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Introduction: Patient-reported outcome measures (PROM) on quality of life (QOL) for early-stage floor of mouth carcinoma (FOM-CA) undergoing surgical resection and split-thickness skin graft (STSG) reconstruction have not been established. We have performed a cross-sectional QOL analysis of such patients to define functional postoperative outcomes. Methods: Patients with pathologic stage T1/T2 FOM-CA who underwent resection and STSG reconstruction at a tertiary academic cancer center reported outcomes with the University of Washington QOL (v4) questionnaire after at least 6 months since surgery. Results: Twenty-four out of 49 eligible patients completed questionnaires with a mean follow-up of 41 months (range: 6–88). Subsites of tumor involvement/resection included the following: (1) lateral FOM (L-FOM) (n = 17), (2) anterior FOM (A-FOM) (n = 4), and (3) alveolar ridge with FOM, all of whom underwent lateral marginal mandibulectomy (MM-FOM) (n = 3). All patients reported swallowing scores of 70 (“I cannot swallow certain solid foods”) or better. Ninety-six percent (23/24) reported speech of 70 (“difficulty saying some words, but I can be understood over the phone”) or better. A-FOM patients reported worse chewing than L-FOM patients (mean: 50.0 vs. 85.3; p = 0.01). All 4 A-FOM patients reported a low chewing score of 50 (“I can eat soft solids but cannot chew some foods”). Otherwise, there were no significant differences between subsite groups in swallowing, speech, or taste. Conclusion: STSG reconstructions for pathologic T1–T2 FOM-CA appear to result in acceptable PROM QOL outcomes with the exception of A-FOM tumors having worse chewing outcomes.

For human papilloma virus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset.Retrospective cohort study.National Cancer Database (NCDB).We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression.In therapeutic NDs (n = 1935), the following proportions of positive LNs were found: level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level: level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31;For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III.4.

OBJECTIVES/HYPOTHESIS For early-stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient-reported quality-of-life (QOL) outcomes following resection with primary closure (R-PC). STUDY DESIGN Retrospective review at an academic cancer center. METHODS Thirty-nine ESOTCCIS patients (Tis, T1, T2) who underwent R-PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW-QOL) at least 6 months since R-PC (mean = 2.39 years; range = 0.5-6.7 years). We compared UW-QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment. RESULTS ESOTCCIS patients who underwent R-PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P

Angle fractures are the most common among the mandibular fractures. History and physical examination are crucial in guiding time course and specifics of management. Computed tomography (CT) has become the gold standard for diagnosis of mandible fractures, offering advantages for both surgical planning and assessing dental involvement. Currently the use of a single monocortical plate with the Champy technique for osteosynthesis is used preferentially for noncomminuted fractures of the mandibular angle. Other load-sharing options for plating include strut plates, malleable plates, and geometric or 3D plates. Load-bearing options remain viable for comminuted fractures or other complex circumstances.

For human papillomavirus-associated oropharynx carcinoma treated with definitive surgery, we aimed to find predictors of adverse histopathology indicating the possible need for adjuvant therapy.Retrospective review.National Cancer Database.We analyzed 2347 eligible patients from 2010 to 2015. We evaluated (1) the ability of clinical nodal staging and extranodal extension designation per the AJCC, seventh edition (American Joint Committee on Cancer), to predict histopathology and (2) the likelihoods for adverse postsurgery histopathology by common clinical stages.Clinical nodal staging predicted pathologic nodal staging 65% of the time, with 24% (569/2347) being upstaged and 11% (251/2347) being downstaged. In patients with cN+ disease, clinical extranodal extension distinction had the following accuracy for pathologic extranodal extension: positive predictive value, 81% (88/109); negative predictive value, 73.1% (505/691); sensitivity, 32.1% (88/274); and specificity, 96.0% (505/526). Patients with cT1-2, N0-N2c, without clinical extranodal extension had the following proportions of pN2+ without pathologic extranodal extension (indicating consideration for adjuvant radiation): cN0, 11%; cN1, 31%; cN2a, 67% (8% downstaged); cN2b, 66% (6% downstaged); and cN2c, 35% (17% downstaged). From this group, patients had the following proportions of pathologic extranodal extension (indicating consideration for adjuvant chemoradiation): cN0, 6%; cN1, 20%; cN2a, 27%; cN2b, 28%; and cN2c, 48%.For human papillomavirus-associated oropharynx carcinoma, nodal clinical staging per the American Joint Committee on Cancer, seventh edition, predicts pathologic stage about two-thirds of the time, leading to up- and downstaging. Clinical extranodal extension assessment has low sensitivity and moderate predictive capability. With careful selection, definitive surgery can allow patients to often avoid adjuvant chemotherapy and sometimes avoid adjuvant radiation.

Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case–control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making $50,000/year [OR 2.47 (1.69–3.25); p interaction $50,000/year [1.28 (0.97–1.58); p interaction

With the planned scale-up of pre-exposure prophylaxis (PrEP) for HIV prevention among serodiscordant couples in resource-limited settings, gaining an understanding of what motivates serodiscordant couples to prevent HIV is critical. We conducted 44 semi-structured, in-depth individual or couple interviews with 63 participants (33 HIV-infected and 30 HIV-uninfected participants) enrolled in a prospective implementation study of oral antiretroviral-based prevention in Kisumu, Kenya. Transcripts were iteratively analysed using inductive content analysis. Findings point to the importance of maintaining the emotional and economic stability of the partnership and family as motivators in preventing HIV transmission. Female participants identified fear of blame or potential violence for transmitting HIV as a motivator. Furthermore, couples primarily held the HIV-infected individual responsible for HIV prevention, but also held women more accountable for the use of prevention methods such as condoms. These themes substantiate traditional gender norms but also reveal how dyadic interdependence challenges these norms. As programmes in resource-limited settings scale up PrEP access, they should simultaneously capitalise on HIV serodiscordant couples' motivations for HIV prevention and address gender norms so women do not find themselves unduly responsible for the prevention of HIV transmission.

Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB).We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method.Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non-ENE (HR, 4.9; P 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three-year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five-year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non-ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1-T2, with negative margins, pN0-N1, with ≤4 pathologic LNs, without ENE, and with20 LNs removed during neck dissection, the 3-year OS rates were 93% and 95%, respectively, and the 5-year OS rates were 91% and 95%, respectively.In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1-T2, pN0-N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS.4 Laryngoscope, 130:E423-E435, 2020.

Objective: Assess survival outcomes after surgery alone for p16-positive/human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) using the National Cancer Database (NCDB). Background: Survival outcomes for surgery alone for HPV+OPSCC without adjuvant radiation and chemotherapy are unclear. Adjuvant treatment may be unnecessary for some cases of HPV+OPSCC, given the reliance of current guidelines on extrapolations from studies of non-HPV associated OPSCC treatment. Methods: Overall survival (OS) was analyzed for 736 HPV+OPSCC patients who underwent surgery alone from 2010-2014. We studied available risk factors for death in the NCDB. Kaplan-Meir curves and crude and adjusted hazard ratios (HR) with Cox and Firth regression modeling were used. Staging was readjusted from the American Joint Committee on Cancer 7th edition to the 8th. Results: Most patients had T1/T2 (84.7%) and N0/N1 (74.7%) disease. OS after surgery alone for pathologic stage 1 disease at 3 and 5 years was 94% and 92%, respectively (p < 0.001). Stage 1 patients without adverse features (nodal involvement, lymphovascular invasion [LVI], positive margins) had equivalent survival to those with adverse features (p=0.7). Multivariate analysis controlling for pathologic T stage found the following independent risk factors for death after surgery alone: N2 versus N0 disease (HR 6.3, p=0.00002), microscopic ENE (HR 2.5, p=0.06) and macroscopic ENE (HR 4.8, p Conclusions: In this study, limited by the lack of data on smoking history, perineural invasion (PNI), recurrence, and disease-specific survival, HPV+OPSCC after surgery alone has a high overall survival, especially when stage 1 with pathologic N0 or N1 disease without ENE. Further studies of HPV+OPSCC patients who have refused adjuvant treatment with smoking, PNI, recurrence and disease-specific survival information are needed to evaluate the utility of surgery alone, especially for stage 1 cases with N1 disease. Citation Format: Mary Han, Gaelen B. Stanford-Moore, David W. Schoppy, William R. Ryan. Predictive factors for mortality after surgery alone for human papilloma virus-associated oropharynx squamous cell carcinoma: Analysis of the National Cancer Database [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A28.

Importance Many survivors of Ebola virus infection describe new-onset hearing loss after infection. The prevalence, severity, and pathophysiologic features of hearing loss in this population have not been well characterized. Objective To perform a systematic review of the current literature to characterize hearing loss in survivors of Ebola virus infection. Evidence Review This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Searches through PubMed, Embase, and Google Scholar were performed to include publications written in English from January 1, 1965, to October 1, 2018. Relevant vocabulary terms and key terms related to Ebola and hearing loss were used. Two investigators independently screened the eligible studies, extracted data, and assessed quality and risk of bias. Findings Of 127 publications reviewed, 15 met the criteria for inclusion; 3 were retrospective case-control studies (level of evidence, 3), and 12 were cross-sectional studies or case reports (level of evidence, 4). Studies included 1775 survivors of Ebola virus infection (993 female [55.9%]) and 363 uninfected controls (186 female [51.2%]) from the Democratic Republic of the Congo, Uganda, Guinea, Liberia, and Sierra Leone. The duration of follow-up ranged from 0 to 29 months (median, 5 months). Hearing loss was reported in 147 survivors of Ebola virus infection (8.3%). Among studies that compared survivors with controls, the reported odds ratios for hearing loss in survivors was 7.50 (95% CI, 3.91-14.39; range, 1.4-12.1). Including all studies, the odds ratio of hearing loss in survivors vs controls in countries where Ebola virus infection is endemic was 1.84 (95% CI, 1.10-3.08). Conclusions and Relevance Survivors of Ebola virus infection had higher rates of hearing loss than uninfected controls in regions where the infection is endemic. Further research with consistent objective methods and pure-tone audiometry may be needed to better characterize the hearing loss, understand its pathophysiologic features, and develop treatments.

Introduction : Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. Methods : We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Results : Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Conclusions : Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub-Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP. Keywords: pre-exposure prophylaxis; barriers; facilitators; heterosexual; HIV serodiscordant couples; Kenya. (Published: 12 December 2016) Citation: Patel RC et al. Journal of the International AIDS Society 2016, 19 :21134 http://www.jiasociety.org/index.php/jias/article/view/21134 | http://dx.doi.org/10.7448/IAS.19.1.21134

© 2015, Springer Science+Business Media New York (outside the USA). Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER+) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER+adenocarcinomas that had a high proliferative rate and other features consistent with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44High subpopulation was discovered, yet their tumor forming ability was far less than CD44Low cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER+ cancers. This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.

The evidence for the importance of the microenvironment in regulating cell behavior and maintaining tissue architecture is clear 1-3. Given this fact, it is essential to characterize the elaborate composition of tissues, which allows us to study the elaborate and dynamic interplay among the cellular and molecular constituents. Understanding these processes and determining how they coordinate to form and maintain tissues is a key question in biology. Yet, despite all that has been learned about the breast over the years, so much remains unknown about the orchestration and functional capabilities of these elements and how and why they sometimes lead to tumor formation. Although there is general agreement to the fundamental cellular composition of the breast, newer technologies and reagents permit exploring the cellular heterogeneity with unprecedented detail and clarity. Our goal here was to develop a fluorescence-assisted cell sorting (FACS) antibody panel and comprehensive gating strategy capable of resolving every major cell type in the breast, permitting their isolation to near purity (>99.5%). Using extensive immunostaining of reduction mammoplasty specimens to guide panel design, we developed a method capable of resolving 12 different epithelial and stromal cell populations, including several different epithelial fractions, myoepithelial cells, fibroblasts, adipocytes, leukocytes, pericytes, erythrocytes, adipose-derived mesenchymal stem cells, and both lymphatic and capillary endothelial cells. RNA from each population has been extracted and the transcriptional profiles will be determined by RNA sequencing to confirm each population's identity and lend insight to a number of biological questions. Functional studies are also ongoing, but we have to date successfully cultured each population (excluding blood cells) for several passages, using different media and ECM substrata. Future studies will be aimed at developing heterotypic culture models using these cells, but to also use our new knowledge and experience to similarly explore the heterogeneity of ductal carcinoma in situ (DCIS) and invasive breast cancers. We will present the development of this method and characterization to date of the sorted cell populations. 1. Bissell, M.J. & Hines, W.C. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17, 320-329 (2011). 2. Witkiewicz, A.K., Dasgupta, A., Sotgia, F., Mercier, I., Pestell, R.G., Sabel, M., Kleer, C.G., Brody, J.R. & Lisanti, M.P. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. The American journal of pathology 174, 2023-2034 (2009). 3. Ghajar, C.M., Meier, R. & Bissell, M.J. Quis custodiet ipsos custodies: who watches the watchmen? The American journal of pathology 174, 1996-1999 (2009). Citation Format: William C. Hines, Kate Thi, Maria Rojec, Gaelen Stanford-Moore, Mina J. Bissell. A cytometric atlas of the human breast: Comprehensive characterization reveals 12 distinct cell populations. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B86. doi:10.1158/1538-7445.CHTME14-B86