The effect of carbomer versus noncarbomer lubricant on the adequacy of cervical cytology specimens.

Introduction: Cervical cytology remains a critical screening tool for cervical cancer. While various factors can influence cytology quality, the effect of lubricant type used during specimen collection has been previously studied with inconclusive results. This study aimed to evaluate the impact of surgical lubricant on cervical cytology results and elucidate risk factors associated with unsatisfactory results.

Meeting report: Considerations for trial design and endpoints in licensing therapeutic HPV16/18 vaccines to prevent cervical cancer.

Cervical cancer is a major cause of morbidity and mortality globally with a disproportionate impact on women in low- and middle-income countries. In 2021, the World Health Organization (WHO) called for increased vaccination, screening, and treatment to eliminate cervical cancer. However, even with widespread rollout of human papillomavirus (HPV) prophylactic vaccines, millions of women who previously acquired HPV infections will remain at risk for progression to cancer for decades to come.

Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex in mice during decision making.

Attention supports decision making by selecting the features that are relevant for decisions. Selective enhancement of the relevant features and inhibition of distractors has been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when relevance cannot be directly determined, and the attention signal needs to be internally constructed is less understood.

Combined Treatment of Uterine Leiomyosarcoma with Gamma Secretase Inhibitor MK-0752 and Chemotherapeutic Agents Decreases Cellular Invasion and Increases Apoptosis.

Due to limited effective therapeutics for uterine leiomyosarcoma (uLMS), the impact of the gamma secretase inhibitor (GSI) MK-0752 with common chemotherapeutics was explored in uLMS. MTT assays were performed on two human uLMS cell lines, SK-UT-1B and SK-LMS-1, using MK-0752, docetaxel, doxorubicin, and gemcitabine, individually and in combination, to determine cell viability after treatment. Synergistic combinations were used in transwell invasion assays, cell cycle flow cytometry, proliferation assays, and RNA sequencing.

Structure and transcription of integrated HPV DNA in vulvar carcinomas.

HPV infections are associated with a fraction of vulvar cancers. Through hybridization capture and DNA sequencing, HPV DNA was detected in five of thirteen vulvar cancers. HPV16 DNA was integrated into human DNA in three of the five.

Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

Background: Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort.

2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023.

This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study.

Background: Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer.

Methods: PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100-199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled.

Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex during decision making.

Attention is a cognitive faculty that selects part of a larger set of percepts, driven by cues such as stimulus saliency, internal goals or priors. The enhancement of the attended representation and inhibition of distractors have been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when the cue has to be internally constructed from conflicting stimuli, decision rules, and reward contingencies, is less understood.

Continuous multiplexed population representations of task context in the mouse primary visual cortex.

Effective task execution requires the representation of multiple task-related variables that determine how stimuli lead to correct responses. Even the primary visual cortex (V1) represents other task-related variables such as expectations, choice, and context. However, it is unclear how V1 can flexibly accommodate these variables without interfering with visual representations.

Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.

Background: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined.

Primary Human Papillomavirus Testing and Other New Technologies for Cervical Cancer Screening.

Cervical cancer screening has saved the lives of millions in regions where routine gynecologic care is readily accessible. As screening continues to evolve away from cervical cytology to primary human papillomavirus (HPV) testing, robust prospective cohort data have allowed for precise risk stratification and improved our ability to identify those at greatest risk of high-grade dysplasia and decrease unnecessary diagnostic procedures. New technologies such as p16/Ki-67 dual stain testing and HPV methylation panels, which offer comparable performance to co-testing and can be developed into high-throughput workflows, could lead to a fully molecular Pap test.

Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

Background: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission.

Methods: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center.

Confusion and anxiety in between abnormal cervical cancer screening results and colposcopy: "The land of the unknown".

Objective: Attendance to colposcopy after abnormal cervical cancer screening is essential to cervical cancer prevention. This qualitative study explored patients' understanding of screening results, their experiences of the time leading up to the colposcopy appointment, and colposcopy.

Methods: We recruited women referred for colposcopy from two urban practices in an academic health system.

Barriers and facilitators to effective cervical cancer screening in Belize: a qualitative analysis.

Purpose: Belize has among the highest cervical cancer incidence and mortality rates of Latin American and Caribbean countries. This study evaluates the perspectives of key stakeholders for cervical cancer screening in Belize and identifies the barriers and facilitators for providing equitable access to prevention services.

Methods: Semi-structured interviews discussing cervical cancer screening were conducted with key stakeholders across the six districts of Belize in 2018.

Construct validity and responsiveness of a health-related symptom index for persons either treated or monitored for anal high-grade squamous intraepithelial lesions (HSIL): AMC-A01/-A03.

Purpose: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI).

Methods: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point.

Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1.

Unlabelled: Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. The safety run-in cohort of a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein "TA-CIN"] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1 (NCT03911076) was recently completed.

Quality Assurance in Clinical Trials Requiring Radiation Therapy in Sub-Saharan Africa.

Purpose: Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe.

Short- and Long-Term Outcomes for Ethnic Minorities in the United States After Liver Transplantation: Parsing the Hispanic Paradox.

Background: Racial and ethnic minorities are disproportionally affected by end-stage liver disease. Unfortunately, disparities in referrals to liver transplantation (LT), organ allocation, and posttransplant outcomes exist in this population.

Methods: We performed a retrospective analysis of patients over the age of 18 years undergoing LT in the United States using the Scientific Registry of Transplant Recipients from 2002 to 2016.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

Background: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.

Gamma Secretase Inhibitors as Potential Therapeutic Targets for Notch Signaling in Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch family genes and proteins and to investigate the therapeutic effect of γ-secretase inhibitors (GSIs), indirect inhibitors of Notch signaling, in uLMS.

Design of the ANal Cancer/HSIL Outcomes Research study (ANCHOR study): A randomized study to prevent anal cancer among persons living with HIV.

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.

Multisite Clinical Validation of Isothermal Amplification-Based SARS-CoV-2 Detection Assays Using Different Sampling Strategies.

Isothermal amplification-based tests have been introduced as rapid, low-cost, and simple alternatives to real-time reverse transcriptase PCR (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. The clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP coronavirus disease of 2019 [COVID-19] detection test and OptiGene COVID-19 direct plus RT-loop-mediated isothermal amplification [LAMP] test) was compared with that of clinical RT-PCR assays using different sampling strategies. A total of 1,378 participants were tested across 4 study sites.

Cervical cancer prevention and control in women living with human immunodeficiency virus.

Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers.