ObjectiveCervical cancer screening usually requires use of a speculum to provide a clear view of the cervix. The speculum is one potential barrier to screening due to fear of pain, discomfort and embarrassment. The aim of this paper is to present and demonstrate the feasibility of a tampon-sized inserter and the POCkeT Colposcope, a miniature pen sized-colposcope, for comfortable, speculum-free and potentially self-colposcopy.Study designWe explored different designs using 3D computer-aided design (CAD) software and performed mechanical testing simulations on each. Designs were rapid prototyped and tested using a custom vaginal phantom across a range of vaginal pressures and uterine tilts to select an optimal design. Two final designs were tested with fifteen volunteers to assess cervix visualization, comfort and usability compared to the speculum and the optimal design, the curved-tip inserter, was selected for testing in volunteers.ResultsWe present a vaginal inserter as an alternative to the standard speculum for use with the POCkeT Colposcope. The device has a slim tubular body with a funnel-like curved tip measuring approximately 2.5 cm in diameter. The inserter has a channel through which a 2 megapixel (MP) mini camera with LED illumination fits to enable image capture. Mechanical finite element testing simulations with an applied pressure of 15 cm H2O indicated a high factor of safety (90.9) for the inserter. Testing of the device with a custom vaginal phantom, across a range of supine vaginal pressures and uterine tilts (retroverted, anteverted and sideverted), demonstrated image capture with a visual area comparable to the speculum for a normal/axial positioned uteri and significantly better than the speculum for anteverted and sideverted uteri (p<0.00001). Volunteer studies with self-insertion and physician-assisted cervix image capture showed adequate cervix visualization for 83% of patients. In addition, questionnaire responses from volunteers indicated a 92.3% overall preference for the inserter over the speculum and all indicated that the inserter was more comfortable than the speculum. The inserter provides a platform for self-cervical cancer screening and also enables acetic acid/Lugol’s iodine application and insertion of swabs for Pap smear sample collection.ConclusionThis study demonstrates the feasibility of an inserter and miniature-imaging device for comfortable cervical image capture of women with potential for synergistic HPV and Pap smear sample collection.

Fear of the speculum and feelings of vulnerability during the gynecologic exams are two of the biggest barriers to cervical cancer screening for women. To address these barriers, we have developed a novel, low-cost tool called the Callascope to reimagine the gynecological exam, enabling clinician and self-imaging of the cervix without the need for a speculum. The Callascope contains a 2 megapixel camera and contrast agent spray mechanism housed within a form factor designed to eliminate the need for a speculum during contrast agent administration and image capture. Preliminary bench testing for comparison of the Callascope camera to a $20,000 high-end colposcope demonstrated that the Callascope camera meets visual requirements for cervical imaging. Bench testing of the spray mechanism demonstrates that the contrast agent delivery enables satisfactory administration and cervix coverage. Clinical studies performed at Duke University Medical Center, Durham, USA and in Greater Accra Regional Hospital, Accra, Ghana assessed (1) the Callascope’s ability to visualize the cervix compared to the standard-of-care speculum exam, (2) the feasibility and willingness of women to use the Callascope for self-exams, and (3) the feasibility and willingness of clinicians and their patients to use the Callascope for clinician-based examinations. Cervix visualization was comparable between the Callascope and speculum (83% or 44/53 women vs. 100%) when performed by a clinician. Visualization was achieved in 95% (21/22) of women who used the Callascope for self-imaging. Post-exam surveys indicated that participants preferred the Callascope to a speculum-based exam. Our results indicate the Callascope is a viable option for clinician-based and self-exam speculum-free cervical imaging. Clinical study registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/record/ NCT00900575, Pan African Clinical Trial Registry (PACTR) https://www.pactr.org/ PACTR201905806116817.

Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100–200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called “BiCyclA”, was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.