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2022 ◽  
Author(s):  
Andrew Brouwer ◽  
Lora P Campredon ◽  
Heather M Walline ◽  
Brittany M Marinelli ◽  
Christine M Goudsmit ◽  
...  

We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older-adult participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample. Samples were tested for 18 HPV genotypes using polymerase chain reaction (PCR) MassArray. Participants filled out sociodemographic and behavioral questionnaires. Prevalence ratios for HPV oral or cervicogenital prevalence by predictor variables were estimated in univariable log-binomial models. Analysis was conducted 2018-20. In the full cohort, baseline oral HPV prevalence was 10.0% for any detected genotype (among the 338 valid oral tests at baseline) and 6.5% for high-risk types, and cervicogenital prevalence was 20.0% and 10.8%, respectively (among the 130 first valid cervicogenital tests). Oral HPV prevalence did not vary by sex, with 10.5% of women and 9.0% of men having an infection. We found a high prevalence of oral and cervicogenital HPV infection among those reporting no recent sexual partners compared to those with a single recent sexual partner, but prevalence increased with the number of recent partners for most sexual behaviors. We observed an ecological fallacy masking the direction of impact of vaccination on HPV prevalence in the full cohort compared to the college-aged and older-adult populations considered separately. Substance use was not significantly associated with oral or cervicogenital HPV infection. Many studies report substantially higher oral HPV infection prevalence in men than in women. That difference may not be uniform across populations in the US.


2022 ◽  
Author(s):  
Aitor Nogales ◽  
John Steel ◽  
Wen-Chun Liu ◽  
Anice C Lowen ◽  
Laura Rodriguez ◽  
...  

Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year old healthy and non-pregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The United States (U.S.) licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain.


BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e056502
Author(s):  
Andrew F Brouwer ◽  
Lora P Campredon ◽  
Heather M Walline ◽  
Brittany M Marinelli ◽  
Christine M Goudsmit ◽  
...  

ObjectivesThe Michigan HPV and Oropharyngeal Cancer study aimed to evaluate patterns of oral and cervicogenital human papillomavirus (HPV) infection prevalence, incidence, and clearance as well as their relationship to sexual behaviours.DesignCohortSettingGeneral public in and around Ann Arbor, Michigan.Participants394 college-age and older-adult participants of both sexes provided oral samples, and 325 completed at least 2 visits. 130 who provided a cervicogenital samples, and 127 completed at least 2 visits.OutcomesIncidence and clearance rates as well as HRs for oral and cervicogenital HPV.ResultsOral HPV infections were transient, with only 16% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 46 days (95% CI 37 to 58). In contrast, cervicogenital infections were more persistent, with 56% of genotypes persisting to the next visit. The mean time to clearance of a genotype was 87 days (95% CI 74 to 102). HPV vaccination was associated with reduced incidence of cervicogenital HPV infection (HR 0.63; 95% CI 0.47 to 0.83) but not oral HPV infection. Incidence of oral HPV infection was associated with 2+ recent deep kissing partners (HR 2.00; 95% CI 1.13 to 3.56). Incidence of both oral (HR: 1.70; 95% CI 1.08 to 2.68) and cervicogenital (HR 2.46; 95% CI 1.69 to 3.59) was associated with 2+ recent sexual partners.ConclusionsDetection of oral HPV was highly transient, but incidence was associated with recent deep kissing and sexual partners. Detection of cervicogenital HPV was more persistent, and incidence was positively associated with recent sexual partners and negatively associated with HPV vaccination.


Blood ◽  
2021 ◽  
Author(s):  
Eliza A. Hawkes ◽  
Allison Barraclough ◽  
Laurie H. Sehn

DLBCL, the most common lymphoma subtype, is localized in 25-30% of patients. Prognosis in patients with limited-stage DLBCL (LS-DLBCL) is excellent with 10-year overall survival of at least 70-80%. Improved insights into the disease biology, the availability of positron-emission tomography (PET) scans and recent dedicated clinical trials within this unique population, have led to evolving treatment paradigms. However, no standard definition of LS-DLBCL exists, and while generally defined as Ann Arbor stages I-II disease with largest mass size <10cm in diameter, variations across studies cause challenges in interpretation. Similar to advanced-stage disease, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) immunochemotherapy forms the basis of treatment, with combined modality therapy including 3 cycles of systemic treatment and involved-site radiation therapy being a predominant historical standard. Yet the well-described continuous risk of relapse beyond 5 years and established late complications of radiotherapy have challenged previous strategies. More rigorous baseline staging and response assessment with PET may improve decision making. Recent clinical studies have focused on minimizing toxicities while maximizing disease outcomes using strategies such as abbreviated immunochemotherapy alone and PET-adapted radiotherapy delivery. This comprehensive review provides an update of recent literature with recommendations for integration into clinical practice for LS-DLBCL patients.


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