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Human papillomavirus (HPV) testing for cervical screening increases diagnosis of precancer and reduces the incidence of cervical cancer more than cytology alone. However, real‐world evidence from diverse practice settings is lacking for the United States (U.S.) to support clinician adoption of primary HPV screening. Using a population‐based registry, which captures all cervical cytology (with or without HPV testing) and all cervical biopsies, we conducted a real‐world evidence study of screening in women aged 30 to 64 years across the entire state of New Mexico. Negative cytology was used to distinguish cotests from reflex HPV tests. A total of 264 198 cervical screening tests (with exclusions based on clinical history) were recorded as the first screening test between 2014 and 2017. Diagnoses of cervical intraepithelial neoplasia grades 2 or 3 or greater (CIN2+, CIN3+) from 2014 to 2019 were the main outcomes. Of cytology‐negative screens, 165 595 (67.1%) were cotests and 4.8% of these led to biopsy within 2 years vs 3.2% in the cytology‐only group. Among cytology‐negative, HPV tested women, 347 of 398 (87.2%) CIN2+ cases were diagnosed in HPV‐positive women, as were 147 of 164 (89.6%) CIN3+ cases. Only 29/921 (3.2%) CIN3+ and 67/1964 (3.4%) CIN2+ cases were diagnosed in HPV‐negative, cytology‐positive women with biopsies. Under U.S. opportunistic screening, across a diversity of health care delivery practices, and in a population suffering multiple disparities, we show adding HPV testing to cytology substantially increased the yield of CIN2+ and CIN3+. CIN3+ was rarely diagnosed in HPV‐negative women with abnormal cytology, supporting U.S. primary HPV‐only screening. [ABSTRACT FROM AUTHOR]

Hepatocellular Carcinoma ( HCC) incidence is increasing in the USA. Gemcitabine (G) and oxaliplatin (O) are active in HCC and biliary duct cancer ( BDC). Erlotinib (E) is an EGFR tyrosine kinase inhibitor ( TKI) with known activity against both. We sought to evaluate the efficacy of the combination G+O+E. Patients with either of the two diagnosis were treated in a phase II trial. Simons 2 stage design was used. A disease-control rate ( DCR), complete response ( CR) + partial response ( PR)+ stable disease ( SD) at 24 weeks of ≤20% and >40% (P0 and P1 of 0.2 and 0.4, respectively) were set as undesirable (null) and desirable results. 26 HCC and 7 BDC patients were accrued. In HCC, 1 PR, 10 SD, and 9 PDs were seen. DCR in HCC was 42%. Among seven (7) patients with BDC, one patient was not evaluable; one achieved a long lasting PR, and five patients had SD and DCR was 86%. Median overall survival ( OS) times and progression-free survivals ( PFS) were 196 and 149 days in HCC and 238 days and not reached in BDC. PFS at 26 weeks in HCC was 41% and at 21 weeks in BDC was 60%. Grade 3 toxicities in >5% of patients were fatigue (12.9%), neutropenia (9.6%), thrombocytopenia (9.6%), and diarrhea (6.4%). G+O+E exceeded both preset P0a and P1 of the primary objective with a PFS of 41% at 26 weeks for HCC and preliminary BDC data may warrant further investigations. [ABSTRACT FROM AUTHOR]

Background: The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media., Objective: The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated., Study Design: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods., Results: The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66., Conclusion: The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The rates of SMM have been steadily increasing in Arkansas, a southern rural state, which has the 5th highest maternal death rate among the US states. The aims of the study were to test the functionality of the Bateman index in association to SMM, in clustering the risks of pregnancies to SMM, and to study the predictability of SMM using the Bateman index., Study Design: From the ANGELS database, 72,183 pregnancies covered by Medicaid in Arkansas between 2013 and 2016 were included in this study. The expanded CDC ICD-9/ICD-10 criteria were used to identify SMM. The Bateman comorbidity index was applied in quantifying the comorbidity burden for a pregnancy. Multivariable logistic regressions, KMeans method, and five widely used predictive models were applied respectively for each of the study aims., Results: SMM prevalence remained persistently high among Arkansas women covered by Medicaid (195 per 10,000 deliveries) during the study period. Using the Bateman comorbidity index score, the study population was divided into four groups, with a monotonically increasing odds of SMM from a lower score group to a higher score group. The association between the index score and the occurrence of SMM is confirmed with statistical significance: relative to Bateman score falling in 0-1, adjusted Odds Ratios and 95% CIs are: 2.1 (1.78, 2.46) for score in 2-5; 5.08 (3.81, 6.79) for score in 6-9; and 8.53 (4.57, 15.92) for score ≥10. Noticeably, more than one-third of SMM cases were detected from the studied pregnancies that did not have any of the comorbid conditions identified. In the prediction analyses, we observed minimal predictability of SMM using the comorbidity index: the calculated c -statistics ranged between 62% and 67%; the Precision-Recall AUC values are <7% for internal validation and <9% for external validation procedures., Conclusions: The comorbidity index can be used in quantifying the risk of SMM and can help cluster the study population into risk tiers of SMM, especially in rural states where there are disproportionately higher rates of SMM; however, the predictive value of the comorbidity index for SMM is inappreciable.

Objectives: Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we document the state-wide uptake of co-testing with HPV and cytology in women aged 30-64 years as recommended by national and international bodies., Methods: Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21-64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology., Results: A total of 1,704,055 cervical screening tests from 681,440 women aged 21-64 years in the state of New Mexico were identified. The proportion of screening tests which were co-tests rose from 5.6% in 2008 to 84.3% in 2019 among women aged 30-64 years with a marked change from the near exclusive use of the Hybrid Capture II HPV test, (a signal amplified test method) to the use of target amplified HPV tests. The largest increases were seen between 2013 and 2015, reflecting the introduction and adoption of new clinical guidelines. Increases in co-testing were also seen in younger women., Conclusions: Co-testing is now well established in women aged 30-64 years, but smaller increases have also been seen at younger ages, although this is not currently recommended. The impact of co-testing on cervical disease outcomes and number of colposcopies and biopsies in routine population settings remain important, especially in young women., Competing Interests: Declaration of competing interest JC and CMW have received funds from grants, cooperative agreements or subcontracts related to cervical screening and triage through their respective institutions. JC reports personal fees from Hologic and grants from Becton Dickinson (BD), Qiagen and Gene First all outside the submitted work. CMW reports receiving reagents and equipment from Roche Molecular Systems, Roche/Ventana Medical Systems, Hologic and Genera Biosystems, research funding from Hologic all through her institution and outside of the submitted work, personal fees from BD. All other authors report no potential conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)