Major determining factors for survival of patients with oral, oropharyngeal, and esophageal cancer are early detection, the quality of surgical margins, and the contemporaneous detection of residual tumor. Intuitively, the exposed location at the epithelial surface qualifies these tumor types for utilization of visual aids to assist in discriminating tumor from healthy surrounding tissue. Here, we explored the DNA repair enzyme PARP1 as imaging biomarker and conducted optical imaging in animal models, human tissues and as part of a first-in-human clinical trial. Our data suggests that PARP1 is a quantitative biomarker for oral, oropharyngeal, and esophageal cancer and can be visualized with PARPi-FL, a fluorescently labeled small molecule contrast agent for topical or intravenous delivery. We show feasibility of PARPi-FL-assisted tumor detection in esophageal cancer, oropharyngeal and oral cancer. We developed a contemporaneous PARPi-FL topical staining protocol for human biospecimens. Using fresh oral cancer tissues within 25 min of biopsy, tumor and margin samples were correctly identified with >95% sensitivity and specificity without terminal processing. PARPi-FL imaging can be integrated into clinical workflows, potentially providing instantaneous assessment of the presence or absence of microscopic disease at the surgical margin. Additionally, we showed first-in-human PARPi-FL imaging in oral cancer. In aggregate, our preclinical and clinical studies have the unifying goal of verifying the clinical value of PARPi-FL-based optical imaging for early detection and intraoperative margin assignment.
Oral cancer is one of the most common cancers globally. Survival rates for patients are directly correlated with stage of diagnosis; despite this knowledge, 60% of individuals are presenting with late-stage disease. Currently, the initial evaluation of a questionable lesion is performed by a conventional visual examination with white light. If a lesion is deemed suspicious, a biopsy is taken for diagnosis. However, not all lesions present suspicious under visual white light examination, and there is limited specificity in differentiating between benign and malignant transformations. Several vital dyes, light-based detection systems, and cytology evaluation methods have been formulated to aid in the visualization process, but their lack of specific biomarkers resulted in high false-positive rates and thus limits their reliability as screening and guidance tools. In this review, we will analyze the current methodologies and demonstrate the need for specific intraoral imaging agents to aid in screening and diagnosis to identify patients earlier. Several novel molecular imaging agents will be presented as, by result of their molecular targeting, they aim to have high specificity for tumor pathways and can support in identifying dysplastic/cancerous lesions and guiding visualization of biopsy sites. Imaging agents that are easy to use, inexpensive, noninvasive, and specific can be utilized to increase the number of patients who are screened and monitored in a variety of different environments, with the ultimate goal of increasing early detection.
Breast cancer is the most common type of malignant growth in women. Early detection of breast cancer, as well as the identification of possible metastatic spread poses a significant challenge because of the structural and genetic heterogeneity that occurs during the progression of the disease. Currently, mammographies, biopsies and MRI scans are the standard of care techniques used for breast cancer diagnosis, all of which have their individual shortfalls, especially when it comes to discriminating tumors and benign growths. With this in mind, we have developed a non-invasive optoacoustic imaging strategy that targets the acidic environment of breast cancer. A pH low insertion peptide (pHLIP) was conjugated to the dark quencher QC1, yielding a non-fluorescent sonophore with high extinction coefficient in the near infrared that increases signal as a function of increasing amounts of membrane insertion. In an orthotopic murine breast cancer model, pHLIP-targeted optoacoustic imaging allowed us to differentiate between healthy and breast cancer tissues with high signal/noise ratios. In vivo , the sonophore QC1-pHLIP could detect malignancies at higher contrast than its fluorescent analog ICG-pHLIP, which was developed for fluorescence-guided surgical applications. PHLIP-type optoacoustic imaging agents in clinical settings are attractive due to their ability to target breast cancer and a wide variety of other malignant growths for diagnostic purposes. Intuitively, these agents could also be used for visualization during surgery.
PURPOSE Although rates of sexually transmitted infections (STIs) and human papillomavirus (HPV)-related head and neck cancers associated with oral sex are increasing, less than 10% of youths report using protection. This study aims to assess youths' knowledge and perceptions of oral sex risk and barriers to protection use. METHODSOur study uses MyVoice, a national text message poll of youths aged 14-24 years. Four open-ended probes were fielded to 1,215 youths in March 2019. Qualitative data were analyzed using thematic analysis and quantitative data were summarized with descriptive statistics. RESULTSNine hundred and nine youths responded to the survey (relative risk [RR] = 74.8%). Youths' responses regarding why protection is frequently not used centered around: lack of education (22.4%), no perceived STI risk (19.8%), decreased pleasure (19.3%), and no pregnancy risk (15.7%). Youths believed that comprehensive education (53.7%), normalization in popular culture and media (19.1%), increased access to protection (15%), and improved protection options (10.5%) would increase protection use during oral sex.CONCLUSION Youths demonstrated limited knowledge of the risks of oral sex, dissatisfaction with current protection options, and a need for normalization in popular culture. Programs developed with youths in mind may be able to successfully increase protection use and decrease rates of STI transmission and oral sex-related HPV head and neck cancer.
Social distancing is an important public health recommendation that has been implemented to reduce the spread of COVID-19. Infections are rising among younger populations, but relatively little is known about youth social distancing behavior. Our qualitative study aims to examine youth engagement with social distancing and elucidate the reasons why guidelines are followed and broken. Members of the national MyVoice Text Message Cohort (aged 14–24) were surveyed from April 24 to April 30, 2020, through an open-ended text message poll. Responses were inductively coded and analyzed with descriptive statistics. Of the 944 youth who responded (response rate = 81.2%), 95% self-reported social distancing. However, 62% recalled instances of themselves or others breaking the guidelines and 19% expressed misconceptions about the rules. Notably, 14% of youth said they would encourage their friends to social distance by telling them it will accelerate a return to normal life. Feelings of social isolation were the most frequently cited (55%) negative impact of social distancing. Overall, responses from youth indicate significant variation in the interpretation of social distancing guidelines. Public health communications may need to address several critical misconceptions which impact the social distancing behaviors of youth. Further, safe methods for youth to interact with peers during periods of social distancing are necessary to prevent mental health impacts and to ensure adherence to social distancing guidelines.
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