Unindicated cervical cancer screening in adolescent females within a large healthcare system in the United States.

BACKGROUND: Current consensus recommendations are to not initiate cervical cancer screening for immunocompetent adolescent females before 21 years of age. This is in part because of the very low rate of 0.8 per 100,000 new cervical cancer cases diagnosed among women aged between 20 to 24 years. Timely human papillomavirus vaccination further decreases the incidence of cervical cancer to 4 cases per 100,000 persons by the age of 28 years. Screening before 21 years of age has demonstrated no clear benefit in cancer risk reduction or outcomes. In addition, unindicated screening among adolescents can lead to patient harm and increasing costs to the healthcare system. OBJECTIVE: It is important to assess the rates of overutilization of cervical cancer screening and to identify areas where improvements have occurred and where further opportunities exist. This study aimed to assess the trends over time and the practice and provider factors associated with unindicated cervical cancer screening tests in adolescent females within the largest healthcare system in the state. STUDY DESIGN: Cross-sectional data from patients aged 13 to 20 years who underwent cervical cancer screening between January 1, 2012, and December 31, 2018, across a large multihospital health system were reviewed. All cervical cancer screening results were included. The incidence rate of unindicated screening was analyzed over 6-month intervals using the Poisson regression analysis. RESULTS: The study included data from 118 providers and 794 women. Among the 900 screening results, most (90%) were unindicated: 87% with unindicated cytology testing alone and 14% with unindicated human papillomavirus testing. Screening tests were collected from patients aged 13 to 20 years, many of whom had multiple unindicated cytology tests, with 25 patients having ≥3 tests before the age of 21 years. Most results of cytology testing were negative for intraepithelial lesion or malignancy (77%). Moreover, 52 invasive diagnostic or therapeutic procedures (49 colposcopies and 3 conizations) were performed, of which 45 (87%) followed an unindicated screening test. Between 2012 and 2018, the incidence rate of unindicated cytology decreased by 33% (12.6 to 8.5 unindicated cytology per 1000 encounters). The incidence rate of unindicated screening was lower in the academic setting than in the community setting (incidence rate ratio, 0.43; P<.01). Even with decreases in the overall rates of unindicated screening throughout the study period, there were still 58 unindicated screening tests performed in the final year of this study. CONCLUSION: Despite substantial reductions in unindicated screening for women aged <21 years, there remained areas for improvement. Our data reflected practices of guideline nonadherence up to 7 years after the 2012 guideline. Now, with a new series of changes to the guidelines, which may be even more challenging for patients and providers, it is more important than ever to utilize evidence-based strategies to improve guideline dissemination and adherence.

Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity.

OBJECTIVE: Maternal obesity increases the incidence of excess adiposity in newborns, resulting in lifelong diabetes risk. Elevated intrauterine fetal adiposity has been attributed to maternal hyperglycemia; however, this hypothesis does not account for the increased adiposity seen in newborns of mothers with obesity who have euglycemia. We aimed to explore the placental response to maternal hyperinsulinemia and the effect of insulin-like growth factor 2 (IGF-2) in promoting fetal adiposity by increasing storage and availability of nutrients to the fetus. METHODS: We used placental villous explants and isolated trophoblasts from normal weight and obese women to assess the effect of insulin and IGF-2 on triglyceride content and insulin receptor signaling. Stable isotope tracer methods were used ex vivo to determine effect of hormone treatment on de novo lipogenesis (DNL), fatty acid uptake, fatty acid oxidation, and esterification in the placenta. RESULTS: Here we show that placentae from euglycemic women with normal weight and obesity both have abundant insulin receptor. Placental depth and triglyceride were greater in women with obesity compared with normal weight women. In syncytialized placental trophoblasts and villous explants, insulin and IGF-2 activate insulin receptor, induce expression of lipogenic transcription factor SREBP-1 (sterol regulatory element-binding protein 1), and stimulate triglyceride accumulation. We demonstrate elevated triglyceride is attributable to increased esterification of fatty acids, without contribution from DNL and without an acceleration of fatty acid uptake. CONCLUSIONS: Our work reveals that obesity-driven aberrations in maternal metabolism, such as hyperinsulinemia, alter placental metabolism in euglycemic conditions, and may explain the higher prevalence of excess adiposity in the newborns of obese women.

Time course analysis of RNA quality in placenta preserved by RNAlater or flash freezing.

PROBLEM: Preservation of biospecimen quality is critical to accurately and reliably assessing genes and proteins. We evaluated the effect of preparation method and storage duration on RNA quality in placenta and decidua. METHOD OF STUDY: Aliquots of nine placentas and decidua were placed in RNAlater® (RL) or flash frozen (FF) within 30 minutes of delivery. RNA was extracted immediately (baseline) and from matched samples stored at -80°C for 1 and 8-10 months. RNA Integrity Number (RIN) and housekeeping gene expression were quantified. RESULTS: At both time points, RL placenta had RIN and housekeeping gene Ct values similar to baseline. However, FF placenta had significantly lower RIN and higher Ct values at 1 and 8-10 months. In RL and FF decidua, RIN was unchanged from baseline. CONCLUSION: We found RNAlater more effectively and consistently preserved placenta, compared to flash freezing. However, for decidua, which is less dense than placenta, both modes yielded comparable RNA integrity over time.