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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.

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 18-30years). When asked about HPV-related cancer types, the correct response increased from 28.4% (pre-intervention) to 51.9% (post-intervention; p

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.

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.

Background: Cervical cancer (CC) is the 4th most commonly diagnosed cancer among women, with approximately 528,000 new cases annually. Current screening approaches for this disease have certain limitations; Pap tests require dedicated cytopathology infrastructure, while human papillomavirus (HPV) DNA testing may lead to invasive procedures in patients with transient infection. Liquid biopsy has emerged as a minimally invasive approach to detect and monitor disease progression and treatment response. We and others have previously demonstrated the clinical utility of circulating tumor (ct)DNA to monitor HPV+ cancers. Moreover, cell free (cf)DNA fragmentation patterns have been found to be a biomarker of disease burden. This cfDNA is thought to originate largely as a result of cell death, where small fragments of ~167 bp are associated with apoptosis and larger fragments (>1000 bp) are associated with necrosis. Despite advances in liquid biopsy techniques, little is known about the composition of cfDNA from different analytes in CC patients. Methods: The aim of this study was to compare the presence and composition of cfDNA from different liquid biopsy analytes in patients with CC and high grade cervical intraepithelial neoplasia or dysplasia (CIN/CD). Blood, urine, and vaginal swabs were collected from 20 patients with CC and 9 patients with CIN/CD at the McGill University Health Centre. All samples were centrifuged twice to isolate supernatant. Samples were tested for HPV ctDNA by ddPCR. Analysis of fragment length was performed using the Agilent Bioanalyzer 2100. Dominant fragment was determined as the DNA fragment with the highest concentration, while overall fragment was calculated as the average fragment across all bioanalyzer peaks. Results: HPV16/18 ctDNA was detectable 14/20 CC patients and 2/6 CIN patients, and 0/3 CD patients in plasma, urine, and vaginal swab. Concordance for all sample types tested was seen in 90% of cases. On average, fragment analysis demonstrated 174, 195, and 183 bp dominant small fragments in plasma, urine and vaginal swab, respectively. Plasma samples showed only smaller fragments (range: 168-187 bp). Other analytes displayed a predominance of larger cfDNA, with an overall fragment size of 3996 and 5194 bp in urine and vaginal swab, respectively. Conclusions: HPV-DNA was detectable in all analytes sampled in patients with CC and CIN, with a trend of higher detection in CC samples. The fragmentation patterns of cfDNA varied between patients and within patients across analytes, with larger fragments - likely of necrotic origin - seen only in urine and vaginal swab cfDNA. Smaller fragments - likely related to apoptosis - were seen across all sample types studied. Overall, analysis of fragmentation may provide valuable insight into cfDNA origins in different sample types and provide a novel biomarker for diagnosis and surveillance. Citation Format: Sarah Tadhg Ferrier, Erica Mandato, Alexandra Bartolomucci, Thupten Tsering, Shuk On Annie Leung, Julia Valdemarin Burnier. Cell free DNA levels and fragmentation patterns in different liquid biopsy analytes (blood, urine and vaginal fluid) in cervical cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5596.

Simple Summary There is limited information about genomic markers, especially for cervical adenocarcinoma treatment decisions. In this prospective study, it was found that nonsynonymous PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. It is the first indication of the predictive power of PIK3CA aberration in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for the prolonged strategy of surveillance and indicates the possibility of tailoring management of this particular women’s cancer. Abstract Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

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...

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

Highlights • 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.

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. Keywords: Human papillomavirus, Vaccine, Healthcare provider, Education