False-positive Screening Test Results Research Articles

Estimating the lifetime risk of a false positive screening test result.

False positive results in screening tests have potentially severe psychological, medical, and financial consequences for the recipient. However, there have been few efforts to quantify how the risk of a false positive accumulates over time. We seek to fill this gap by estimating the probability that an individual who adheres to the U.S. Preventive Services Task Force (USPSTF) screening guidelines will receive at least one false positive in a lifetime. To do so, we assembled a data set of 116 studies cited by the USPSTF that report the number of true positives, false negatives, true negatives, and false positives for the primary screening procedure for one of five cancers or six sexually transmitted diseases. We use these data to estimate the probability that an individual in one of 14 demographic subpopulations will receive at least one false positive for one of these eleven diseases in a lifetime. We specify a suitable statistical model to account for the hierarchical structure of the data, and we use the parametric bootstrap to quantify the uncertainty surrounding our estimates. The estimated probability of receiving at least one false positive in a lifetime is 85.5% (±0.9%) and 38.9% (±3.6%) for baseline groups of women and men, respectively. It is higher for subpopulations recommended to screen more frequently than the baseline, including more vulnerable groups such as pregnant women and men who have sex with men. Since screening technology is imperfect, false positives remain inevitable. The high lifetime risk of a false positive reveals the importance of educating patients about this phenomenon.

How do women experience a false-positive test result from breast screening? A systematic review and thematic synthesis of qualitative studies

BackgroundThis is the first review to identify, appraise and synthesise women’s experiences of having a false-positive breast screening test result.MethodsWe systematically searched eight databases for qualitative research reporting women’s experiences of receiving a false-positive screening test result. Two reviewers independently screened articles. Eight papers reporting seven studies were included. Study quality was appraised. Data were thematically synthesised.ResultsWomen passively attended screening in order to prove their perceived good health. Consequently, being recalled was unexpected, shocking and disempowering: women felt without options. They endured great uncertainty and stress and sought clarity about their health (e.g. by scrutinising the wording of recall letters and conversations with healthcare professionals). Their result was accompanied by relief and welcome feelings of certainty about their health, but some received unclear explanations of their result, contributing to lasting breast cancer-related worry and an ongoing need for further reassurance.ConclusionThe organisation of breast screening programmes may constrain choice for women: they became passive recipients. The way healthcare professionals verbally communicate results to women may contribute to lasting breast cancer-related worry. Women need more reassurance, emotional support and answers to their questions before and during screening assessment, and after receiving their result.

Demographic, clinical, dispositional, and social-environmental characteristics associated with psychological response to a false positive ovarian cancer screening test: a longitudinal study.

Cancer screening can facilitate early detection that improves survival, but also can identify an abnormal finding that is not malignant and deemed benign. While such false positive (FP) results can impact a variety of psychological outcomes, little is known about demographic, clinical, dispositional, and social-environmental characteristics associated with psychological outcomes after a FP result. Women participating in an ovarian cancer (OC) screening program and experiencing a FP screening test result (n=375) completed assessments at baseline and 4-months. Results indicated greater social constraint and less education were linked to greater OC-specific distress at both assessments. Short-term predictors included less optimism and no previous abnormal test, while longer-term predictors were fewer previous screens and the interaction between OC family history and monitoring coping style. Younger age, less education, less optimism, greater social constraint, and family history of OC were associated with greater perceptions of OC risk. Brief interventions prior to screening may minimize the negative impact of a false positive result and not interfere with compliant participation in screening programs.

Iodine-containing disinfectants in preparation for caesarean section: impact on thyroid profile in cord blood

BackgroundIodine-containing disinfectants are widely used for skin preparation before caesarean section. Current evidence suggests that maternal exposure to these disinfectants results in thyroid dysfunction in the newborns, but its extent...

The influence of sex, gestational age, birth weight, blood transfusion, and timing of the heel prick on the pancreatitis‐associated protein concentration in newborn screening for cystic fibrosis

Pancreatitis-associated protein (PAP) is currently discussed as a marker in newborn screening (NBS) for cystic fibrosis (CF). However, it is not known if PAP concentrations are influenced by sex, gestational age, birth weight, blood transfusion or time of collection and what this would mean for NBS for CF. In 2008 all newborns in part of the Netherlands were screened for CF by an IRT/PAP protocol. PAP concentration was determined by the MucoPAP ELISA (DynaBio), which was modified to a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) method following a protocol of PerkinElmer. In healthy newborns, the median PAP concentration was 0.5 μg/l (Interquartile range (IQR 0.3-0.8) whereas this was 3.2 μg/l (IQR 2.0-12.5) in CF infants. PAP concentrations were lower in premature infants 0.94 and 0.91 times for 25 to 31 + 6 weeks GA and 32 to 36 + 6 weeks respectively. A higher PAP concentration was observed in low-birth-weight infants (<2500 gram)(p = 0.001), per 100 gram birth weight gained the PAP concentration decreased with 0.1 %. PAP levels were higher after a blood transfusion, the 95th percentile increased from 1.3 to 3.6 μg/l leading to a higher false-positive rate. The PAP concentration increased when newborn screening was performed more than 168 hours (day 7) after birth (β = 1.63), the 95th percentile increased from 1.3-1.6 μg/l to 4.0 μg/l after 168 hours (72,874 newborns were screened). Sex, birth weight, and gestational age lead to small differences in PAP concentrations without consequences for the screening algorithm. However, blood transfusion as well as performance of the heel prick after 168 hours (7 days) lead to clinically significant higher PAP levels and to a higher risk on a false-positive screening test result.

The Impact of Analytical Sensitivity on Screening Algorithms for Syphilis

To the Editor: Assays for syphilis serology can be broadly divided into 2 categories; treponemal tests that detect antibodies against the infectious agent Treponema pallidum , and nontreponemal tests that measure antibodies against nonspecific antigens, such as cardiolipin. Historically, syphilis diagnosis has used a nontreponemal assay such as rapid plasma reagin (RPR) for screening, followed by a treponemal assay to confirm syphilis infection in screen-positive patients. With the increased availability of automated assays for treponemal antibodies, however, many laboratories have shifted to a “treponemal-first” algorithm for syphilis testing. The merits of the 2 approaches have been debated in the literature in terms of clinical utility and cost-effectiveness (1, 2). The main difference between the 2 approaches is the identification of treponemal-positive,RPR-negative patients when a treponemal-first algorithm is used (3). Discriminating between latent syphilis infection and a false-positive screening test result can be challenging for patients without a clear history of prior disease. In such cases, the CDC has recommended retesting samples with a second treponemal assay to confirm the presence of antitreponemal antibodies (4). For such an algorithm to be valid, the analytical sensitivity of the confirmatory treponemal …

Effect of Screening on Ovarian Cancer Mortality

Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality. To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Screening for Sudden Cardiac Death in the Young

Sudden cardiac death (SCD) in the young (SCDY) has a devastating impact on families, care providers, and the community and attracts significant public and media attention. Sudden cardiac death is defined as an abrupt and unexpected death due to a cardiovascular cause, typically occurring 1 hour from the onset of symptoms. Depending on the source, “young” is variably defined as those less than 25, 30, 35, or 40 years of age. Estimates of the incidence of SCDY (not including infants) vary broadly from 0.6 to 6.2 per 100 000 persons. 1–3 Sudden infant death syndrome (SIDS) may be related to SCD in some infants. Sudden infant death syndrome is defined as the sudden death of an infant 1 year of age that cannot be explained after a thorough investigation is conducted, including an autopsy, death scene evaluation, and review of the clinical history. The incidence of SIDS ranges from 50 to 100 in 100 000,4 and emerging data suggest that as many as 10% to 15% of SIDS deaths are associated with functional cardiac ion channelopathy gene variants.5 The most common diagnoses that increase risk for SCDY include hypertrophic cardiomyopathy (HCM), coronary artery anomalies of wrong sinus origin, myocarditis, arrhythmogenic right ventricular cardiomyopathy, and ion channelopathies.6 The latter category includes hereditary diseases such as the congenital long-QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome, among other less common channelopathies. These diseases are typically undetected before the SCD event. Estimated prevalence rates of these conditions range from 1 per 500 persons for HCM to 1 per 2500 for the LQTS. SCD related to these diagnoses has been documented in infancy and during competitive athletics. In addition, prescription stimulant use for treatment of attention deficit hyperactivity disorder (ADHD) has been postulated to be a trigger for SCD.7,8 Sudden cardiac death in the young is a critical public health issue. A young life cut short represents a devastating event for families, and is associated with many lost productive years. There is significant dissonance among experts in the field about the best approach to prevent SCDY in the United States. Some experts support the implementation of largescale cardiovascular screening programs in infants, in athletes, or in all children to identify at-risk individuals in an effort to prevent SCDY. Cardiovascular screening for SCDY typically involves the addition of an ECG to the current standard of care of history and physical examination. Echocardiography and genetic testing represent alternative or additional screening modalities. Observational data from the Veneto region of Italy suggest that ECG screening can successfully identify at-risk cardiovascular diseases and dramatically reduce the incidence of SCD in competitive athletes.9,10 Proponents of ECG screening in the United States suggest that it can be effective, feasible, and cost-effective. 11 Critics of ECG screening cite a lack of evidence to support its effectiveness or feasibility in the United States; lack of clinical accuracy; cost implications; and the potential clinical, financial, and emotional consequences of falsepositive screening test results. 12 Cost estimates for a national ECG screening program in the United States for

Receipt of a False Positive Test Result During Routine Screening for Ovarian Cancer: A Teachable Moment?

The term "teachable moment" (TM) has been used to describe a life transition or event which motivates an individual to change a behavior or presents an opportunity to intervene to prompt behavior change. We examined whether receipt of a false positive ovarian cancer (OC) screening result may represent a TM. 403 women participating in an OC screening program completed questionnaires assessing demographic, clinical, behavioral, and psychosocial information. The TM was operationalized as expressed interest in receiving health-related information. We hypothesized that among women receiving a false positive screening test result, those women who had experienced greater personal perceived risk for OC as well as distress would be more interested in receiving health-related information than women receiving a normal result. Analyses revealed that women receiving a false positive screening result were less interested in receiving health-related information than women receiving a normal screening result. For women receiving a false positive result, expressed interest in receipt of health-related information was only modestly related to distress and related even less to perceptions of OC risk. Our data do not support viewing a false positive OC screening result as a TM. Potential explanations for the current findings as well as recommendations for future research investigating the TM are discussed.

Potential effects of decreased cervical cancer screening participation after HPV vaccination: An example from the U.S.

A concern with widespread implementation of HPV vaccination programs is that women may mistakenly decide that they do not need to be screened any longer, and thus be less likely to participate in cervical cancer screening, because they view themselves to be at low-risk of developing cervical cancer. We hypothesized that non-participation in screening among vaccinated young women in the 5 years following vaccination may result in missed CIN 2–3 cases that could progress to cancer. For instance, if 50% fewer women 26–30 years old, who were vaccinated, participate in screening in the United States over a 5 year time horizon, there would be approximately 4 women (per 1000) with missed CIN 2–3. On the other hand, non-participation will reduce the number of false-positive screening test results, as non-participation would avoid approximately 27 false-positive test results, with a decrease in follow-up procedures and costs. These results highlight the importance of educating women to ensure continued screening, as well as the need to consider new approaches to screening in the era of vaccination.

Serum PAPP-A Levels at 10–14 Weeks of Gestation Are Altered in Women After Assisted Conception

The most sensitive and specific first-trimester Down syndrome screening test employs a combination of maternal age, nuchal translucency (NT) thickness, fβhCG, and PAPP-A. First trimester NT measurements do not differ significantly between pregnancies resulting from assisted reproductive technology (ART) and those resulting from spontaneous conception, but maternal blood levels of free beta human chorionic gonadotropin (fβhCG) are higher following in vitro fertilization-embryo transfer (IVF-ET), and levels of pregnancy-associated plasma protein-A (PAPP-A) are lower. Whether or not this results in a higher rate of false positive screening test results is controversial. The investigators compared the screen-positive rates of the first trimester Down syndrome screening test in women with singleton ART pregnancies to those of women whose pregnancies resulted from spontaneous conception. Participants included 130 women who were pregnant after IVF-ET (group 1); 54 who conceived after intracytoplasmic sperm injection (ISCI; group 2); and 914 control women who conceived spontaneously. Fetal NT thickness was estimated at 10–14 weeks’ gestation. Women who conceived via ICSI were 2.8 times as more likely to be screen positive than control women. Although ovarian stimulation in group 1 and group 2 women was associated with significantly lower PAPP-A levels than were present in the control group, women who conceived via IVF-ET were not more likely to be screen positive than control women. Levels of PAPP-A declined significantly as the number of retrieved oocytes or transferred embryos increased, but the levels of other markers were not affected. When a single embryo was transferred, or when ART conception occurred without ovarian stimulation, marker levels were similar to those following spontaneous conception. Although ICSI appears to be associated with a higher rate of false positive first trimester screening test results than that in spontaneously conceived pregnancies, women who conceive by other ART methods are not at increased risk.

Universal newborn screening and adverse medical outcomes: A historical note

Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results.

Early lung cancer action project: initial findings on repeat screenings.

The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. A cohort of 1000 high-risk individuals was recruited for baseline and annual repeat CT screening. At last follow-up, a total of 1184 annual repeat screenings had been performed. A positive result from the screening test was defined as newly detected, one to six noncalcified pulmonary nodules with interim growth. The diagnostic workup of the individuals was guided by recommendations supplied by the ELCAP investigators to the collaborating clinicians. Of the 1184 repeat CT screenings, the test result was positive in 30 (2.5%). In 2 of these 30 cases, the individual died (of an unrelated cause) before diagnostic workup and the nodule(s) resolved in another 12 individuals. In the remaining 16 individuals, the absence of further growth was documented by repeat CT in 8 individuals and further growth was documented in the remaining 8 individuals. All eight individuals with further nodular growth underwent biopsy and malignancy was diagnosed in seven. Six of these seven malignancies were nonsmall cell carcinomas (five of which were Stage IA and one of which was Stage IIIA) and the one small cell carcinoma was found to be of limited stage. The median size dimension of these malignancies was 8 mm. In another two subjects, symptoms prompted the interim diagnosis of lung carcinoma. Neither of these malignancies was nodule-associated but rather were endobronchial; one was a Stage IIB nonsmall cell carcinoma and the other was a small cell carcinoma of limited stage. False-positive screening test results are uncommon and usually manageable without biopsy; compared with no screening, such screenings permit diagnosis at substantially earlier and thus more curable stages. Annual repetition of CT screening is sufficient to minimize symptom-prompted interim diagnoses of nodule-associated malignancies.

Concordance of Tests to Detect Antibodies to Hepatitis C Virus

A large variety of new assays are available to test for antibodies to hepatitis C virus. We investigated the concordance of two FDA-licensed screening assays and determined their specificities in relation to two supplemental tests, Abbott’s neutralization assay and Ortho’s second generation RIBA-2. Of 573 serum samples from individuals at high risk for sexually transmitted diseases, 81 (14.1%) were repeatedly reactive by both screening tests and produced positive results by both supplemental assays, while 480 (83.8%) samples were nonreactive. Ten of the positive samples were reactive by the RIBA-2 assay to at least two antigens other than cl00-3, and were neutralized (88% to 100%) by Abbott’s supplemental assay. Twelve samples produced discrepant results, including one false-negative and 10 false-positive screening test results.