Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary.

Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels.Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC.Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC.

Dysregulation of Cholesterol Homeostasis in Ovarian Cancer.

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer.

An Interactive Educational Tool to Improve Human Papillomavirus Vaccine Knowledge and Recommendation Among Nurses.

In United States, only 57% of  women and 53% of men in the recommended age groups have received all recommended doses of the human papillomavirus (HPV) vaccine. Healthcare provider education has been associated with strong vaccine recommendation and vaccination uptake. Our objective was to create a 7-min interactive online educational tool to improve knowledge and willingness to recommend the HPV vaccine among nurses. This is a prospective pre-test/post-test study to evaluate the effectiveness of the educational tool consisting of 10 flashcards in a question-answer format. Oncology nurses at our cancer center were invited to participate by email, which led them to the educational tool (i.e., intervention) along with pre- and post-test questions on HPV-associated cancers, vaccine-eligible age groups, dosing schedules, adverse events, and willingness to recommend. Of the 110 participants (mean age of 41.2 ± 11.4, 98% female, 64% >10 years of practice), there was improvement in knowledge after intervention in HPV-associated cancers (81% to 97%; p = 0.02), percentage of cervical caused by HPV (33% to 64%; p < 0.05), and dosing schedule (47% to 93%; p < 0.05). All participants correctly stated that continued screening is needed after vaccination both pre- and post-intervention. Eighty-five percent strongly agreed that the intervention improved their HPV knowledge, and 77% stated they were more likely to recommend the HPV vaccine after the intervention. While nurses are willing to recommend the vaccine, there remains persistent knowledge gaps. A brief 7-min self-administered online interactive flashcard educational intervention is effective in improving the HPV vaccine knowledge among nurses.

COVID-19 as a catalyst for reimagining cervical cancer prevention.

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

AACC Guidance Document on Cervical Cancer Detection: Screening, Surveillance, and Diagnosis.

BACKGROUND: Persistent genital infection with high-risk human papilloma virus (hrHPV) causes the vast majority of cases of cervical cancer. Early screening, ongoing surveillance, and accurate diagnosis are crucial for the elimination of cervical cancer. New screening guidelines for testing in asymptomatic healthy populations and management guidelines for managing abnormal results have been published by professional organizations. CONTENT: This guidance document addresses key questions related to cervical cancer screening and management including currently available cervical cancer screening tests and the testing strategies for cervical cancer screening. This guidance document introduces the most recently updated screening guidelines regarding age to start screening, age to stop screening, and frequencies of routine screening as well as risk-based management guidelines for screening and surveillance. This guidance document also summarizes the methodologies for the diagnosis of cervical cancer. Additionally, we propose a report template for human papilloma virus (HPV) and cervical cancer detection to facilitate interpretation of results and clinical decision-making. SUMMARY: Currently available cervical cancer screening tests include hrHPV testing and cervical cytology screening. The screening strategies can be primary HPV screening, co-testing with HPV testing and cervical cytology, and cervical cytology alone. The new American Society for Colposcopy and Cervical Pathology guidelines recommend variable frequencies of screening and surveillance based on risk. To implement these guidelines, an ideal laboratory report should include the indication for the test (screening, surveillance, or diagnostic workup of symptomatic patients); type of test (primary HPV screening, co-testing, or cytology alone); clinical history of the patient; and prior as well as current testing results.

Human Papillomavirus (HPV) Education and Knowledge Among Medical and Dental Trainees.

Persistent human papillomavirus (HPV) infection is responsible for the majority of oropharyngeal and cervical cancers in the USA. Currently, HPV curricula within medical and dental schools are not standardized. As such, we implemented a brief online educational intervention to increase medical and dental trainees' knowledge of the HPV vaccine and the association between HPV and cancer. The objectives of this study were to (1) assess medical and dental trainees' baseline knowledge regarding HPV and HPV vaccine, (2) determine the willingness to recommend the HPV vaccine to patients, and (3) evaluate the impact of an online intervention on HPV-related knowledge. Medical and dental trainees from two large academic centers in the USA were asked to fill out an online pre-intervention questionnaire, followed by a 10-min HPV educational intervention based on the Center of Disease Control and Prevention (CDC) resources, and then a post-intervention questionnaire. There were 75 participants (67.4% females; median age 18-30 years). When asked about HPV-related cancer types, the correct response increased from 28.4% (pre-intervention) to 51.9% (post-intervention; p < 0.01). When asked about the prevalence of HPV infections, the correct response improved from 36 to 72% (p < 0.01). There was also a 25.2% improvement in identifying the correct HPV vaccination dosing schedule (p < 0.01). Eighty-seven percent of the participants mentioned that the online education improved their HPV knowledge, and 68.5% reported that they were more likely to recommend HPV vaccine after the online intervention. The proposed online educational intervention was effective at improving HPV-related cancer and HPV vaccine knowledge as well as attitudes towards vaccine recommendation among dental and medical trainees and could be implemented in medical and dental school curricula in the future.

Next-Generation Sequencing in the Diagnosis of Metastatic Lesions: Reclassification of a Glioblastoma as an Endometrial Cancer Metastasis to the Brain.

Endometrial cancer is the most common gynecologic cancer in the U.S., but metastasis to the brain is rare, and diagnosis can be challenging. Traditional tools for determining if a tumor is a primary or metastatic lesion include pan-imaging, histopathologic studies, and immunohistochemistry. Molecular testing with next-generation sequencing has been increasingly used to augment these tests. We present a case of a patient who initially presented with a brain lesion diagnosed as glioblastoma on histology and immunohistochemistry, but whose diagnosis was later changed to metastasis from an endometrial primary based on molecular findings. The two tumors shared a common microsatellite instability signature and 51 DNA variants, including oncogenic driver mutations KRAS p.G13D, PIK3CA p.E545A, and PTEN p.I135V and p.K267Rfs*9. This highlights the power of molecular analysis in making the diagnosis in cases of rare metastases. KEY POINTS: Brain metastasis from endometrial primary is rare, and histopathological features may be augmented with molecular analysis to aid in diagnosis. Comparison of the molecular makeup of the primary endometrial lesion with the metastatic lesion may reveal high-risk molecular features that may be indicative of metastatic potential.

Loop Electrosurgical Excision Procedure in Managing Persistent Low-Grade Abnormality or Human Papillomavirus Positivity.

OBJECTIVES: The aims of the study were to estimate the rate and to identify predictors of high-grade abnormalities among women with persistent low-grade abnormalities or high-risk human papillomavirus (hrHPV) positivity for at least 2 years stratified by presence (high risk) or absence (low risk) of previous high-grade results or HPV 16/18. MATERIALS AND METHODS: A retrospective cohort study of patients who underwent a loop electrosurgical excision procedure (LEEP) for persistent low-grade or hrHPV positivity was performed. Patients were stratified based on whether they had a history of high-grade and/or HPV 16/18 positivity. Rates of high-grade or worse abnormalities on LEEP were compared using Fisher exact tests. Logistic regression was used to evaluate the associations between patient characteristics and high-grade results on the LEEP. RESULTS: Three hundred eleven LEEPs were performed for persistent low-grade or hrHPV positivity. The rates of occult high grade were 12% and 22% among the low- and high-risk groups, respectively. Compared with those 45 years and older, the adjusted odds of high grade was 3.79 (95% CI = 1.19-12.1) for women aged 25-29 years. The odds of high grade was higher among current versus never smokers (6.40; 95% CI = 2.01-20.4) and those with a history of high-grade abnormality (2.23; 95% CI = 1.12-4.43). At 2 years, approximately half had an abnormal cytology and/or hrHPV positivity result independent of whether high grade was identified on their LEEP specimen. CONCLUSIONS: Patients with persistent low-grade abnormalities or persistent hrHPV should be counseled on the risks and benefits of a LEEP given that 12%-22% have a risk of occult high grade, especially if they have a history of high-grade dysplasia.

Advances in the treatment of platinum resistant epithelial ovarian cancer: an update on standard and experimental therapies.

Introduction: Platinum-resistant ovarian cancer (PROC) is broadly defined as disease recurrence within 6 months of completing platinum-based chemotherapy, either in the primary or recurrent setting. Although there is significant heterogeneity, PROC is generally associated with poor outcomes and low response rates to standard chemotherapy. There have been novel developments in therapeutics for PROC based on biomarkers and a more nuanced understanding of DNA repair and immunologic pathways.Areas covered: This review provides a summary of standard of care and experimental therapies for patients with PROC. Recent advances in our understanding of the DNA damage response and immunobiology of ovarian cancer have paved the way for single agent and combinatorial strategies involving PARP inhibitors, cell cycle checkpoint inhibitors, and immune checkpoint inhibitors to overcome PARP resistance, capitalize on high replication stress, and promote effective anti-tumor immunity, respectively. Furthermore, novel agents including antibody drug conjugates, bispecific antibodies, and recombinant fusion proteins show promise as experimental treatment options.Expert opinion: Standard and experimental treatment options available to patients with PROC have expanded. Testing for BRCA status, tumor mutational burden, and mismatch repair deficiency is recommended to guide therapy. Clinical trial participation is strongly encouraged with a focus on biomarker-driven trials targeting specific patient populations. Novel approaches such as ADCs, bispecific antibodies, targeting the GAS6/AXL and Notch pathways, and oncolytic virotherapy show considerable promise as emerging therapies.

Triaging abnormal cervical cancer screening tests using p16INK4a detection by ELISA on fresh cervical samples.

PROBLEM: Cervical cancer screening strategies in the United States include cotesting (human papillomavirus (HPV) with cytology), primary HPV with genotyping and reflex cytology, and cytology alone. An ongoing challenge is the appropriate triage of patients to colposcopy to those at highest risk. We investigated whether incorporation of p16INK4a immunodetection by enzyme-linked immunosorbent assay (ELISA) on fresh cervical samples obtained at the time of screening could improve appropriate referral to colposcopy. METHOD OF STUDY: A derivation group comprised of cervical swabs collected from subjects with high-grade dysplasia or cancer (positive control) and from subjects with negative screening history (negative control). Samples collected from colposcopy were used to evaluate the existing screening strategies individually and with incorporation of p16INK4a ELISA. Histology was used as the gold standard. RESULTS: Among 163 subjects recruited, 138 were included. In the derivation group, mean p16INK4a level was 2.86 ng/mL (n = 31) and 0.58 ng/mL (n = 20) among positive and negative controls respectively (p = 0.002) with an area under the receiver operator characteristic curve of 0.79 (p < 0.001). Among colposcopy subjects, sensitivity/specificity for cotesting, primary HPV, and cytology were 94%/42%, 88%/45%, and 88%/49%, respectively. Incorporation of p16INK4a resulted in similar sensitivity and improved specificity (cotesting+p16 88%/58%, primary HPV+p16 88%/57%, cytology+p16 81%/62%; p = 0.23/p = 0.008) with decrease in colposcopy referrals by 15% to 22% (p = 0.01). CONCLUSIONS: These results demonstrate the feasibility of quantifying p16INK4a by ELISA in fresh cervical samples, and its potential as an adjunct to existing screening strategies in the identification of high grade-dysplasia while reducing the number of colposcopic referrals.

Female adnexal tumor of probable Wolffian Origin - A report of two cases at one institution.

•FATWOs are rare gynecologic neoplasms of low malignant potential derived from mesonephric (Wolffian) duct remnants.•FATWOs have diverse presentations from vague abdominal symptoms to incidental diagnosis.•In general, FATWOs require no additional management beyond initial surgical intervention.

Educating healthcare providers to increase Human Papillomavirus (HPV) vaccination rates: A Qualitative Systematic Review.

OBJECTIVES: HPV vaccination rates in the United States lag behind other developed countries. Educational interventions are primarily directed at patients and parents rather than healthcare providers (HCPs), despite evidence that provider recommendation is a key determinant of vaccine uptake. The objectives for this review are to synthesize the available evidence related to the knowledge, attitudes, and beliefs of HCPs surrounding HPV vaccination, to summarize provider-specific educational interventions which have been evaluated, and to review existing provider-specific educational resources from national organizations and whether they align with the gaps identified. METHODS: A systematic search was performed using PubMed, Web of Science, CINAHL, and ERIC with MeSH terms human papillomavirus, vaccine, education, workshop, training, knowledge, attitude, belief, intention, and healthcare provider. Full text articles were obtained for studies that described the knowledge and attitudes of providers and/or impact of educational interventions. Data extraction was performed by four independent reviewers. Websites of American organizations with an interest in HPV vaccination were manually searched for provider resources. RESULTS: 1066 publications were identified, and 98 articles were fully reviewed with 40 ultimately included. Providers' knowledge on HPV was generally low with a correspondingly low vaccine recommendation rate. Provider-specific education (e.g., didactic session and communication training) with complimentary interventions demonstrated increased knowledge and vaccine series initiation and completion. Themes identified in descriptive studies highlighted providers' lack of general HPV and vaccine knowledge, low self-confidence in counselling and addressing parental concerns, and discomfort in discussing sexual issues related to vaccination. Many American organizations have provider-specific resources; however, the effectiveness of these materials has not been established. CONCLUSIONS: HPV knowledge among providers remains low. Educational interventions to improve knowledge and communication appear to be effective. A breadth of resources from national organizations are available but their efficacy and level of utilization is largely unknown. Coordinated efforts are needed to evaluate provider-specific educational resources to improve vaccine uptake in the US.

When bad things happen to good surgeons: reactions to adverse events.

Adverse events are, unfortunately, common components of surgical practice. Much has been done to develop safer systems to prevent these adverse events; however, there has been less focus on the surgeon experiencing these events. This article presents a framework to understand surgeons' reactions to adverse events that was derived from a more recent study as well as a review of relevant psychology literatures. This framework is then situated within the broader picture of mindful practice to explore how the psychological and social dimensions of the surgeon can affect judgment and cognition.