Design of the HPV-automated visual evaluation (PAVE) study: Validating a novel cervical screening strategy.

Background: The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies. Methods: Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice. Results: Currently, sites have commenced fieldwork, and conclusive results are pending. Conclusions: The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide. Funding: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.

Design of the HPV-Automated Visual Evaluation (PAVE) Study: Validating a Novel Cervical Screening Strategy.

Objective: To describe the HPV-Automated Visual Evaluation (PAVE) Study, an international, multi-centric study designed to evaluate a novel cervical screen-triage-treat strategy for resource-limited settings as part of a global strategy to reduce cervical cancer burden. The PAVE strategy involves: 1) screening with self-sampled HPV testing; 2) triage of HPV-positive participants with a combination of extended genotyping and visual evaluation of the cervix assisted by deep-learning-based automated visual evaluation (AVE); and 3) treatment with thermal ablation or excision (Large Loop Excision of the Transformation Zone). The PAVE study has two phases: efficacy (2023-2024) and effectiveness (planned to begin in 2024-2025). The efficacy phase aims to refine and validate the screen-triage portion of the protocol. The effectiveness phase will examine acceptability and feasibility of the PAVE strategy into clinical practice, cost-effectiveness, and health communication within the PAVE sites. Study design: Phase 1 Efficacy: Around 100,000 nonpregnant women, aged 25-49 years, without prior hysterectomy, and irrespective of HIV status, are being screened at nine study sites in resource-limited settings. Eligible and consenting participants perform self-collection of vaginal specimens for HPV testing using a FLOQSwab (Copan). Swabs are transported dry and undergo testing for HPV using a newly-redesigned isothermal DNA amplification HPV test (ScreenFire HPV RS), which has been designed to provide HPV genotyping by hierarchical risk groups: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68. HPV-negative individuals are considered negative for precancer/cancer and do not undergo further testing. HPV-positive individuals undergo pelvic examination with collection of cervical images and targeted biopsies of all acetowhite areas or endocervical sampling in the absence of visible lesions. Accuracy of histology diagnosis is evaluated across all sites. Cervical images are used to refine a deep learning AVE algorithm that classifies images as normal, indeterminate, or precancer+. AVE classifications are validated against the histologic endpoint of high-grade precancer determined by biopsy. The combination of HPV genotype and AVE classification is used to generate a risk score that corresponds to the risk of precancer (lower, medium, high, highest). During the efficacy phase, clinicians and patients within the PAVE sites will receive HPV testing results but not AVE results or risk scores. Treatment during the efficacy phase will be performed per local standard of care: positive Visual Inspection with Acetic Acid impression, high-grade colposcopic impression or CIN2+ on colposcopic biopsy, HPV positivity, or HPV 16,18/45 positivity. Follow up of triage negative patients and post treatment will follow standard of care protocols. The sensitivity of the PAVE strategy for detection of precancer will be compared to current SOC at a given level of specificity.Phase 2 Effectiveness: The AVE software will be downloaded to the new dedicated image analysis and thermal ablation devices (Liger Iris) into which the HPV genotype information can be entered to provide risk HPV-AVE risk scores for precancer to clinicians in real time. The effectiveness phase will examine clinician use of the PAVE strategy in practice, including feasibility and acceptability for clinicians and patients, cost-effectiveness, and health communication within the PAVE sites. Conclusion: The goal of the PAVE study is to validate a screen-triage-treat protocol using novel biomarkers to provide an accurate, feasible, cost-effective strategy for cervical cancer prevention in resource-limited settings. If validated, implementation of PAVE at larger scale can be encouraged. Funding: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/NIH under Grant T32CA09168. Date of protocol latest review: September 24 th 2023.

Use of risk-based cervical screening programs in resource-limited settings.

Cervical cancer screening and management in the U.S. has adopted a risk-based approach. However, the majority of cervical cancer cases and deaths occur in resource-limited settings, where screening and management are not widely available. We describe a conceptual model that optimizes cervical cancer screening and management in resource-limited settings by utilizing a risk-based approach. The principles of risk-based screening and management in resource limited settings include (1) ensure that the screening method effectively separates low-risk from high-risk patients; (2) directing resources to populations at the highest cancer risk; (3) screen using HPV testing via self-sampling; (4) utilize HPV genotyping to improve risk stratification and better determine who will benefit from treatment, and (5) automated visual evaluation with artificial intelligence may further improve risk stratification. Risk-based screening and management in resource limited settings can optimize prevention by focusing triage and treatment resources on the highest risk patients while minimizing interventions in lower risk patients.

Comparison of accuracy and reproducibility of colposcopic impression based on a single image versus a two-minute time series of colposcopic images.

OBJECTIVE: Colposcopy is an important part of cervical screening/management programs. Colposcopic appearance is often classified, for teaching and telemedicine, based on static images that do not reveal the dynamics of acetowhitening. We compared the accuracy and reproducibility of colposcopic impression based on a single image at one minute after application of acetic acid versus a time-series of 17 sequential images over two minutes. METHODS: Approximately 5000 colposcopic examinations conducted with the DYSIS colposcopic system were divided into 10 random sets, each assigned to a separate expert colposcopist. Colposcopists first classified single two-dimensional images at one minute and then a time-series of 17 sequential images as 'normal,' 'indeterminate,' 'high grade,' or 'cancer'. Ratings were compared to histologic diagnoses. Additionally, 5 colposcopists reviewed a subset of 200 single images and 200 time series to estimate intra- and inter-rater reliability. RESULTS: Of 4640 patients with adequate images, only 24.4% were correctly categorized by single image visual assessment (11% of 64 cancers; 31% of 605 CIN3; 22.4% of 558 CIN2; 23.9% of 3412 < CIN2). Individual colposcopist accuracy was low; Youden indices (sensitivity plus specificity minus one) ranged from 0.07 to 0.24. Use of the time-series increased the proportion of images classified as normal, regardless of histology. Intra-rater reliability was substantial (weighted kappa = 0.64); inter-rater reliability was fair ( weighted kappa = 0.26). CONCLUSION: Substantial variation exists in visual assessment of colposcopic images, even when a 17-image time series showing the two-minute process of acetowhitening is presented. We are currently evaluating whether deep-learning image evaluation can assist classification.

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. Compared with standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic site from which the sample was collected. Sensitivity for nasopharyngeal sampling was 65.4% (range across study sites, 52.8% to 79.8%), for midturbinate was 88.2%, for saliva was 55.1% (range across study sites, 42.9% to 77.8%), and for anterior nares was 66.7% (range across study sites, 63.6% to 76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall, 82.7%) and those with a higher viral load (overall, 92.4% for cycle threshold [CT] of ≤25). Sensitivity and specificity of the OptiGene direct plus RT-LAMP test, which was conducted at a single study site, were 25.5% and 100%, respectively. The Atila iAMP COVID test with midturbinate sampling is a rapid, low-cost assay for detecting SARS-CoV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-CoV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption. IMPORTANCE Numerous SARS-CoV-2 detection assays have been developed and introduced into the market under emergency use authorizations (EUAs). EUAs are granted primarily based on small studies of analytic sensitivity and specificity with limited clinical validations. A thorough clinical performance evaluation of SARS-CoV-2 assays is important to understand the strengths, limitations, and specific applications of these assays. In this first large-scale multicentric study, we evaluated the clinical performance and operational characteristics of two isothermal amplification-based SARS-CoV-2 tests, namely, (i) iAMP COVID-19 detection test (Atila BioSystems, USA) and (ii) COVID-19 direct plus RT-LAMP test (OptiGene Ltd., UK), compared with those of clinical RT-PCR tests using different sampling strategies (i.e., nasopharyngeal, self-sampled anterior nares, self-sampled midturbinate, and saliva). An important specific use for these isothermal amplification-based, rapid, low-cost, and easy-to-perform SARS-CoV-2 assays is to allow for a safer return to preventive clinical encounters, such as cancer screening, particularly in low- and middle-income countries that have low SARS-CoV-2 vaccination rates.

Rethinking Cervical Cancer Screening in Brazil Post COVID-19: A Global Opportunity to Adopt Higher Impact Strategies.

The World Health Organization global call to eliminate cervical cancer encourages countries to consider introducing or improving cervical cancer screening programs. Brazil's Unified Health System (SUS) is among the world's largest public health systems offering free cytology testing, follow-up colposcopy, and treatment. Yet, health care networks across the country have unequal infrastructure, human resources, equipment, and supplies resulting in uneven program performance and large disparities in cervical cancer incidence and mortality. An effective screening program needs multiple strategies feasible for each community's reality, facilitating coverage and follow-up adherence. Prioritizing those at highest risk with tests that better stratify risk will limit inefficiencies, improving program impact across different resource settings. Highly sensitive human papillomavirus (HPV)-DNA testing performs better than cytology and, with self-collection closer to homes and workplaces, improves access, even in remote regions. Molecular triage strategies like HPV genotyping can identify from the same self-collected sample, those at highest risk requiring follow-up. If proven acceptable, affordable, cost-effective, and efficient in the Brazilian context, these strategies would increase coverage while removing the need for speculum exams for routine screening and reducing follow-up visits. SUS could implement a nationwide organized program that accommodates heterogenous settings across Brazil, informing a variety of screening programs worldwide.

Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies.

BACKGROUND: Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection. METHODS: Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites. RESULTS: Compared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively. CONCLUSIONS: The Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.

Design and feasibility of a novel program of cervical screening in Nigeria: self-sampled HPV testing paired with visual triage.

BACKGROUND: Accelerated global control of cervical cancer would require primary prevention with human papillomavirus (HPV) vaccination in addition to novel screening program strategies that are simple, inexpensive, and effective. We present the feasibility and outcome of a community-based HPV self-sampled screening program. METHODS: In Ile Ife, Nigeria, 9406 women aged 30-49 years collected vaginal self-samples, which were tested for HPV in the local study laboratory using Hybrid Capture-2 (HC2) (Qiagen). HPV-positive women were referred to the colposcopy clinic. Gynecologist colposcopic impression dictated immediate management; biopsies were taken when definite acetowhitening was present to produce a histopathologic reference standard of precancer (and to determine final clinical management). Retrospective linkage to the medical records identified 442 of 9406 women living with HIV (WLWH). RESULTS: With self-sampling, it was possible to screen more than 100 women per day per clinic. Following an audio-visual presentation and in-person instructions, overall acceptability of self-sampling was very high (81.2% women preferring self-sampling over clinician collection). HPV positivity was found in 17.3% of women. Intensive follow-up contributed to 85.9% attendance at the colposcopy clinic. Of those referred, 8.2% were initially treated with thermal ablation and 5.6% with large loop excision of transformation zone (LLETZ). Full visibility of the squamocolumnar junction, necessary for optimal visual triage and ablation, declined from 68.5% at age 30 to 35.4% at age 49. CIN2+ and CIN3+ (CIN- Cervical intraepithelial neoplasia), including five cancers, were identified by histology in 5.9 and 3.2% of the HPV-positive women, respectively (0.9 and 0.5% of the total screening population), leading to additional treatment as indicated. The prevalences of HPV infection and CIN2+ were substantially higher (40.5 and 2.5%, respectively) among WLWH. Colposcopic impression led to over- and under-treatment compared to the histopathology reference standard. CONCLUSION: A cervical cancer screening program using self-sampled HPV testing, with colposcopic immediate management of women positive for HPV, proved feasible in Nigeria. Based on the collected specimens and images, we are now evaluating the use of a combination of partial HPV typing and automated visual evaluation (AVE) of cervical images to improve the accuracy of the screening program.

A demonstration of automated visual evaluation of cervical images taken with a smartphone camera.

We examined whether automated visual evaluation (AVE), a deep learning computer application for cervical cancer screening, can be used on cervix images taken by a contemporary smartphone camera. A large number of cervix images acquired by the commercial MobileODT EVA system were filtered for acceptable visual quality and then 7587 filtered images from 3221 women were annotated by a group of gynecologic oncologists (so the gold standard is an expert impression, not histopathology). We tested and analyzed on multiple random splits of the images using two deep learning, object detection networks. For all the receiver operating characteristics curves, the area under the curve values for the discrimination of the most likely precancer cases from least likely cases (most likely controls) were above 0.90. These results showed that AVE can classify cervix images with confidence scores that are strongly associated with expert evaluations of severity for the same images. The results on a small subset of images that have histopathologic diagnoses further supported the capability of AVE for predicting cervical precancer. We examined the associations of AVE severity score with gynecologic oncologist impression at all regions where we had a sufficient number of cases and controls, and the influence of a woman's age. The method was found generally resilient to regional variation in the appearance of the cervix. This work suggests that using AVE on smartphones could be a useful adjunct to health-worker visual assessment with acetic acid, a cervical cancer screening method commonly used in low- and middle-resource settings.

Risk factors associated with delayed discharge following robotic assisted surgery for gynecologic malignancy.

BACKGROUND: The risk factors for extended length of stay (LOS) have not been examined in a cohort of patients with complex social and medical barriers who undergo robotic assisted (RA) surgery for gynecologic malignancies. We sought to identify those patients with a LOS > 24 h after robotic surgery and the risk factors associated with delayed discharge. Then we aimed to develop a predictive model for clinical care and identify modifiable pre-operative risk factors. METHODS: After IRB approval, data was abstracted from medical records of all patients with a gynecologic malignancy who underwent a RA laparoscopic surgery from 2010 to 2015. Univariable and multivariable logistic regression was performed to identify independent risk factors associated with delayed discharge defined as LOS > 24 h. A multi-variable logistic regression model was performed using a stepwise backward selection for the final prediction model. All testing was two-sided and a p-value < 0.05 was considered statistically significant. RESULTS: Of the 406 eligible and evaluable patients, 194 (48%) had a LOS > 24 h. Age ≥ 60 years, a higher usage of narcotic medication, a longer surgical time, and a larger estimated blood loss were all associated with LOS > 24 h (p < 0.05). Many of these women had a social work consultation and went home with home care services despite no surgical or post-operative complications. Our prediction model has the potential to correctly classified 75% of the patients discharged within 24 h. CONCLUSIONS: The development of a pre-hospitalization risk stratification and anticipating the possible need for home care services pre-operatively shows promise as a strategy to decrease LOS in patients classified as high-risk. These findings warrant prospective validation through the use of this prediction model in our institution.

Modified frailty index is predictive of wound complications in obese patients undergoing gynecologic surgery via a midline vertical incision.

OBJECTIVES: There are limited methods to identify which obese patients will experience wound complications after undergoing gynecologic surgery. We sought to determine the association between frailty and postoperative wound complications and to develop a prediction model for wound complications in this patient population. METHODS: We reviewed prospectively collected data of obese patients undergoing laparotomy though midline vertical incisions from 7/2013-3/2016. Modified frailty index (mFI) was calculated using 11 comorbidities previously validated. The primary outcome was the composite rate of postoperative wound complication. Data was analyzed using Fisher exact test or Chi-square and t-tests or Kruskal-Wallis tests. Poisson regression models were used to generate relative risks. Prediction models were created with receiver-operator characteristic curve analysis. RESULTS: Of 163 patients included, 56 (34%) were considered frail. Wound complications occurred in 52 patients (31.9%): 28 (50%) frail and 24 (22.4%) non-frail patients (RR 2.23, 95%CI 1.29-3.85). Frail patients had significantly greater frequencies of wound breakdown (37.5% vs 15%, RR 2.51, 95%CI 1.31-4.81). After controlling for BMI, tobacco use, and maximum postoperative glucose, frailty remained an independent predictor of wound complication (aRR 1.88, 95%CI 1.04-3.40). The area under the curve for the predictive model incorporating frailty was 0.73 for wound complications. CONCLUSION: Frailty is associated with wound complications in obese patients undergoing gynecologic surgery via a midline vertical incision and is a useful tool in identifying the most high risk patients. Further prospective research is necessary to incorporate mFI into preoperative planning and counseling.

Utilizing the Patient Reported Outcomes Measurement Information System (PROMIS®) to increase referral to ancillary support services for severely symptomatic patients with gynecologic cancer.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services. METHODS: English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO. RESULTS: Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%). CONCLUSIONS: Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.

Comparative Use of Napsin A and Glypican 3 to Distinguish Endometrial Clear Cell from Serous and Endometrioid Carcinomas.

OBJECTIVE: Diagnosis of endometrial clear cell carcinomas is difficult owing to the low reproducibility of histological cell type in high-grade endometrial cancers. Recently, immunoreactivity for napsin A and glypican 3 has been reported in clear cell cancers. We sought to evaluate the use of napsin A and glypican 3 staining to distinguish clear cell carcinoma from other high-grade endometrial cancers. METHODS/MATERIALS: Twenty cases of pure and mixed endometrial clear cell carcinoma were extracted from the 2000-2014 archival material in the Departments of Obstetrics & Gynecology and Pathology at Montefiore Medical Center and compared to serous and grade 3 endometrioid controls. Representative sections were stained with monoclonal antibodies to napsin A and glypican 3. Immunostains were independently reviewed by 2 pathologists to assess frequency and pattern of staining. Charts were reviewed for clinicopathologic and treatment data. RESULTS: Granular cytoplasmic positivity for napsin A was observed in 70% of endometrial clear cell carcinomas; only 25% showed cytoplasmic or membranous glypican 3 positivity. No serous or high-grade endometrioid tumors stained for either marker. No cases of clear cell carcinoma that stained negative for napsin A stained positive for glypican 3. No difference in the immunohistochemical profile was found between pure and mixed clear cell carcinomas and between early- and advanced-stage clear cell carcinomas. CONCLUSIONS: Napsin A is a more sensitive marker for endometrial clear cell carcinoma than glypican 3. In histologically ambiguous cases, napsin A and glypican 3 may help distinguish clear cell carcinoma from other high-grade histologies. Further investigation of endometrial clear cell carcinoma is needed to identify additional diagnostic tools for this rare histology. Correlation of a unique immunohistochemical profile and clinical outcomes is necessary.

Saddle pulmonary embolus resulting in cardiovascular collapse requiring extracorporeal membrane oxygenation in a postoperative patient with endometrial cancer.

BACKGROUND: Venous thromboembolism after open gynecologic surgery is not uncommon, especially in the presence of other risk factors such as obesity, prolonged surgical time or gynecologic malignancy. CASE: We present the case of a 62 y.o. patient who underwent open hysterectomy and surgical staging for uterine serous carcinoma. She was readmitted with lower extremity edema. During her workup, she underwent cardiovascular arrest secondary to saddle pulmonary embolus requiring cardiopulmonary resuscitation and extracorporeal membrane oxygenation. After systemic and catheter directed thrombolysis, and a long hospitalization, she was discharged home in stable condition. CONCLUSION: Saddle pulmonary embolus is a potentially catastrophic and fatal postoperative complication. This case demonstrates a successful implementation of directed thrombolysis, veno-arterial extracorporeal membrane oxygenation and multidisciplinary management in a case of postoperative saddle pulmonary embolus. PRÉCIS: We report a case of an endometrial cancer patient who sustained a massive postoperative pulmonary embolus and was successfully resuscitated using extracorporeal membrane oxygenation.

Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

ASCCP Colposcopy Standards: Colposcopy Quality Improvement Recommendations for the United States.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. The ASCCP Quality Improvement Working Group developed evidence-based guidelines to promote best practices and reduce errors in colposcopy and recommended indicators to measure colposcopy quality. MATERIALS AND METHODS: The working group performed a systematic review of existing major society and national guidelines and quality indicators. An initial list of potential quality indicators was developed and refined through successive iterative discussions, and draft quality indicators were proposed. The draft recommendations were then reviewed and commented on by the entire Colposcopy Standards Committee, posted online for public comment, and presented at the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered, additional adjustments made, and the final recommendations approved by the entire Task Force. RESULTS: Eleven quality indicators were selected spanning documentation, biopsy protocols, and time intervals between index screening tests and completion of diagnostic evaluation. CONCLUSIONS: The proposed quality indicators are intended to serve as a starting point for quality improvement in colposcopy at a time when colposcopy volume is decreasing and individual procedures are becoming technically more difficult to perform.

Systematic Review of International Colposcopy Quality Improvement Guidelines.

OBJECTIVES: The American Society for Colposcopy and Cervical Pathology Colposcopy Standards Committee organized multiple working groups to draft colposcopy standards for the United States. As part of this project, international quality assurance and improvement measures were examined. MATERIALS AND METHODS: The quality improvement working group performed a systematic review of the literature to collate international guidelines related to quality improvement. Source guidelines were collected using searches in Medline, Google Scholar, the International Federation of Cervical Pathology and Colposcopy Web site, other regional colposcopy group's Web sites, and communications with International Federation of Cervical Pathology and Colposcopy board of directors' members and other expert members of various national groups. Once identified, the sources were reviewed by multiple workgroup members for potential guideline materials. RESULTS: Fifty-six unique documents were identified, of which 18 met inclusion criteria and contributed data to the analysis. Information was abstracted and grouped by related subject. CONCLUSIONS: Wide variation exists in colposcopy guidance and quality indicators from regional and national colposcopy societies. Abstracted international guidelines are presented.

Wound Complication Rates After Staples or Suture for Midline Vertical Skin Closure in Obese Women: A Randomized Controlled Trial.

OBJECTIVE: To compare wound complication rates after skin closure with staples and subcuticular suture in obese gynecology patients undergoing laparotomy through a midline vertical incision. METHODS: In this randomized controlled trial, women with body mass indexes (BMIs) of 30 or greater undergoing surgery by a gynecologic oncologist through a midline vertical incision were randomized to skin closure with staples or subcuticular 4-0 monofilament suture. The primary outcome was the rate of wound complication, defined as the presence of a wound breakdown, or infection, within 8 weeks postoperatively. Secondary outcomes included operative time, Stony Brook scar cosmetic score, and patient satisfaction. A sample size of 162 was planned to detect a 50% reduction in wound complications. At planned interim review (n=82), there was no significant difference in primary outcome. RESULTS: Between 2013 and 2016, 163 women were analyzed, including 84 who received staples and 79 suture. Women who received staples were older (mean age 59 compared with 57 years), had lower mean BMI (37.3 compared with 38.9), and fewer benign indications for surgery (22 compared with 27). There were no differences in wound complication rates between staple compared with suture skin closure (28 [33%] compared with 25 [32%], relative risk 1.05, 95% confidence interval [CI] 0.68-1.64). Women with staples reported worse median cosmetic scores (four of five compared with five of five, P<.001), darker scar color (37 [49%] compared with 13 [18%], relative risk 2.69, 95% CI 1.57-4.63), and more skin marks (30 [40%] compared with three [4%], relative risk 9.47, 95% CI 3.02-29.65) compared with women with suture closure. There was no group difference regarding satisfaction with their scar. Stepwise multivariate analysis revealed BMI (odds ratio [OR] 1.13, 95% CI 1.07-1.20), maximum postoperative glucose (OR 1.01, 95% CI 1.00-1.01), and cigarette smoking (OR 4.96, 95% CI 1.32-18.71) were correlates of wound complication. CONCLUSION: Closure of midline vertical skin incisions with subcuticular suture does not reduce surgical site wound complications compared with staples in obese gynecology patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01977612.

In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel.

OBJECTIVE: To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. METHODS: Sexually active US women between 19 and 35years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8-12h after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8-12h after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. RESULTS: Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8-12h, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). CONCLUSIONS: This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection.

Preparedness of Ob/Gyn residents for fellowship training in gynecologic oncology.

Residency training in obstetrics and gynecology is being challenged by increasingly stringent regulations and decreased operative experience. We sought to determine the perception of preparedness of incoming gynecologic oncology fellows for advanced surgical training in gynecologic oncology. An online survey was sent to gynecologic oncologists involved in fellowship training in the United States. They were asked to evaluate their most recent incoming clinical fellows in the domains of professionalism, level of independence/graduated responsibility, psychomotor ability, clinical evaluation and management, and academia and scholarship using a standard Likert-style scale. The response rate among attending physicians was 40% (n = 105/260) and 61% (n = 28/46) for program directors. Of those who participated, 49% reported that their incoming fellows could not independently perform a hysterectomy, 59% reported that they could not independently perform 30 min of a major procedure, 40% reported that they could not control bleeding, 40% reported that they could not recognize anatomy and tissue planes, and 58% reported that they could not dissect tissue planes. Fellows lacked an understanding of pathophysiology, treatment recommendations, and the ability to identify and treat critically ill patients. In the academic domain, respondents agreed that fellows were deficient in the areas of protocol design (54%), statistical analysis (54%), and manuscript writing (65%). These results suggest that general Ob/Gyn residency is ineffective in preparing fellows for advanced training in gynecologic oncology and should prompt a revision of the goals and objectives of resident education to correct these deficiencies.