Background: Primary high-risk human papillomavirus (hr-HPV) testing of self-collected cervico-vaginal swabs could increase cervical cancer screening coverage, although triage strategies are needed to reduce unnecessary colposcopies. We evaluated the use of extended hr-HPV genotyping of self-collected samples for cervical cancer screening. Methods: We recruited women ages 25–65 years at two colposcopy clinics in North Carolina between November 2016 and January 2019, and obtained self-collected cervico-vaginal samples, provider-collected cervical samples, and cervical biopsies from all enrolled women. Self- and provider-collected samples were tested for 14 hr-HPV genotypes using the Onclarity Assay (Becton Dickinson). We calculated hr-HPV genotype–specific prevalence and assessed agreement between results in self- and provider-collected samples. We ranked the hr-HPV genotypes according to their positive predictive value (PPV) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN2+). Results: A total of 314 women participated (median age, 36 years); 85 women (27%) had CIN2+. More women tested positive for any hr-HPV on self-collected (76%) than on provider-collected samples (70%; P = 0.009) with type-specific agreement ranging from substantial to almost perfect. HPV-16 was the most common genotype in self-collected (27%) and provider-collected samples (20%), and HPV-16 prevalence was higher in self- than provider-collected samples (P < 0.001). In self- and provider-collected samples, HPV-16 had the highest PPV for CIN2+ detection. Conclusions: Overall sensitivity for CIN2+ detection was similar for both sample types, but the higher HPV-16 prevalence in self-collected samples could result in increased colposcopy referral rates. Impact: Additional molecular markers might be helpful to improve the triage of women who are hr-HPV positive on self-collected samples.

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca²⁺-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca²⁺-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca²⁺ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

Pulmonary diseases present a significant burden worldwide and lead to severe morbidity and mortality. Lung inflammation caused by interactions with either viruses, bacteria or fungi is a prominent characteristic of many pulmonary diseases. Tobacco smoke and E-cig use (“vaping”) are considered major risk factors in the development of pulmonary disease as well as worsening disease prognosis. However, at present, relatively little is known about the mechanistic actions by which smoking and vaping may worsen the disease. One theory suggests that long-term vaping leads to Ca²⁺ signaling dysregulation. Ca²⁺ is an important secondary messenger in signal transduction. Cellular Ca²⁺ concentrations are mediated by a complex series of pumps, channels, transporters and exchangers that are responsible for triggering various intracellular processes such as cell death, proliferation and secretion. In this review, we provide a detailed understating of the complex series of components that mediate Ca²⁺ signaling and how their dysfunction may result in pulmonary disease. Furthermore, we summarize the recent literature investigating the negative effects of smoking and vaping on pulmonary disease, cell toxicity and Ca²⁺ signaling. Finally, we summarize Ca²⁺-mediated pharmacological interventions that could potentially lead to novel treatments for pulmonary diseases.