Browsing by Author "Schmeler, Kathleen M."
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Item A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings(Royal Society of Chemisty, 2023) Smith, Chelsey A.; Chang, Megan M.; Kundrod, Kathryn A.; Novak, Emilie N.; Parra, Sonia G.; López, Leticia; Mavume, Celda; Lorenzoni, Cesaltina; Maza, Mauricio; Salcedo, Mila P.; Carns, Jennifer L.; Baker, Ellen; Montealegre, Jane; Scheurer, Michael; Castle, Philip E.; Schmeler, Kathleen M.; Richards-Kortum, Rebecca R.Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay (“Xpert”), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.Item A mobile-phone based high-resolution microendoscope to image cervical precancer(Public Library of Science, 2019) Grant, Benjamin D.; Quang, Timothy; Possati-Resende, Júlio César; Scapulatempo-Neto, Cristovam; Matsushita, Graziela de Macedo; Mauad, Edmundo Carvalho; Stoler, Mark H.; Castle, Philip E.; Fregnani, José Humberto Tavares Guerreiro; Schmeler, Kathleen M.; Richards-Kortum, RebeccaNearly 90% of cervical cancer cases and deaths occur in low- and middle-income countries that lack comprehensive national HPV immunization and cervical cancer screening programs. In these settings, it is difficult to implement screening programs due to a lack of infrastructure and shortage of trained personnel. Screening programs based on visual inspection with acetic acid (VIA) have been successfully implemented in some low-resource settings. However, VIA has poor specificity and up to 90% of patients receiving treatment based on a positive VIA exam are over-treated. A number of studies have suggested that high-resolution cervical imaging to visualize nuclear morphology in vivo can improve specificity by better distinguishing precancerous and benign lesions. To enable high-resolution imaging in low-resource settings, we developed a portable, low-cost, high-resolution microendoscope that uses a mobile phone to detect and display images of cervical epithelium in vivo with subcellular resolution. The device was fabricated for less than $2,000 using commercially available optical components including filters, an LED and triplet lenses assembled in a 3D-printed opto-mechanical mount. We show that the mobile high-resolution microendoscope achieves similar resolution and signal-to-background ratio as previously reported high-resolution microendoscope systems using traditional cameras and computers to detect and display images. Finally, we demonstrate the ability of the mobile high-resolution microendoscope to image normal and precancerous squamous epithelium of the cervix in vivo in a gynecological referral clinic in Barretos, Brazil.Item American Society of Clinical Oncology (ASCO) Cervical Cancer Prevention Program: A Hands-On Training Course in Nepal(ASCO, 2021) Phoolcharoen, Natacha; Kremzier, Megan; Eaton, Vanessa; Sarchet, Vanessa; Acharya, Sandhya Chapagain; Shrestha, Eliza; Carns, Jennifer; Baker, Ellen; Varon, Melissa Lopez; Karmacharya, Saujanya; Aryal, Binod; Richards-Kortum, Rebecca; Salcedo, Mila Pontremoli; Schmeler, Kathleen M.; Pariyar, JitendraCervical cancer is the leading cause of death among women in Nepal. The American Society of Clinical Oncology (ASCO) and The University of Texas MD Anderson Cancer Center collaborated with international and local experts to hold a cervical cancer prevention course in Nepal in November 2019. The course included didactic lectures and a hands-on workshop. The didactic lectures included the epidemiology of cervical cancer globally and locally, cervical cancer screening guidelines, human papillomavirus vaccination, colposcopy and visual inspection with acetic acid (VIA), cervical dysplasia, and cervical cancer treatment. The hands-on workshop consisted of four stations: (1) VIA; (2) colposcopy, cervical biopsy, and endocervical curettage; (3) thermal ablation; and (4) loop electrosurgical excision procedure (LEEP). A train-the-trainer model short course was held by the international faculty to assist six local faculty to become familiar with the instruments, procedures, and models used in the hands-on training stations. Forty-two people (84% gynecologist, 8% radiation oncologist, and 8% other) attended the course. Following the course, the international faculty visited the regional hospitals for additional educational activities. Increased knowledge in cervical cancer screening guidelines and ability in performing VIA, colposcopy and cervical biopsy, thermal ablation, and LEEP were reported by 89%, 84%, 84%, 87%, and 84% of participants, respectively, from the postcourse on-site evaluations. From the 6-month follow-up survey, all respondents reported that they had made practice changes based on what they learned in the course and had implemented or tried to implement the cervical cancer screening guidelines presented at the course. In conclusion, the course evaluations suggested an improvement in participants' ability to perform cervical cancer screening and diagnostic procedures and reported the changes in practices after training.Item Building local capacity for cervical cancer prevention in low resource settings: Changing strategy during the COVID-19 pandemic(ISGH, 2021) Salcedo, Mila P.; Varon, Melissa L.; Phoolcharoen, Natacha; Osman, Nafissa; David, Ernestina; Rangeiro, Ricardina; Changule, Dercia; Andrade, Viviane; Neves, Andrea; Doughtie, Kathleen M.; Carns, Jennifer; Lorenzoni, Cesaltina; Baker, Ellen; Schmeler, Kathleen M.In low- and middle-income countries (LMIC), where the great majority of cervical cancer cases occur, there is a shortage of health care providers trained to diagnose and treat pre-invasive cervical disease. The cervical cancer regional incidence and mortality rates are highest in sub-Saharan Africa and South-Eastern Asia [1]. In many resource-constrained regions, the shortage of trained providers limits the scale-up of quality cervical cancer screening, diagnosis and treatment services. In Mozambique, cervical cancer is the primary cause of cancer and cancer-related deaths among women [2,3]. Since 2016 we have provided in-person support and training to gynecologists and nurses in Mozambique. Cervical cancer prevention training, included teaching skills of colposcopy, cervical biopsy and loop electrosurgical excision procedure (LEEP) [4] Completion of hands-on training was followed by patient care with the trainers in local clinics. Participation in monthly Project ECHO (Extension of Community Healthcare Outcomes) telementoring sessions was encouraged to reinforce and amplify knowledge and skills. Since March 2020 travel has been restricted due to coronavirus disease (COVID-19). We have therefore adapted the way we deliver this training and provide support to colleagues in Mozambique so that capacity building efforts continue.Item Development of a multimodal mobile colposcope for real-time cervical cancer detection(Optica Publishing Group, 2022) Coole, Jackson B.; Brenes, David; Possati-Resende, Júlio César; Antoniazzi, Márcio; Fonseca, Bruno de Oliveira; Maker, Yajur; Kortum, Alex; Vohra, Imran S.; Schwarz, Richard A.; Carns, Jennifer; Souza, Karen Cristina Borba; Santana, Iara Viana Vidigal; Kreitchmann, Regis; Salcedo, Mila P.; Salcedo, Mila P.; Ramanujam, Nirmala; Schmeler, Kathleen M.; Richards-Kortum, RebeccaCervical cancer remains a leading cause of cancer death among women in low-and middle-income countries. Globally, cervical cancer prevention programs are hampered by a lack of resources, infrastructure, and personnel. We describe a multimodal mobile colposcope (MMC) designed to diagnose precancerous cervical lesions at the point-of-care without the need for biopsy. The MMC integrates two complementary imaging systems: 1) a commercially available colposcope and 2) a high speed, high-resolution, fiber-optic microendoscope (HRME). Combining these two image modalities allows, for the first time, the ability to locate suspicious cervical lesions using widefield imaging and then to obtain co-registered high-resolution images across an entire lesion. The MMC overcomes limitations of high-resolution imaging alone; widefield imaging can be used to guide the placement of the high-resolution imaging probe at clinically suspicious regions and co-registered, mosaicked high-resolution images effectively increase the field of view of high-resolution imaging. Representative data collected from patients referred for colposcopy at Barretos Cancer Hospital in Brazil, including 22,800 high resolution images and 9,900 colposcope images, illustrate the ability of the MMC to identify abnormal cervical regions, image suspicious areas with subcellular resolution, and distinguish between high-grade and low-grade dysplasia.Item Low-cost, high-resolution imaging for detecting cervical precancer in medically-underserved areas of Texas(Elsevier, 2019) Parra, Sonia G.; Rodriguez, Ana M.; Cherry, Katelin D.; Schwarz, Richard A.; Gowen, Rose M.; Guerra, Laura B.; Milbourne, Andrea M.; Toscano, Paul A.; Fisher-Hoch, Susan P.; Schmeler, Kathleen M.; Richards-Kortum, Rebecca R.Objective: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. Methods: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. Results: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). Conclusions: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.Item Sample-to-answer, extraction-free, real-time RT-LAMP test for SARS-CoV-2 in nasopharyngeal, nasal, and saliva samples: Implications and use for surveillance testing(Public Library of Science, 2022) Kundrod, Kathryn A.; Natoli, Mary E.; Chang, Megan M.; Smith, Chelsey A.; Paul, Sai; Ogoe, Dereq; Goh, Christopher; Santhanaraj, Akshaya; Price, Anthony; Eldin, Karen W.; Patel, Keyur P.; Baker, Ellen; Schmeler, Kathleen M.; Richards-Kortum, RebeccaThe global COVID-19 pandemic has highlighted the need for rapid, accurate and accessible nucleic acid tests to enable timely identification of infected individuals. We optimized a sample-to-answer nucleic acid test for SARS-CoV-2 that provides results in <1 hour using inexpensive and readily available reagents. The test workflow includes a simple lysis and viral inactivation protocol followed by direct isothermal amplification of viral RNA using RT-LAMP. The assay was validated using two different instruments, a portable isothermal fluorimeter and a standard thermocycler. Results of the RT-LAMP assay were compared to traditional RT-qPCR for nasopharyngeal swabs, nasal swabs, and saliva collected from a cohort of patients hospitalized due to COVID-19. For all three sample types, positive agreement with RT-LAMP performed using the isothermal fluorimeter was 100% for samples with Ct <30 and 69–91% for samples with Ct <40. Following validation, the test was successfully scaled to test the saliva of up to 400 asymptomatic individuals per day as part of the campus surveillance program at Rice University. Successful development, validation, and scaling of this sample-to-answer, extraction-free real-time RT-LAMP test for SARS-CoV-2 adds a highly adaptable tool to efforts to control the COVID-19 pandemic, and can inform test development strategies for future infectious disease threats.Item Toward development of a large field-of-view cancer screening patch (CASP) to detect cervical intraepithelial neoplasia(Optical Society of America, 2019) Gawedzinski, John; Schmeler, Kathleen M.; Milbourne, Andrea; Ramalingam, Preetha; Moghaddam, Parnian A.; Richards-Kortum, Rebecca; Richards-Kortum, Rebecca; Tkaczyk, Tomasz S.; Tkaczyk, Tomasz S.Cervical cancers are primarily diagnosed via colposcopy, in which the tissue is visually assessed by a clinician for abnormalities, followed by directed biopsies and histologic analysis of excised tissue. Optical biopsy technologies offer a less invasive method of imaging such that subcellular features can be resolved without removing tissue. These techniques, however, are limited in field-of-view by the distal end of the probe. We present a prototype that incorporates a rigid, machinable waveguide that is in direct contact with a fluorescently-labeled sample paired with a scanning fluorescent microscope. The system is capable of imaging large areas of tissue without the need to re-position the tissue-probe interface. A mosaicing algorithm was developed to quantify scanning shifts and stitch neighboring frames together to increase the field-of-view. Our prototype can yield a maximum axial resolution of <5 µm for individual frames and can produce mosaiced images with a field-of-view greater than 15 mm x 15 mm without sacrificing resolution. We validated the system with a 1951 USAF resolution target, fluorescent in vitro standards, and a patient study where ex vivo conization samples of squamous cervical epithelium were imaged. The results of the patient study indicate that architectural features of subcellular components could be detected and differentiated between normal tissue and precancerous lesions.