A central chaperone-like role for 14-3-3 proteins in human cells.

14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients and act as central hubs of signaling networks. However, how 14-3-3 paralogs differ in specificity and how they regulate client protein function are not known for most clients. Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. The loss of 14-3-3 binding leads to the coalescence of a large fraction of clients into discrete foci in a client-specific manner, suggesting a central chaperone-like function for 14-3-3 proteins. Congruently, the engraftment of 14-3-3 binding motifs to nonclients can suppress their aggregation or phase separation. Finally, we show that 14-3-3s negatively regulate the localization of the RNA-binding protein SAMD4A to cytoplasmic granules and inhibit its activity as a translational repressor. Our work suggests that 14-3-3s have a more prominent role as chaperone-like molecules than previously thought.

PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.

Poly(ADP-ribose) polymerase 1 (PARP1) is one of the first responders to DNA damage and plays crucial roles in recruiting DNA repair proteins through its activity - poly(ADP-ribosyl)ation (PARylation). The enrichment of DNA repair proteins at sites of DNA damage has been described as the formation of a biomolecular condensate. However, it remains unclear how exactly PARP1 and PARylation contribute to the formation and organization of DNA repair condensates. Using recombinant human single-strand repair proteins in vitro, we find that PARP1 readily forms viscous biomolecular condensates in a DNA-dependent manner and that this depends on its three zinc finger (ZnF) domains. PARylation enhances PARP1 condensation in a PAR chain length-dependent manner and increases the internal dynamics of PARP1 condensates. DNA and single-strand break repair proteins XRCC1, LigIII, Polß, and FUS partition in PARP1 condensates, although in different patterns. While Polß and FUS are both homogeneously mixed within PARP1 condensates, FUS enrichment is greatly enhanced upon PARylation whereas Polß partitioning is not. XRCC1 and LigIII display an inhomogeneous organization within PARP1 condensates; their enrichment in these multiphase condensates is enhanced by PARylation. Functionally, PARP1 condensates concentrate short DNA fragments, which correlates with PARP1 clusters compacting long DNA and bridging DNA ends. Furthermore, the presence of PARP1 condensates significantly promotes DNA ligation upon PARylation. These findings provide insight into how PARP1 condensation and PARylation regulate the assembly and biochemical activities of DNA repair factors, which may inform on how PARPs function in DNA repair foci and other PAR-driven condensates in cells.

Adjuvant therapy improves survival in pT4aN0 oral cavity squamous cell carcinoma with bone invasion.

OBJECTIVE: The prognostic significance of bone invasion in oral cavity squamous cell carcinoma (OCSCC) after accounting for tumor size, nodal spread, and surgical margins is controversial. The aim of this study is to determine whether patients with pT4aN0 oral cavity squamous cell carcinoma with bone invasion have improved overall and disease-free survival with adjuvant treatment. METHODS: We conducted a retrospective review of medical records from 64 patients with stage pT4aN0 due to mandibular involvement who underwent surgery from 2000 to 2020. Kaplan-Meier analysis compared disease-free survival and overall survival between groups who underwent surgery only versus surgery and adjuvant therapy. The prognostic impact of adjuvant therapy was assessed using multivariate analysis and reported as hazard ratios. RESULTS: There were no statistically significant differences in clinicopathologic features or mean follow-up between patients who received surgery only and patients who received surgery with RT/CCRT (radiotherapy/concurrent chemoradiation therapy). 5-year disease-free (42.5% versus 65.9%, p = 0.02) and overall survival (43.6% versus 69.0%, p = 0.014) were improved in groups who received surgery and RT/CCRT. Regression analysis controlling for clinicopathologic characteristics, including tumor size, identified radiation as an independent predictor of improved disease-free survival (HR: 0.04, p < 0.001) and overall survival (HR: 0.10, p < 0.001). CONCLUSION: Adjuvant RT/CCRT in patients with pT4N0 OCSCC with mandibular bone involvement is associated with improved disease-free and overall survival. This association was significant regardless of tumor pathologic features such as size or margin status. These findings may help guide physicians in counseling patients regarding risks and benefits of adjuvant RT/CCRT and inform practice guidelines.

Patient-Reported Outcomes of Split-Thickness Skin Grafts for Floor of Mouth Cancer Reconstruction.

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.

Interaction between known risk factors for head and neck cancer and socioeconomic status: the Carolina Head and Neck Cancer Study.

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 < $20,000/year [OR 5.11 (3.61-6.61)] compared to household incomes > $50,000/year [OR 2.47 (1.69-3.25); p interaction < 0.001]. Current drinking was more strongly associated with SCCHN in household incomes < $20,000 [OR 2.91 (2.05-3.78)] compared to > $50,000/year [1.28 (0.97-1.58); p interaction < 0.001]. Current drinkers with less than high school education or income < $20,000 had nearly threefold odds of never-drinkers in the same SES category [OR 2.91 (2.05-3.78); 2.09 (1.39-2.78), respectively]. Our results suggest that the relationship of smoking and alcohol use may be stronger among those of lower SES.

What motivates serodiscordant couples to prevent HIV transmission within their relationships: findings from a PrEP implementation study in Kenya.

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.

184AA3: a xenograft model of ER+ breast adenocarcinoma.

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 CD44(High) subpopulation was discovered, yet their tumor forming ability was far less than CD44(Low) 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.

A secreted bacterial protein protects bacteria from cationic antimicrobial peptides by entrapment in phase-separated droplets.

Mammalian hosts combat bacterial infections through the production of defensive cationic antimicrobial peptides (CAPs). These immune factors are capable of directly killing bacterial invaders; however, many pathogens have evolved resistance evasion mechanisms such as cell surface modification, CAP sequestration, degradation, or efflux. We have discovered that several pathogenic and commensal proteobacteria, including the urgent human threat Neisseria gonorrhoeae, secrete a protein (lactoferrin-binding protein B, LbpB) that contains a low-complexity anionic domain capable of inhibiting the antimicrobial activity of host CAPs. This study focuses on a cattle pathogen, Moraxella bovis, that expresses the largest anionic domain of the LbpB homologs. We used an exhaustive biophysical approach employing circular dichroism, biolayer interferometry, cross-linking mass spectrometry, microscopy, size-exclusion chromatography with multi-angle light scattering coupled to small-angle X-ray scattering (SEC-MALS-SAXS), and NMR to understand the mechanisms of LbpB-mediated protection against CAPs. We found that the anionic domain of this LbpB displays an α-helical secondary structure but lacks a rigid tertiary fold. The addition of antimicrobial peptides derived from lactoferrin (i.e. lactoferricin) to the anionic domain of LbpB or full-length LbpB results in the formation of phase-separated droplets of LbpB together with the antimicrobial peptides. The droplets displayed a low rate of diffusion, suggesting that CAPs become trapped inside and are no longer able to kill bacteria. Our data suggest that pathogens, like M. bovis, leverage anionic intrinsically disordered domains for the broad recognition and neutralization of antimicrobials via the formation of biomolecular condensates.

PARP1 condensates differentially partition DNA repair proteins and enhance DNA ligation.

Poly(ADP-ribose) polymerase 1 (PARP1) is one of the first responders to DNA damage and plays crucial roles in recruiting DNA repair proteins through its activity - poly(ADP-ribosyl)ation (PARylation). The enrichment of DNA repair proteins at sites of DNA damage has been described as the formation of a biomolecular condensate. However, it is not understood how PARP1 and PARylation contribute to the formation and organization of DNA repair condensates. Using recombinant human PARP1 in vitro, we find that PARP1 readily forms viscous biomolecular condensates in a DNA-dependent manner and that this depends on its three zinc finger (ZnF) domains. PARylation enhances PARP1 condensation in a PAR chain-length dependent manner and increases the internal dynamics of PARP1 condensates. DNA and single-strand break repair proteins XRCC1, LigIII, Polß, and FUS partition in PARP1 condensates, although in different patterns. While Polß and FUS are both homogeneously mixed within PARP1 condensates, FUS enrichment is greatly enhanced upon PARylation whereas Polß partitioning is not. XRCC1 and LigIII display an inhomogeneous organization within PARP1 condensates; their enrichment in these multiphase condensates is enhanced by PARylation. Functionally, PARP1 condensates concentrate short DNA fragments and facilitate compaction of long DNA and bridge DNA ends. Furthermore, the presence of PARP1 condensates significantly promotes DNA ligation upon PARylation. These findings provide insight into how PARP1 condensation and PARylation regulate the assembly and biochemical activities in DNA repair foci, which may inform on how PARPs function in other PAR-driven condensates.

Factors Influencing Delay in Diagnosis of Head and Neck Cancer in Rwanda.

OBJECTIVE: Head and neck cancer is a significant contributor to global otolaryngologic disease burden, with a disproportionate impact on low- and middle-income countries. This study investigates the factors contributing to delays in head and neck cancer diagnosis at the University Teaching Hospital of Kigali (CHUK). METHODS: Cross-sectional study of all patients with a pathologic diagnosis of head and neck cancer presenting to CHUK between January 2021 and June 2022. Sociodemographic data, tumor characteristics, and reasons for delay were collected. Univariate and multivariable analyses were undertaken to evaluate risk factors for delays. RESULTS: Eighty-one patients met criteria for inclusion. Median duration from patient first reported symptoms to initial medical consultation was 52 weeks, from initial medical consultation to referral to CHUK was 4 weeks, and from referral to final pathologic diagnosis was 6 weeks. The most common reason for delay to referral to CHUK was financial (37.04%). Patients who visited traditional healers had higher odds of delay between symptom onset and medical consultation (OR 3.51, CI 1.05-11.70). Delays in final diagnosis after referral were most commonly due to OR availability for biopsy (37.04%) and time for pathology results after biopsy (35.80%). OR availability had a significant impact on duration to final diagnosis (OR 59.48, CI 7.17-493.67). Stage 4 disease had the shortest time to final diagnosis (OR 0.05, CI 0.01-0.45). CONCLUSION: Understanding the reasons for delayed diagnosis of head and neck cancer may help guide improvements in care, with the goal of reducing global head and neck burden of disease. LEVEL OF EVIDENCE: 3; prospective non-random follow-up study Laryngoscope, 134:1663-1669, 2024.

The Impact of Venous Anastomosis Technique on Outcomes of Free Tissue Transfer to the Head and Neck.

Objectives: To evaluate the impact of different techniques of microvascular venous anastomosis on the outcome of free tissue transfer to the head and neck. Methods: Retrospective case series of patients undergoing microvascular free tissue transfer (MFTT) from January 2006 to September 2021. Chi-square tests and t-tests were utilized to identify differences in flap outcomes by technique, and log-binomial regression analyses were utilized to identify differences in flap outcomes by technique. Results: A total of 1055 consecutive MFTTs were analyzed. One hundred four cases required a return to the operating room for any reason, and 19 were attributed to venous compromise (18.0%). Ultimately, there were 22 FTT failures requiring complete revision (2.1%). In total, 1055 MFTTs involved 1352 venous anastomoses, ranging from 1 to 3 anastomoses in each case. End-to-end (ETE) was used 1040 times (76.9%) and end-to-side (ETS) 204 times (15.0%). The calculated risk ratio for venous complication for ETS compared with ETE was 1.17 (0.34-3.98). A microvascular coupler was used in 355 cases (33.6%). The calculated risk ratio for coupler compared with suture anastomoses was 0.92 (0.35-2.39). Conclusions: There were no significant difference in regard to outcomes of MFTT when comparing ETE with ETS, nor when comparing coupler with suture anastomoses.

International Collaboration Trends in Facial Plastic and Reconstructive Surgery: A Systematic Bibliometric Scoping Review.

Importance: Research in facial plastic and reconstructive surgery (FPRS) in the global health setting, especially in low- and middle-income countries (LMICs), is increasing year by year. As this work progresses, it will be crucial to include voices and perspectives of individuals living in the LMICs being studied. Objective: To characterize and understand international collaborations in published literature on FPRS care in a global health setting and report patterns in whether these articles included authors from the LMICs in which the studies took place. Evidence Review: A systematic bibliometric scoping review of articles in Scopus from 1971 to 2022 was performed using a set list of search terms; studies were included using predetermined inclusion and exclusion criteria. Studies met criteria for inclusion if the abstract or text contained information regarding surgeons from a different country performing surgery or conducting research in an LMIC within the domain of FPRS. Exclusion criteria were studies that did not mention a facial plastic or reconstructive surgery and studies where both an HIC and LMIC were not mentioned. Findings: A total of 286 studies met criteria for inclusion. The highest percentage of studies (n = 72, 25.2%) were conducted across multiple countries. A total of 120 studies (41.9%) discussed cleft lip/palate. Overall, 141 studies (49.5%) included at least 1 author from the host LMIC; 89 (31.1%) had first authors from LMICs, and 72 (25.2%) had senior authors from LMICs. A total of 79 studies (27.6%) described humanitarian clinical service trips without mentioning research or education in the text. The remaining studies described research, education projects, or a combination. The published literature on humanitarian service trips had the lowest rate of inclusion of a first or senior author from the host LMICs. Conclusions and Relevance: In this systematic bibliometric scoping review, findings showed a general trend of increased international work in the field of FPRS. However, there continues to be a paucity of inclusive authorship trends, with the majority of studies not including first or senior authors from LMICs. The findings presented here encourage new collaborations worldwide, as well as the improvement of existing efforts.

Outcomes of Vascularized Versus Nonvascularized Adipofascial Grafts for Parotidectomy Reconstruction.

Objectives: Parotidectomy defects can leave patients with considerable functional and cosmetic deformities. We aim to compare the success rates and complications associated with vascularized versus nonvascularized adipofascial grafts for reconstruction, including flap failure, return to surgery, infection, and delay to adjuvant treatment. Methods: Retrospective case series of patients undergoing either adipofascial anterolateral thigh (AFALT) free tissue transfer or free fat transfer (FFT) after parotidectomy from January 2010 to January 2020. Group comparisons and logistic regression were used to determine predictors of outcome measures. Results: Seventy-six patients underwent AFALT reconstruction, and 73 patients underwent FFT reconstruction. Patients treated with AFALT reconstruction had more aggressive tumor characteristics and underwent more complex resections, most commonly radical parotidectomy (n = 55, 72.4%). Postoperative complications at both the donor and recipient sites were more common in the FFT group (N = 20, 27.4% in FFT vs. N = 11, 14.5% in AFALT, odds ratio = 0.45, 95% confidence interval = 0.20-1.02, p = 0.052). Conclusions: Although used in more advanced disease and in a more heavily treated wound bed, the AFALT free flap was safe and associated with fewer infectious complications than that offered by FFT.

Mandibular Angle Fractures.

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.

Density of Health Workforce Correlates to Disease Outcomes: Evidence From Global Data in Otolaryngology.

Objective: To better understand the impact of the otolaryngology-specific workforce on the burden of related diseases. Study Design: Retrospective analysis of existing workforce density data as compared with the incidence, mortality, and morbidity data for 4 otolaryngologic diseases. Setting: An overall 138 countries with known otolaryngology-head and neck surgery workforce and epidemiologic data. Methods: We obtained raw data on workforce estimates of ear, nose, and throat surgical specialists from the World Health Organization. Disease burdens for 4 conditions were estimated via 2 ratios, the mortality:incidence ratio (MIR) and YLD:incidence ratio (years lost to disability), as specified in the Global Burden of Disease database. These were correlated to country-specific otolaryngologist density data in univariate and multivariate analyses. Results: Increased density of the ear, nose, and throat workforce correlated with better outcomes for otolaryngologic-treated surgical diseases. A 10% increase in otolaryngology workforce density was associated with a 0.27% reduction in YLD:incidence ratio for chronic otitis media, a 0.94% reduction in MIR for lip and oral cavity cancer, a 1.46% reduction in MIR for laryngeal cancer, and a 1.34% reduction in MIR for pharyngeal cancer (all P < .001)-an effect that remained after adjustment for health systems factors for all conditions but chronic otitis media. Conclusion: The density of the surgical workforce is assumed to affect disease outcomes, but ours is the first analysis to show that increased workforce density for a specific surgical specialty correlates with improved disease outcomes. While there is a consensus to increase access to health care providers, quantifying the effect on disease outcomes is an important metric for those performing health economics modeling, particularly where resources are limited.

Effect of Delay of Care for Patients with Craniomaxillofacial Trauma in Rwanda.

Objectives: Craniomaxillofacial (CMF) trauma represents a significant proportion of global surgical disease burden, disproportionally affecting low- and middle-income countries where care is often delayed. We investigated risk factors for delays to care for patients with CMF trauma presenting to the highest-volume trauma hospital in Rwanda and the impact on complication rates. Study Design: This prospective cohort study comprised all patients with CMF trauma presenting to the University Teaching Hospital of Kigali, Rwanda, between June 1 and October 1, 2020. Setting: Urban referral center in resource-limited setting. Methods: Epidemiologic data were collected, and logistic regression analysis was undertaken to explore risk factors for delays in care and complications. Results: Fifty-four patients (94.4% men) met criteria for inclusion. The mean age was 30 years. A majority of patients presented from a rural setting (n = 34, 63%); the most common cause of trauma was motor vehicle accident (n = 18, 33%); and the most common injury was mandibular fracture (n = 28, 35%). An overall 78% of patients had delayed treatment of the fracture after arrival to the hospital, and 81% of these patients experienced a complication (n = 34, P = .03). Delay in treatment was associated with 4-times greater likelihood of complication (odds ratio, 4.25 [95% CI, 1.08-16.70]; P = .038). Conclusion: Delay in treatment of CMF traumatic injuries correlates with higher rates of complications. Delays most commonly resulted from a lack of surgeon and/or operating room availability or were related to transfers from rural districts. Expansion of the CMF trauma surgical workforce, increased operative capacity, and coordinated transfer care efforts may improve trauma care.

Predicting Adverse Histopathology and Need for Postsurgical Adjuvant Therapy for Human Papilloma Virus-Associated Oropharynx Carcinoma.

OBJECTIVE: 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. STUDY DESIGN: Retrospective review. SETTING: National Cancer Database. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Patterns of Nodal Metastases and Predictors of Occult Disease in HPV-Associated Oropharynx Cancer.

OBJECTIVE: 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. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database (NCDB). METHODS: 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. RESULTS: 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; P = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18; P < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected. CONCLUSION: 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. LEVEL OF EVIDENCE: 4.

Patient-Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma.

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 < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste. CONCLUSIONS: ESOTCCIS patients who undergo R-PC without radiation can expect long-term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R-PC carries the risks of mild speech and/or taste impairments. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:312-318, 2021.

Predictors of Mortality in HPV-Associated Oropharynx Carcinoma Treated With Surgery Alone.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 with >20 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. CONCLUSION: 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. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E423-E435, 2020.