Bruce Kessel

Contrary to the practice during previous epidemics, with COVID-19 health authorities have treated a single positive result from a PCR-based test as confirmation of infection, irrespective of signs, symptoms and exposure. This is based on a widespread belief that positive results in these tests are highly reliable. However, evidence from external quality assessments and real-world data indicate enough a high enough false positive rate to make positive results highly unreliable over a broad range of scenarios. This has clinical and case management implications, and affects an array of epidemiological statistics, including the asymptomatic ratio, prevalence, and hospitalization and death rates, as well as epidemiologic models. Steps should be taken to raise awareness of false positives and reduce their frequency. The most important immediate action is to check positive results with additional tests, at least when prevalence is low. Key messages: The high specificities (usually 100%) reported in PCR-based tests for SARS-CoV-2 infection do not represent the real-world use of these tests, where contamination and human error produce significant rates of false positives. Widespread lack of awareness of the real-world false positive rates affects an array of clinical, case management and health policy decisions. Similarly, health authorities’ guidance on interpreting test results is often wrong. Steps should be taken immediately to reduce the frequency and impacts of false positive results, including checking positive results with additional tests at least when prevalence is low.

Lai T, et al. J Gynecol Oncol. 2016 Apr;27(4):e41. https://doi.org/10.3802/jgo.2016.27.e41

Terada KY, et al. J Gynecol Oncol. 2015 Dec;27(3):e25. http://dx.doi.org/10.3802/jgo.2016.27.e25

Many simple ovarian cysts are being detected in postmenopausal women with increasing use of transvaginal ultrasound. In the past, aggressive surgical approaches were used for management of simple cysts. Some investigators recommend careful monitoring and others question if simple cysts should be monitored at all. This observational cohort study investigated the occurrence and natural history of simple ovarian cysts within a cohort of 15,535 mostly postmenopausal women in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Four annual serial transvaginal ultrasound screening examinations were performed. Simple ovarian cysts were detected in 14% (2217/15,735) of the cohort during the first fully visualized screen of the ovaries (incident cyst). The incidence of new simple cysts during the first year was 8%, and remained relatively constant throughout the course of the trial. At the second ultrasound screen 1 year later, 54% of the ovaries with 1 simple cyst at the first screen retained 1 simple cyst and 32% had no cyst. The presence of simple cysts was not associated with increased risk of subsequent invasive ovarian cancer. These findings show that the occurrence of simple ovarian cysts in postmenopausal women is a common incidental finding on ultrasound, and support recent recommendations that such cysts should be followed in older women without intervention.

OBJECTIVE: To test whether annual screening with transvaginal ultrasonography and CA 125 reduces ovarian cancer mortality. METHODS: Data from the first four annual screens, denoted T0–T3, are reported. A CA 125 value at or above 35 units/mL or an abnormality on transvaginal ultrasonography was considered a positive screen. Diagnostic follow-up of positive screens was performed at the discretion of participants’ physicians. Diagnostic procedures and cancers were tracked and verified through medical records. RESULTS: Among 34,261 screening arm women without prior oophorectomy, compliance with screening ranged from 83.1% (T0) to 77.6% (T3). Screen positivity rates declined slightly with transvaginal ultrasonography, from 4.6 at T0 to 2.9–3.4 at T1–T3; CA 125 positivity rates (range 1.4–1.8%) showed no time trend. Eighty-nine invasive ovarian or peritoneal cancers were diagnosed; 60 were screen detected. The positive predictive value (PPV) and cancer yield per 10,000 women screened on the combination of tests were similar across screening rounds (range 1.0–1.3% for PPV and 4.7–6.2 for yield); however, the biopsy (surgery) rate among screen positives decreased from 34% at T0 to 15–20% at T1–T3. The overall ratio of surgeries to screen-detected cancers was 19.5:1. Seventy-two percent of screen-detected cases were late stage (III/IV). CONCLUSION: Through four screening rounds, the ratio of surgeries to screen-detected cancers was high, and most cases were late stage. However, the effect of screening on mortality is as yet unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov , NCT00002540 LEVEL OF EVIDENCE: II