Universal Urine Drug Screening with Rapid Confirmation upon Admission to Labor and Delivery.

OBJECTIVE: This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results. STUDY DESIGN: Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018-March 2019) and after (phase 2, October 2019-September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS. The turnaround time for LC-MS was 1 week in phase 1 and 24 hours in phase 2. For mothers with positive LC-MS confirmation, the infant's meconium was sent for drug screening. Positive results were determined to be true or false positive based on urinary LC-MS results. The primary outcome was the rate of opioid-positive mothers who were unanticipated. The secondary outcome was the difference in rate of neonates who were observed for NOWS, before and after implementation of RC with LC-MS. RESULTS: In phase 2, a total of 2,395 deliveries occurred of which 2,122 (88.6%) had available UDS results. Fifty-two (2.5%) women had a positive UDS for at least one drug with LC-MS confirmation. Of those, 25 were true positive and 27 were false positive. Twenty-one (84%) true positive mothers were taking opioids and 8 (37%) of them were unanticipated positives. Among mothers with positive UDS for opioids, the neonatal observation rate for development of NOWS was 100% (22/22) and 48% (21/44) before and after implementation of LC-MS RC, respectively. CONCLUSION: Universal UDS and LC-MS RC in L&D may improve detection of unanticipated positive mothers whose infants are at risk of NOWS. RC of positive results allows intervention only for confirmed cases. KEY POINTS: · Universal UDS can detect more infants at risk of NOWS.. · Rapid confirmation of positive UDS reduces burden.. · Only confirmed infants should be observed in the neonatal intensive care unit.. · Child Protective Services should only be notified of confirmed opioid-positive results..

Age-associated trends of vulvar cancer in the US.

OBJECTIVE: Medical societies have over the years moved away from recommending routine pelvic examinations in older, asymptomatic women above age 65. Consequently, vulvar examination is a largely neglected component of the physical examination, unless sent to a specialist for gynecological evaluation. In recognition of these recommendations, we analyzed US trends in vulvar cancer incidence, age, and stage at diagnosis, survival, and association with human papillomavirus (HPV). METHODS: Cases of vulvar and cervical cancer from 1992 to 2014 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results and Centers for Disease Control's data on age at diagnosis, stage of disease, and HPV-association were analyzed and compared. Incidence and mortality rates were extracted and calculated. RESULTS: From 1992-2014, there was a 14.3% increase in vulvar cancer rates. The absolute average incidence rate was 2.25, with HPV still being seen in vulvar carcinomas in women 65 years and above. Cervical cancer mortality rates declined by 34.2%, while vulvar cancer death rates were unchanged. We show increased intervals for cervical cancer screening is associated with later stage vulvar cancer detection. The proportion of vulvar cancer cases diagnosed in women age <50 steadily decreased, from 42.05% of cases in 1992-1996 to 19.75% of total cases in 2012-2015. Meanwhile, vulvar cancer cases diagnosed in women > 65 yo increased from 36.62% of cases in 1992-1996 to 49.82% of cases in 2012-2015. CONCLUSION: The incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years, with HPV (+) tumors occurring into 70's and 80's. Though medical societies do not routinely recommend an external genital examination in women 65 years and above, we show this is a missed opportunity to improve cancer outcomes in some older females.

Video Summary:http://links.lww.com/MENO/A678.

Detection of high-risk human papillomavirus RNA in urine for cervical cancer screening with HPV 16 & 18/45 genotyping.

OBJECTIVE: To detect high-risk human papillomavirus (hrHPV) messenger-RNA (mRNA) in urine samples, compare their concordance with cervical samples including HPV 16 & 18/45 genotyping, and to determine the utility in detecting ≥ CIN 2 lesions. METHODS: A cohort of 189 non-pregnant patients (age ≥ 25) was recruited in three groups: Group 1 with abnormal pap-smears and hrHPV positivity, Group 2 with normal pap-smears and hrHPV positivity, and Group 3 with normal pap-smears and hrHPV negativity. Urine samples were tested for hrHPV-mRNA and subsequent hrHPV-mRNA genotype if positive. High-risk HPV detection and genotyping were performed using Aptima assays which are validated for cervical HPV testing. Colposcopy results from groups 1 & 2 were analyzed. RESULTS: The sensitivity of urine hrHPV-mRNA detection was 31.5% while the specificity and PPV were above 95% (96.9% & 95.1% respectively) (p < 0.001). The kappa agreement with cervical samples was fair (0.22, p = 0.04). The sensitivity and specificity of urine hrHPV-mRNA genotyping were 20.0% & 100% respectively (p < 0.001) with 100% genotype-specific concordance. The kappa agreement with cervical samples was fair (0.25, p = 0.16). For urine hrHPV-mRNA detection of ASC-H/HSIL when grouped by age ≥ 30, the sensitivity and specificity were 45.4% & 63.9% respectively (p = 0.009). For urine hrHPV-mRNA detection of ≥ CIN 2 for all ages, the sensitivity and specificity were 45.5% & 75.0% respectively (p = 0.03). CONCLUSION: Using the Aptima Assay, urine hrHPV-mRNA detection is suboptimal for cervical cancer screening but given the high specificity, it has the potential to identify high-grade lesions (≥ CIN 2). Urine hrHPV-mRNA genotyping via this modality is not beneficial in triage settings of normal or abnormal cytology to determine the need for colposcopy.

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

BACKGROUND: Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. METHODS: Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. RESULTS: We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. CONCLUSION: Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.

Endonuclease-resistant DNA: a novel histochemical marker for cervical intraepithelial neoplasia and cervical carcinoma.

The diagnosis of cervical intraepithelial neoplasia (CIN) has low interobserver reproducibility. The pathogenesis of human papillomavirus (HPV) from infection to high-grade CIN is well understood. In benign lesions, HPV-DNA is often packaged into virions, whereas malignant transformation disrupts virion assembly. It is conceivable that if cervical lesions were exposed to endonuclease digestion, HPV virions would alter nuclear susceptibility to DNA degradation. We propose that susceptibility to endonuclease digestion can serve as a simple marker to identify CIN grade. From paraffin-embedded tissue blocks, condyloma accuminata, CIN I-III, and cervical carcinoma cases were identified. Sections were placed in a bath containing DNAse I for DNA digestion. Residual DNA was stained by a Feulgen process. Endonuclease-resistant DNA (erDNA) staining was correlated to disease grade. In addition, 10 HPV (+) patients whose infection regressed and 8 whose infection progressed to CIN II or above had their initial HPV lesions stained for erDNA. erDNA was observed in 81% condylomas and 80% CIN I cases. All CIN II, III, and cancer cases were endonuclease sensitive with 100% of lesions showing no staining. Eighty percent of HPV lesions that regressed had erDNA staining, whereas 75% lesions that progressed had no erDNA staining. The spectrum of cervical disease caused by HPV has different susceptibilities to endonuclease digestion, which may aid in the diagnosis of CIN. Furthermore, in our small pilot study, erDNA status was associated with the clinical outcomes. Prospective studies are needed to confirm this observation. erDNA status is a promising novel biomarker.