged over 35 yearsThe modelling predicted that only 20-30% of cases of Down''s syndrome would arise in women aged over 35 and made no allowance for the effects of routine anomaly scanning

What this study adds

15% of pregnant women were aged over 35 years, more than double the 5-7% presumed in statistical models of screening58% of babies with Down''s syndrome were born to women aged 35 years or moreSerum screening and nuchal scanning did not achieve significantly higher antenatal detection rates of Down''s syndrome than the use of maternal age and routine anomaly scanning     

Knowledge and acceptability of pap smears, self-sampling and HPV vaccination among adult women in Kenya

Objectives

Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.

Methods

Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit.

Results

Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost.

Conclusions

These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.     

Prevalence and correlation of human papillomavirus genotypes with clinical factors in cervical samples from Mexican women

In the last decade, the inclusion of HPV DNA testing in cervical cancer screening has provided one of the best strategies for the prevention and timely detection of HPV. We conducted a high-throughput HPV genotyping study based on MALDI-TOF mass spectrometry to determine the prevalence of 24 HPV genotypes, including oncogenic genotypes, in Mexican women and correlated the results with cytological findings and clinical variables. We likewise identified the risk factors in patients with the HPV infection. Our study included 1000 women from Sonora, Mexico, who participated in cervical cancer screening campaigns and who underwent a Pap smear and HPV DNA test. The results showed that the overall prevalence of HPV was 27.2%, 18.5% with single, and 8.7% multiple infections. The low-risk HPV genotype 6 (8.5%) and oncogenic genotypes 31 (8.1%) and 53 (4.4%) were the most prevalent in the study population. The number of lifetime sexual partners, previous STIs, and age at first intercourse was significantly associated with HPV infection (P ≤ 0.05). Smoking (OR = 1.5609; 95% IC 1.062–2.292) and more than three lifetime sexual partners (OR = 1.609; 95% IC = 1.124–2.303) represented risk factors for HPV infection. Cytological abnormalities were found in 3.4% of the HPV-positive samples. CIN 1–3 occurred in 0.6% of high-risk HPV cases. In general, the prevalence of the HPV genotypes is high in Mexican women with normal cytological findings. This issue highlights the importance of HPV research in seemingly healthy women and could help guide screening strategies for cervical cancer prevention in Mexico.Impact statementWe are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1–3 in women with HR-HPV.     

Cervical screening within HIV care: findings from an HIV-positive cohort in Ukraine

Introduction

HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.

Methods

Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.

Results

Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1^st/2^nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3^rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively).

Conclusions

In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.     

Cervical Screening at Age 50–64 Years and the Risk of Cervical Cancer at Age 65 Years and Older: Population-Based Case Control Study

Background

There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50–64 y and cervical cancer at age 65–83 y.

Methods and Findings

Cases were women (n = 1,341) diagnosed with cervical cancer at age 65–83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50–64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13–0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08–0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20–0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21–0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1–2.7) times higher. In women aged 80–83 y the association was weaker (OR = 0.49, 95% CI 0.28–0.83) than in those aged 65–69 y (OR = 0.12, 95% CI 0.09–0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing.

Conclusions

Women with adequate negative screening at age 50–64 y had one-sixth of the risk of cervical cancer at age 65–83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases. Please see later in the article for the Editors'' Summary     

Prevalence of Human Papillomavirus in 5,072 Consecutive Cervical SurePath Samples Evaluated with the Roche Cobas HPV Real-Time PCR Assay

New commercially available Human Papillomavirus (HPV) assays need to be evaluated in a variety of cervical screening settings. Cobas HPV Test (cobas) is a real-time PCR-based assay allowing for separate detection of HPV genotypes 16 and 18 and a bulk of 12 other high-risk genotypes. The aim of the present study, Horizon, was to assess the prevalence of high-risk HPV infections in an area with a high background risk of cervical cancer, where women aged 23–65 years are targeted for cervical screening. We collected 6,258 consecutive cervical samples from the largest cervical screening laboratory in Denmark serving the whole of Copenhagen. All samples were stored in SurePath media. In total, 5,072 samples were tested with cobas, Hybrid Capture 2 High Risk HPV DNA test (HC2) and liquid-based cytology. Of these, 27% tested positive on cobas. This proportion decreased by age, being 43% in women aged 23–29 years and 10% in women aged 60–65 years. HC2 assay was positive in 20% of samples, and cytology was abnormal (≥ atypical squamous cells of undetermined significance) for 7% samples. When only samples without recent abnormalities were taken into account, 24% tested positive on cobas, 19% on HC2, and 5% had abnormal cytology. The proportion of positive cobas samples was higher than in the ATHENA trial. The age-standardized cobas positivity vs. cytology abnormality was 3.9 in our study and 1.7 in ATHENA. If in Copenhagen the presently used cytology would be replaced by cobas in women above age 30 years, an extra 11% of women would based on historical data be expected to have a positive cobas test without an underlying cervical intraepithelial lesion grade 3 or worse. Countries with a high prevalence of HPV infections should therefore proceed to primary HPV-based cervical screening with caution.     

Evaluation of the Lung Cancer Risks at Which to Screen Ever- and Never-Smokers: Screening Rules Applied to the PLCO and NLST Cohorts

BackgroundLung cancer risks at which individuals should be screened with computed tomography (CT) for lung cancer are undecided. This study''s objectives are to identify a risk threshold for selecting individuals for screening, to compare its efficiency with the U.S. Preventive Services Task Force (USPSTF) criteria for identifying screenees, and to determine whether never-smokers should be screened. Lung cancer risks are compared between smokers aged 55–64 and ≥65–80 y.ConclusionsThe USPSTF criteria for CT screening include some low-risk individuals and exclude some high-risk individuals. Use of the PLCO_m2012 risk ≥0.0151 criterion can improve screening efficiency. Currently, never-smokers should not be screened. Smokers aged ≥65–80 y are a high-risk group who may benefit from screening. Please see later in the article for the Editors'' Summary     

Prevalence and Predictors of Colposcopic-Histopathologically Confirmed Cervical Intraepithelial Neoplasia in HIV-Infected Women in India

Background

Prevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools.

Methodology

Previously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation including standardized diagnostic colposcopy by a gynecologist. Histopathologic confirmation was conducted among consenting women with clinical suspicion of CIN. The prevalence of CIN was evaluated by a composite diagnosis based on colposcopy and histopathology results. Multivariable ordinal logistic regression analysis was conducted to determine independent predictors of increasing severity of CIN.

Results

The median age of the n = 303 enrolled HIV-infected women was 30 years (interquartile range, 27–34). A majority of the participants were widowed or separated (187/303, 61.7%), more than one-third (114/302, 37.7%) were not educated beyond primary school, and nearly two-thirds (196/301, 64.7%) had a family per capita income of <1,000 Indian Rupees (∼US$22) per month. Cervical high-risk HPV-DNA was detected in 41.7% (124/297) of participants. The composite colposcopic-histopathologic diagnoses revealed no evidence of CIN in 220 out of 303 (72.6%) women, CIN1 in 33/303 (10.9%), CIN2 in 31/303 (10.2%), CIN3 in 18/303 (5.9%) and 1 (0.3%) woman was diagnosed with ICC. Thus, over a quarter of the participants [83/303: 27.7% (95% CI: 22.7–33.1)] had ≥CIN1 lesions and a sixth [50/303: 16.5% (95% CI: 12.2–21.9)] had evidence of advanced (≥CIN2) neoplastic disease. The independent predictors of increasing severity of CIN as revealed by a proportional odds model using multivariable ordinal logistic regression included (i) currently receiving antiretroviral therapy [adjusted odds ratios (aOR): 2.24 (1.17, 4.26), p = 0.01] and (ii) presence of cervical high-risk HPV-DNA [aOR: 1.93 (1.13, 3.28), p = 0.02].

Conclusions

HIV-infected women in Pune, India have a substantial burden of cervical precancerous lesions, which may progress to invasive cervical cancer unless appropriately detected and treated. Increased attention should focus on recognizing and addressing this entirely preventable cancer among HIV-infected women, especially in the context of increasing longevity due to antiretroviral therapy.     

Impact of an Educational Intervention on Women's Knowledge and Acceptability of Human Papillomavirus Self-Sampling: A Randomized Controlled Trial in Cameroon

ObjectiveHuman papillomavirus (HPV) self-sampling (Self-HPV) may be used as a primary cervical cancer screening method in a low resource setting. Our aim was to evaluate whether an educational intervention would improve women''s knowledge and confidence in the Self-HPV method.MethodWomen aged between 25 and 65 years old, eligible for cervical cancer screening, were randomly chosen to receive standard information (control group) or standard information followed by educational intervention (interventional group). Standard information included explanations about what the test detects (HPV), the link between HPV and cervical cancer and how to perform HPV self-sampling. The educational intervention consisted of a culturally tailored video about HPV, cervical cancer, Self-HPV and its relevancy as a screening test. All participants completed a questionnaire that assessed sociodemographic data, women''s knowledge about cervical cancer and acceptability of Self-HPV.ResultsA total of 302 women were enrolled in 4 health care centers in Yaoundé and the surrounding countryside. 301 women (149 in the “control group” and 152 in the “intervention group”) completed the full process and were included into the analysis. Participants who received the educational intervention had a significantly higher knowledge about HPV and cervical cancer than the control group (p<0.05), but no significant difference on Self-HPV acceptability and confidence in the method was noticed between the two groups.ConclusionEducational intervention promotes an increase in knowledge about HPV and cervical cancer. Further investigation should be conducted to determine if this intervention can be sustained beyond the short term and influences screening behavior.

Trials Registration

International Standard Randomised Controlled Trial Number (ISRCTN) Register ISRCTN78123709     

Trends in breast cancer mortality in Sweden before and after implementation of mammography screening

Background

Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s.

Objective

We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start.

Results

Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age.

Discussion

Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.     

Cervical Cancer Screening Service Uptake and Associated Factors among Age Eligible Women in Mekelle Zone,Northern Ethiopia, 2015: A Community Based Study Using Health Belief Model

Introduction

Cervical cancer is the third most common cancer among women worldwide, with about 500,000 new patients diagnosed and over 250,000 deaths every year. Cervical cancer screening offers protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality. But there is very low participation rate in screening for cervical cancer among low and middle-income countries.

Objective

This study aimed to determine cervical cancer screening service uptake and its associated factor among age eligible women in Mekelle zone, northern Ethiopia, 2015.

Methods

A community based cross-sectional study was conducted in Mekelle zone among age eligible women from February to June 2015. Systematic sampling technique was used to select 1286 women in to the study. A pre-tested structured questionnaire was used to collect relevant data. Data was entered and cleaned using EPINFO and analyzed using SPSS version 20 software package. Bivariate and Multivariate logistic regression was performed to assess association between dependent and independent variables with 95% CI and p-value less than 0.05 was set for association.

Results

The study revealed that among 1186 age eligible women, only 235(19.8%) have been screened for cervical cancer. Age (AOR = 1.799, 95%CI = 1.182–2.739), history of multiple sexual partners (AOR = 1.635, 95%CI = 1.094–2.443), history of sexually transmitted disease (AOR = 1.635,95%CI = 1.094–2.443), HIV sero status (AOR = 5.614, 95%CI = 2.595–12.144), perceived susceptibility to cervical cancer (AOR = 2.225, 95%CI = 1.308–3.783), perceived barriers to premalignant cervical lesions screening (AOR = 2.256, 95%CI = 1.447–3.517) and knowledge on cervical cancer and screening (AOR = 2.355, 95%CI = 1.155–4.802) were significant predictors of cervical cancer screening service uptake.

Conclusion

Magnitude of cervical cancer screening service uptake among age eligible women is still unacceptably low. Age of the women, history of multiple sexual partners and sexually transmitted disease, HIV sero-positivity, Knowledge, Perceived susceptibility and Perceived Barrier were important predictors of cervical cancer screening service uptake.     

Acceptability and Correlates of Primary and Secondary Prevention of Cervical Cancer among Medical Students in Southwest China: Implications for Cancer Education

Objectives

To understand knowledge about, and acceptability of, cervical cancer screening and HPV vaccines among medical students; and to explore potential factors that influence their acceptability in China.

Methods

We conducted a survey among medical students at six universities across southwest China using a 58-item questionnaire regarding knowledge and perceptions of HPV, cervical cancer, and HPV vaccines.

Results

We surveyed 1878 medical students with a mean age of 20.8 years (standard deviation: 1.3 years). Of these, 48.8% and 80.1% believed cervical cancer can be prevented by HPV vaccines and screening respectively, while 60.2% and 71.2% would like to receive or recommend HPV vaccines and screening. 35.4% thought HPV vaccines ought to be given to adolescents aged 13–18 years. 32% stated that women should start to undergo screening from the age of 25. 49.2% felt that women should receive screening every year. Concern about side effects (38.3% and 39.8%), and inadequate information (42.4% and 35.0%) were the most cited barriers to receiving or recommending HPV vaccination and cervical cancer screening. Females were more likely to accept HPV vaccines (OR, 1.86; 95% CI: 1.47–2.35) or cervical cancer screening (OR, 3.69; 95% CI: 2.88–4.74). Students with a higher level of related knowledge were much more willing to receive or recommend vaccines (P<0.001) or screening (P<0.001). Students who showed negative or uncertain attitudes towards premarital sex were less likely to accept either HPV vaccines (OR, 0.67; 95% CI: 0.47–0.96), or screening (OR, 0.68; 0.47–0.10). Non-clinical students showed lower acceptability of cervical screening compared to students in clinical medicine (OR, 0.74; 95% CI: 0.56–0.96).

Conclusions

The acceptability of HPV vaccines and cervical cancer screening is relatively low among medical students in southwest China. Measures should be taken to improve knowledge about cervical cancer and awareness of HPV vaccines and screening among medical students at university.     

Women's understanding of a "normal smear test result": experimental questionnaire based study

ObjectivesTo describe women''s understanding of a negative smear test result when presented using the term “normal smear result,” as required by the NHS cervical screening programme, and to evaluate the impact on understanding of different ways of presenting the residual risk inherent in such a result.DesignExperimental questionnaire based study.InterventionsParticipants were asked to imagine that they had received a normal smear result. The meaning of this result was then presented using different combinations of three different expressions of residual risk of having or developing cervical cancer over the next five years: a verbal probability of absolute risk (low risk), a numerical probability of absolute risk (1 in 5000), or a numerical probability of risk relative to an unscreened woman (five times lower).Participants1027 women aged 20 to 64.ResultsWhen informed only that their smear result was normal, 52% (80 of 153 women) of participants correctly understood that this entailed a residual risk of cervical cancer, compared with 70% (107 of 152) given the additional sentence explaining the meaning of a normal smear result using a verbal probability of absolute risk (difference 18%; 95% confidence interval 7% to 29%). Additionally, explaining the results using a numerical probability of absolute or relative risk did not increase the proportion who correctly understood that there was a residual risk of cervical cancer.ConclusionsNHS policy for reporting normal smears needs to change to make it a definite requirement that the reporting of a “normal smear result” is accompanied by a sentence stating that this means a low risk for having or developing cervical cancer in the next five years.     

Evaluation of a structured test and a parent led method for screening for speech and language problems: prospective population based study

ObjectiveTo evaluate two methods for identifying speech and language problems in preschool children.DesignProspective population based study.SettingInner London.ResultsReference assessments and usable scores were obtained for 458 (97%) of the 474 children screened. 98 (21%) children had severe language problems and 131 (29%) needed therapy. The sensitivity and specificity for the structured screening test were 66% (95% confidence interval 53% to 76%) and 89% (85% to 93%) respectively for severe language problems and 54% (43% to 65%) and 90% (85% to 93%) for those needing therapy. The sensitivity and specificity for referral by the parent led method were 56% (40% to 71%) and 85% (78% to 90%) for severe language problems and 58% (44% to 71%) and 90% (83% to 94%) for those needing speech and language therapy.ConclusionsBoth approaches failed to detect a substantial proportion of children with severe language problems and led to over-referral for diagnostic assessments. Screening is likely to be an ineffective approach to the management of speech and language problems in preschool children in this population.

What is already known on this topic

Moderate to severe language difficulties in young children are predictive of long term problems affecting learning, school achievement, and behaviourFormal screening tests are widely used, but relying on parents'' observations and health professionals'' clinical judgment may be more effective in identifying children needing therapy

What this study adds

A commonly used screening test and an approach based on parents'' observations and health visitors'' judgment fail to identify a substantial proportion of children with serious language problems and lead to the over-referral of children without serious difficulties     

Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study

ObjectivesTo determine the prevalence of left ventricular systolic dysfunction, and of heart failure due to different causes, in patients with risk factors for these conditions.DesignEpidemiological study, including detailed clinical assessment, electrocardiography, and echocardiography.Setting16 English general practices, representative for socioeconomic status and practice type.Participants1062 patients (66% response rate) with previous myocardial infarction, angina, hypertension, or diabetes.ResultsDefinite systolic dysfunction (ejection fraction <40%) was found in 54/244 (22.1%, 95% confidence interval 17.1% to 27.9%) patients with previous myocardial infarction, 26/321 (8.1%, 5.4% to 11.6%) with angina, 7/388 (1.8%, 0.7% to 3.7%) with hypertension, and 12/208 (5.8%, 3.0% to 9.9%) with diabetes. In each group, approximately half of these patients had symptoms of dyspnoea, and therefore had heart failure. Overall rates of heart failure, defined as symptoms of dyspnoea plus objective evidence of cardiac dysfunction (systolic dysfunction, atrial fibrillation, or clinically significant valve disease) were 16.0% (11.6% to 21.2%) in patients with previous myocardial infarction, 8.4% (5.6% to 12.0%) in those with angina, 2.8% (1.4% to 5.0%) in those with hypertension, and 7.7% (4.5% to 12.2%) in those with diabetes.ConclusionMany people with ischaemic heart disease or diabetes have systolic dysfunction or heart failure. The data support the need for trials of targeted echocardiographic screening, in view of the major benefits of modern treatment. In contrast, patients with uncomplicated hypertension have similar rates to the general population.

What is already known on this topic

The prognosis and symptoms of patients with left ventricular systolic dysfunction and heart failure can be greatly improved by modern treatmentsMany patients with heart failure do not have an assessment of left ventricular function, resulting in undertreatment of the condition

What this study adds

Patients with a history of ischaemic heart disease (especially those with previous myocardial infarction) or diabetes commonly have left ventricular systolic dysfunctionThese patients would be candidates for a targeted echocardiographic screening programmeIn contrast, the yield from screening patients with uncomplicated hypertension would be low     

Cervical cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) in four US-Affiliated Pacific Islands between 2007 and 2015

BackgroundCervical cancer incidence in the US-Affiliated Pacific Islands (USAPIs) is double that of the US mainland. American Samoa, Commonwealth of Northern Mariana Islands (CNMI), Guam and the Republic of Palau receive funding from the Centers for Disease Control (CDC) National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to implement cervical cancer screening to low-income, uninsured or under insured women. The USAPI grantees report data on screening and follow-up activities to the CDC.Materials and methodsWe examined cervical cancer screening and follow-up data from the NBCCEDP programs in the four USAPIs from 2007 to 2015. We summarized screening done by Papanicolaou (Pap) and oncogenic human papillomavirus (HPV) tests, follow-up and diagnostic tests provided, and histology results observed.ResultsA total of 22,249 Pap tests were conducted in 14,206 women in the four USAPIs programs from 2007–2015. The overall percentages of abnormal Pap results (low-grade squamous intraepithelial lesions or worse) was 2.4% for first program screens and 1.8% for subsequent program screens. Histology results showed a high proportion of cervical intraepithelial neoplasia grade 2 or worse (57%) among women with precancers and cancers. Roughly one-third (32%) of Pap test results warranting follow-up had no data recorded on diagnostic tests or follow-up done.ConclusionThis is the first report of cervical cancer screening and outcomes of women served in the USAPI through the NBCCEDP with similar results for abnormal Pap tests, but higher proportion of precancers and cancers, when compared to national NBCCEDP data. The USAPI face significant challenges in implementing cervical cancer screening, particularly in providing and recording data on diagnostic tests and follow-up. The screening programs in the USAPI should further examine specific barriers to follow-up of women with abnormal Pap results and possible solutions to address them.     

Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent

BackgroundObservational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors.MethodsWe applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases  =  46,325, controls  =  42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively.ResultsIn the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]  =  0.65 per 5 kg/m² increase, 95% confidence interval [CI]: 0.56–0.75, p = 3.32 × 10⁻¹⁰). The associations were similar for both premenopausal (OR   =   0.44, 95% CI:0.31–0.62, p  =  9.91 × 10⁻⁸) and postmenopausal breast cancer (OR  =  0.57, 95% CI: 0.46–0.71, p  =  1.88 × 10⁻⁸). This association was replicated in the data from the DRIVE consortium (OR  =  0.72, 95% CI: 0.60–0.84, p   =   1.64 × 10⁻⁷). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk.ConclusionsBMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.     

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

ObjectivesTo assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia.DesignCost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated.ParticipantsSimulated population aged 16-54 years in England and Wales.InterventionsIdentification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients.ResultsTracing of family members was the most cost effective strategy (£3097 (€5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation).ConclusionsScreening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population.

What is already known on this topic

In the United Kingdom there are an estimated 110 000 men and women with familial hypercholesterolaemia, only a small percentage of whom have been identified to dateWithout identification and treatment, over half of these people will have a fatal or non-fatal coronary heart disease event by the age of 50 (men) or 60 (women)Effective treatment of high cholesterol concentrations reduces total and coronary heart disease mortalityNo recommended screening strategy currently exists in the United Kingdom for familial hypercholesterolaemia

What this study adds

Computer modelling has shown that the earlier familial hypercholesterolaemia is diagnosed the more cost effective the screening strategy becomesIdentifying relatives of people with familial hypercholesterolaemia is the most cost effective screening option for all age groupsAs technology improves and the cost of statins falls all strategies will become more cost effective