Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study.

OBJECTIVES: While survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OPSCCs. METHODS: In this prospective exploratory cohort study, patients presenting to an Otolaryngology-Head and Neck Surgery clinic with unexplained signs or symptoms considered high-risk for HPV-positive OPSCC were recruited between March 2021-October 2022. Circulating TTMV-HPV DNA testing was performed, and results were shared with subjects and treating clinicians. Clinicians were surveyed regarding the perceived clinical utility of the test. RESULTS: Thirty-nine subjects were included. Most subjects were women (N = 23, 59 %), white (N = 32, 82 %) and never-smokers (N = 20, 51 %) with median age 60 years. Circulating TTMV-HPV DNA was detected in 2/39 subjects, both subsequently diagnosed with HPV-positive OPSCC. Both were white men aged 70-80 years with a neck mass. One subject with undetectable TTMV-HPV DNA was also diagnosed with HPV-positive OPSCC through excisional neck mass biopsy. Other eventual diagnoses included 3 HPV-negative head and neck squamous cell carcinomas and 4 other malignancies. Testing was perceived as helpful in clinical decision-making for 26/38 (68 %) subjects, and useful for similar future patients for 32/37 (86 %) subjects. CONCLUSION: Circulating TTMV-HPV DNA testing is feasible and holds potential as a diagnostic aid for HPV-positive OPSCC alongside standard clinical workup. Clinicians should be cognizant of its limitations, as a negative test does not necessarily indicate the absence of disease. Further studies to evaluate its utility are warranted.

Global Health 101.

Global health is an evolving field that has been broadly defined as the promotion of health for all through transnational collaboration and research. It centers on the concepts of equity and collaboration. The focus of global health has recently undergone a major shift toward emphasizing the importance of a systems-based approach to healthcare delivery, which considers not only the target disease but also the many contextual factors, influencing the ability to deliver care equitably to a population to reduce the burden of any particular disease. Thus, an important global health delivery framework has been established to outline this inter- and multi-disciplinary systems-based to address major global health issues and improve health for all globally. The practice of global health, whether in research or in active intervention, necessitates guiding principles to ensure ethical conduct in the transnational partnerships and efforts to advance the field. With the introduction of the United Nations' Sustainable Development Goals in 2015, there has been a major shift in response to epidemiologic transition to focus on reducing the burden of noncommunicable diseases, including cancer, which disproportionately impact low-to-middle income countries. This is true for colorectal cancer, with care challenged by significant gaps in screening, early detection, and referral systems.

Colonoscopy Needs for Implementation of a Colorectal Cancer Screening Program in Ukraine.

BACKGROUND: In Ukraine, there is no established colorectal cancer screening program. We aimed to project the number of screening colonoscopies needed for implementation of various CRC screening strategies in Ukraine. METHODS: We modified a previously developed Markov microsimulation model to reflect the natural history of adenoma and CRC progression among average-risk 50-74-year-olds. We simulated colonoscopies needed for the following screening strategies: no screening, fecal occult blood test yearly, FOBT yearly with flexible sigmoidoscopy every 5 years, FS every 5 years, fecal immunohistochemistry test (FIT) yearly, or colonoscopy every 10 years. Assuming 80% screening adherence, we estimated colonoscopies required at 1 and 5 years depending on the implementation rate. In one-way sensitivity analyses, we varied implementation rate, screening adherence, sensitivity, and specificity. RESULTS: Assuming an 80% screening adherence and complete implementation (100%), besides a no screening strategy, the fewest screening colonoscopies are needed with an FOBT program, requiring on average 6,600 and 26,800 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. The most screening colonoscopies are required with a colonoscopy program, requiring on average 76,600 and 101,000 colonoscopies per 100,000 persons at 1 and 5 years post-implementation, respectively. In sensitivity analyses, the biggest driver of number of colonoscopies needed was screening adherence. CONCLUSIONS: The number of colonoscopies needed and therefore the potential strain on the healthcare system vary substantially by screening test. These findings can provide valuable information for stakeholders on equipment needs when implementing a national screening program in Ukraine.

Association of Outpatient Oral Macrolide Use With Sensorineural Hearing Loss in Children, Adolescents, and Young Adults.

Importance: Prior publications have reported the sporadic development of sensorineural hearing loss (SNHL) after intravenous or high-dose macrolide therapy for adults with comorbid conditions, but investigations of the auditory effect of oral outpatient dosing for children, adolescents, and young adults have been limited. Objective: To determine whether broad-based outpatient use of oral macrolide therapy is associated with increased risk of pediatric SNHL through nationally representative analyses. Design, Setting, and Participants: A retrospective case-control study of 875 matched pairs of children, adolescents, and young adults was performed, matching on age, sex, and the time elapsed since prescription date. All eligible pediatric patients were included, with matched control participants from the TRICARE US military health insurance system who were evaluated between October 1, 2009, and September 30, 2014. Exposures: Oral outpatient macrolide treatment compared with penicillin use among pediatric patients. Main Outcomes and Measures: The clinical outcome of interest was SNHL in children, adolescents, and young adults. Multivariable conditional logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders. Four time frames between exposure and diagnosis were additionally assessed. Results: There were 875 eligible matched pairs of children, adolescents, and young adults included. The mean (SD) age of the participants was 5.7 (4.9) years; 1082 participants were male (62%), 58 were Asian (3%), 254 were Black (15%), 1152 were White (66%), and 286 were of Native American and other (no further breakdown was available in the TRICARE database) race and ethnicity (16%). In multivariable analysis, participants who had SNHL had increased odds of having received a macrolide prescription compared with a penicillin prescription when all time frames from exposure were included (adjusted odds ratio, 1.31; 95% CI, 1.05-1.64). There were significantly higher odds of macrolide exposure than penicillin exposure when diagnosis and testing occurred more than 180 days after antibiotic exposure (adjusted odds ratio, 1.79; 95% CI, 1.23-2.60). Conclusions and Relevance: In this case-control study of a nationally representative patient population, findings suggest that children, adolescents, and young adults with SNHL had increased odds of outpatient oral macrolide use compared with penicillin use, particularly when having received a diagnosis more than 180 days after exposure. Further study of the association of macrolides with SNHL in children, adolescents, and young adults is warranted.

American Head and Neck Society Endocrine Surgery Section and International Thyroid Oncology Group consensus statement on mutational testing in thyroid cancer: Defining advanced thyroid cancer and its targeted treatment.

BACKGROUND: The development of systemic treatment options leveraging the molecular landscape of advanced thyroid cancer is a burgeoning field. This is a multidisciplinary evidence-based statement on the definition of advanced thyroid cancer and its targeted systemic treatment. METHODS: An expert panel was assembled, a literature review was conducted, and best practice statements were developed. The modified Delphi method was applied to assess the degree of consensus for the statements developed by the author panel. RESULTS: A review of the current understanding of thyroid oncogenesis at a molecular level is presented and characteristics of advanced thyroid cancer are defined. Twenty statements in topics including the multidisciplinary management, molecular evaluation, and targeted systemic treatment of advanced thyroid cancer are provided. CONCLUSIONS: With the growth in targeted treatment options for thyroid cancer, a consensus definition of advanced disease and statements regarding the utility of molecular testing and available targeted systemic therapy is warranted.

Promoting Female Leadership in Academic Surgery: Disrupting Systemic Gender Bias.

Gender bias is a pervasive issue in academic surgery and is characterized by familiar patterns previously described in the business world. In this article, the authors illuminate gender bias patterns in academic surgery identified in prior in-depth interviews with female surgical department chairs across the United States. The 4 main gender bias patterns drawn from the business world and illuminated with data from the interviews are (1) prove-it-again, (2) tightrope or double-blind dilemma, (3) maternity wall or benevolent bias, and (4) tug-of-war. The authors propose steps to disrupt systemic gender bias issues recognized in the academic surgery community. The proposed steps are informed by guidance from surgical diversity task forces, by existing literature, and by the authors' own experiences in the field. The steps are divided into 3 main categories: education, structured mentorship, and transparency. The proposed changes include improving training and recognition of unconscious bias, establishing level-appropriate and deliberate mentorship across all stages of training and practice, standardizing promotional requirements, and eliminating outdated standards that contribute to the gender pay gap. Although this article addresses gender bias in academic surgery, the proposed steps toward change can promote equity across the surgical community as a whole and extend to other underrepresented groups in the field.