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PurposeIncreased activity of STAT3 is associated with progression of head and neck squamous cell carcinoma (HNSCC). Upstream activators of STAT3, such as JAKs, represent potential targets for therapy of solid tumors, including HNSCC. In this study, we investigated the anticancer effects of ruxolitinib, a clinical JAK1/2 inhibitor, in HNSCC preclinical models, including patient-derived xenografts (PDX) from patients treated on a window-of-opportunity trial.Experimental designHNSCC cell lines were treated with ruxolitinib, and the impact on activated STAT3 levels, cell growth, and colony formation was assessed. PDXs were generated from patients with HNSCC who received a brief course of neoadjuvant ruxolitinib on a clinical trial. The impact of ruxolitinib on tumor growth and STAT3 activation was assessed.ResultsRuxolitinib inhibited STAT3 activation, cellular growth, and colony formation of HNSCC cell lines. Ruxolitinib treatment of mice bearing an HNSCC cell line-derived xenograft significantly inhibited tumor growth compared with vehicle-treated controls. The response of HNSCC PDXs derived from patients on the clinical trial mirrored the responses seen in the neoadjuvant setting. Baseline active STAT3 (pSTAT3) and total STAT3 levels were lower, and ruxolitinib inhibited STAT3 activation in a PDX from a patient whose disease was stable on ruxolitinib, compared with a PDX from a patient whose disease progressed on ruxolitinib and where ruxolitinib treatment had minimal impact on STAT3 activation.ConclusionsRuxolitinib exhibits antitumor effects in HNSCC preclinical models. Baseline pSTAT3 or total STAT3 levels in the tumor may serve as predictive biomarkers to identify patients most likely to respond to ruxolitinib.

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.

BackgroundHPV-positive oropharynx squamous cell cancer (HPV-OPC) patients were initially described as younger, however incidence has increased among older age-groups. It is unknown why some patients present at a younger age and others at a later age.MethodsMulti-institutional prospective study of HPV-OPC cases (n = 163) and matched controls (n = 345) with detailed behavioral survey, and serum tested for HPV antibodies by fluorescent bead-based technology. Age at diagnosis was used to stratify patients into younger (≤50 years), middle-age (51-65), and older (>65).ResultsBy age, demographic characteristics were largely similar, but HPV biomarkers and sexual acts differed. Younger cases were more likely to be HPV16-positive than older cases (100% vs 77%, p = 0.009). Similarly, younger cases were more likely to be HPV16 E6 or E7 seropositive (100% vs 82%, p = 0.03). Younger cases had a higher number of oral sex partners per year, a marker of sexual intensity (sex-years, p = 0.003), but a similar number of lifetime oral sex partners (measure of cumulative sexual exposure), compared to older cases. While sex-years were higher for younger cases and controls, cases had significantly higher sex-years than matched controls in each age-group (p

BackgroundSurvival outcomes for adjuvant chemoradiotherapy (aCRT) and adjuvant radiotherapy (aRT) were compared in patients with oropharyngeal squamous cell carcinoma (OPSCC) with intermediate-risk features.MethodsWe identified 2164 patients with OPSCC in the National Cancer Database without positive margins or extracapsular extension and with at least one intermediate-risk feature: pT3-T4 disease, ≥two positive lymph nodes, level IV/V nodal disease, and/or lymphovascular invasion. We assessed predictors of aCRT use and covariables impacting overall survival.ResultsaCRT was commonly used for both human papillomavirus (HPV)-positive (62.0%) and HPV-negative (64.3%) patients with OPSCC. Higher N stage, level IV/V neck disease, and younger age strongly predicted aCRT utilization. There was no significant survival benefit associated with aCRT vs aRT in HPV-positive (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.62-1.38; P = .71) or HPV-negative (HR, 0.75; 95% CI, 0.51-1.10; P = .15) disease.ConclusionsDespite high rates of utilization, aCRT is not associated with better survival vs aRT for OPSCC with intermediate-risk features, including HPV-negative tumors.

Objective: To define symptomatology and responses to treatment in chronic sialadenitis from sialolithiasis versus duct stenosis and establish a minimal clinically significant difference (MCID) in the validated Obstructive Salivary Problem Impact Test (SPIT). Study Design: Prospective, cohort. Setting: Tertiary‐care center. Methods: Patients completed the SPIT questionnaire at presentation and 3 to 6 months after surgery. SPIT scores and domains were compared between patients with symptomatic sialolithiasis and those with stenosis of a major salivary gland. Results: Seventy‐nine patients completed the SPIT, including 43 (54%) with sialolithiasis and 36 (46%) with stenosis. Stenosis patients displayed greater baseline scores compared to sialolithiasis patients (45.4 ± 19.9 vs 33.3 ± 18.5, P <.013). Frequency and severity of gland swelling and pain (21.9 ± 8.9 vs 17.1 ± 9.6, P =.02) and functional/psychosocial impact subscores were greater in the stenosis versus sialolithiasis groups (18.0 ± 10.9 vs 11.3 ± 9.4, P <.01). For 43 patients who underwent surgical intervention, SPIT scores improved at 3 to 6 months postoperatively in all domains (−18.6 ± 19.4, P <.01). Degree of improvement did not differ between sialolithiasis versus stenosis groups (−22.0 ± 20.9 vs −13.3 ± 15.8, P =.13). The MCID in SPIT score was found to be −13 points. A postoperative SPIT score of less than 10 suggested symptom resolution. Conclusion: When compared to sialolithiasis, chronic salivary obstruction from stenosis is associated with greater baseline SPIT scores, indicating poorer sialadenitis‐related quality of life due to greater symptom frequency and functional impact. Based on SPIT survey outcomes, a score decrease of 13 points or SPIT score <10 represent significant symptom improvement. [ABSTRACT FROM AUTHOR]

Objectives/hypothesisHuman papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV-positive and HPV-negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification STUDY DESIGN: Retrospective case series.MethodsA retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California-San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan-Meier and unadjusted and adjusted Cox regression models.ResultsOne hundred thirty-four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV-positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20-1.07; P = .06) but not HPV-negative (HR: 0.73, 95% CI: 0.43-1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV-positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12-0.96; P = .04). Survival did not vary significantly by race among HPV-positive patients. Among HPV-negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08-0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11-7.36; P = .94) analysis.ConclusionsWomen with HPV-positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV-negative OPSCC. There are no differences in prognosis by race among HPV-positive or HPV-negative patients.Level of evidence4 Laryngoscope, E287-E295, 2018.

Intratumoral stimulatory dendritic cells (SDCs) play an important role in stimulating cytotoxic T cells and driving immune responses against cancer. Understanding the mechanisms that regulate their abundance in the tumor microenvironment (TME) could unveil new therapeutic opportunities. We find that in human melanoma, SDC abundance is associated with intratumoral expression of the gene encoding the cytokine FLT3LG. FLT3LG is predominantly produced by lymphocytes, notably natural killer (NK) cells in mouse and human tumors. NK cells stably form conjugates with SDCs in the mouse TME, and genetic and cellular ablation of NK cells in mice demonstrates their importance in positively regulating SDC abundance in tumor through production of FLT3L. Although anti-PD-1 'checkpoint' immunotherapy for cancer largely targets T cells, we find that NK cell frequency correlates with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with increased overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as an excellent prognostic tool for T cell-directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis as a target for new therapies.

BACKGROUND:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing among older adults. It is unknown whether these trends can be explained by human papillomavirus (HPV) and whether HPV-related tumors remain associated with an improved prognosis among older patients. METHODS:In a retrospective study of OPSCCs diagnosed from 1995 to 2013 at 2 National Comprehensive Cancer Network-designated cancer centers, p16 immunohistochemistry and in situ hybridization (ISH) for HPV-16, high-risk DNA, and/or E6/E7 RNA were performed. The median age at diagnosis was compared by p16 and ISH tumor status. Trends in age were analyzed with nonparametric trends. Survival was analyzed with the Kaplan-Meier method and Cox proportional hazards models. RESULTS:Among 239 patients, 144 (60%) were p16-positive. During 1998-2013, the median age increased among p16-positive patients (Ptrend = .01) but not among p16-negative patients (Ptrend = .71). The median age of p16-positive patients increased from 53 years (interquartile range [IQR] in 1995-2000, 45-65 years) to 58 years (IQR for 2001-2013, 53-64 years). Among patients ≥ 65 years old, the proportion of OPSCCs that were p16-positive increased from 41% during 1995-2000 to 75% during 2007-2013 (Ptrend = .04). Among all age groups, including older patients, a p16-positive tumor status conferred improved overall survival in comparison with a p16-negative status. CONCLUSIONS:The median age at diagnosis for HPV-related OPSCC is increasing as the proportion of OPSCCs caused by HPV rises among older adults. The favorable survival conferred by an HPV-positive tumor status persists in older adults. Cancer 2018;124:2993-9. © 2018 American Cancer Society.

Investigation of human muscle regeneration requires robust methods to purify and transplant muscle stem and progenitor cells that collectively constitute the human satellite cell (HuSC) pool. Existing approaches have yet to make HuSCs widely accessible for researchers, and as a result human muscle stem cell research has advanced slowly. Here, we describe a robust and predictable HuSC purification process that is effective for each human skeletal muscle tested and the development of storage protocols and transplantation models in dystrophin-deficient and wild-type recipients. Enzymatic digestion, magnetic column depletion, and 6-marker flow-cytometric purification enable separation of 104 highly enriched HuSCs per gram of muscle. Cryostorage of HuSCs preserves viability, phenotype, and transplantation potential. Development of enhanced and species-specific transplantation protocols enabled serial HuSC xenotransplantation and recovery. These protocols and models provide an accessible system for basic and translational investigation and clinical development of HuSCs.

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co-morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve-dependent mechanism.

Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34+ cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34+ SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34+ cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34+ derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs.

BackgroundHuman papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs).MethodsThis retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS).ResultsThe study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P = .04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS.ConclusionsFor OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance. Cancer 2017;123:1566-1575. © 2017 American Cancer Society.

ImportanceHuman papillomavirus (HPV) causes an increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs), particularly in white men. The prevalence of HPV among other demographic groups and other anatomic sites of HNSCC is unclear.ObjectiveTo explore the role of HPV tumor status among women and nonwhites with OPSCC and patients with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC).Design, setting, and participantsRetrospective cohort study at 2 tertiary academic centers including cases diagnosed 1995 through 2012, oversampled for minorities and females. A stratified random sample of 863 patients with newly diagnosed SCC of the oral cavity, oropharynx, larynx, or nasopharynx was used.Main outcomes and measuresOutcomes were HPV status as measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH.ResultsOf 863 patients, 551 (63.9%) were male and median age was 58 years (interquartile range, 51-68 years). Among 240 OPSCCs, 144 (60%) were p16 positive (p16+), 115 (48%) were HPV16 DNA ISH positive (ISH16+), and 134 (56%) were positive for any oncogenic HPV type (ISH+). From 1995 to 2012, the proportion of p16+ OPSCC increased significantly among women (from 29% to 77%; P = .005 for trend) and men (36% to 72%; P  .51 for trend). Among OPSCCs, p16 had high sensitivity (100%), specificity (91%), and positive (93%) and negative predictive value (100%) for ISH positivity. In non-OP HNSCCs, p16 had lower sensitivity (83%) and positive predictive value (40%) but high specificity (94%) and negative predictive value (99%) for ISH positivity.Conclusions and relevanceDuring 1995 through 2012, the proportion of OPSCCs caused by HPV has increased significantly. This increase was not restricted to white men but was a consistent trend for women and men, as well as for white and nonwhite racial groups. Few non-OP HNSCCs were HPV related. P16 positivity was a good surrogate for ISH+ tumor status among OPSCC, but not a good surrogate for non-OP HNSCC.

Objective: To prospectively compare the impact of treatment modality on patient‐reported quality of life (QOL) in human papillomavirus‐associated oropharynx squamous cell carcinoma (HPV + OPSCC). Study Design: Prospective cohort study. Setting: Academic medical center. Methods: One hundred one patients with American Joint Committee on Cancer (AJCC) 8th edition T1‐3 N0‐2 HPV + OPSCC completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire and Head and Neck Module pretreatment and 3‐month and 1‐year posttreatment. Mean score changes were compared to published minimal clinically important differences. Results: Patients underwent surgery alone (SA: N = 42, 42%), surgery with adjuvant radiation (S‐RT: N = 10, 10%), surgery with adjuvant chemoradiation (S‐CRT: N = 8, 8%), definitive radiation (RT: N = 11, 11%), or definitive chemoradiation (CRT: N = 30, 30%). SA, S‐[C]RT, and [C]RT patients all reported clinically significant difficulty with sense of taste/smell persisting at 1 year. S‐[C]RT and [C]RT patients reported statistically and clinically significant worse salivary dysfunction and problems with social eating at 1 year than SA. S‐[C]RT patients reported statistically and clinically significant worse fatigue and head and neck pain compared to [C]RT and SA patients at 3 months, but normalized at 1 year. S‐CRT compared to S‐RT had statistically and clinically worse physical and role functioning and swallowing difficulties at 3 months but this difference was resolved by 1‐year posttreatment. Conclusion: HPV + OPSCC patients after SA report the lowest posttreatment QOL impact, whereas after S‐CRT report the highest symptom burden. Careful selection for definitive surgery is important given the possibility of adjuvant CRT. Patients can experience persistent sense taste and smell difficulties at 1 year with all treatment modalities. Level of Evidence: 3 Laryngoscope, 134:1687–1695, 2024 [ABSTRACT FROM AUTHOR]

BackgroundHead and neck cancer is often managed with a combination of surgery, radiation therapy, and chemotherapy, and skin toxicity is not uncommon. Xanthogranuloma is a pathological finding resulting from an inflammatory reaction that has not been previously reported following head and neck radiation therapy.Case presentationA patient with squamous cell carcinoma of the oropharynx, treated with definitive chemoradiation and hyperthermia, presented at eight-month follow-up with an in-field cutaneous lesion in the low neck, initially concerning for recurrent tumor. Biopsy showed xanthogranuloma and the patient underwent complete resection with congruent surgical pathology. The patient remained free of malignancy but continued to experience wound healing difficulties at the resection site which resolved with specialized wound care and hyperbaric oxygen.ConclusionsSkin toxicity is not uncommon in patients with head and neck cancer treated with radiation therapy. Awareness of unusual pathologic sequelae, such as xanthogranuloma, is needed to provide patient counseling while continuing appropriate surveillance for recurrent malignancy.

Background: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. Methods: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6‐month progression‐free survival (PFS) and secondary outcome of 2‐year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. Results: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6‐month PFS (HR 1.30, 95% CI 1.10–1.54, p = 0.002) and 2‐year OS (HR 1.33, 95% CI 1.07–1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17–76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67–75.77, p = 0.013). Conclusions: Higher pretreatment NLR was independently associated with inferior 6‐month PFS and 2‐year OS in pembrolizumab‐treated R/M SGC patients. [ABSTRACT FROM AUTHOR]

Background/Objective: Quantitative swallowing displacement kinematics evolve in patients treated for oropharyngeal squamous cell carcinoma (OPSCC). We aimed to longitudinally assess these measurements and correlate them with functional swallowing outcomes. Method: A retrospective review was conducted on patients with OPSCC treated with definitive (chemo)radiation ([C]RT) or surgery with adjuvant (chemo)radiation (S‐[C]RT) who completed at least two videofluoroscopic swallow studies (VFSS). Longitudinal analysis was accomplished via mixed‐effects logistic regression for the Functional Oral Intake Scale (FOIS), and Penetration Aspiration Scale (PAS), and mixed‐effects linear regression for kinematic measures. Spearman's correlation was conducted between changes in FOIS/PAS and kinematic measures. Results: Ninety‐seven patients (76 males; mean age 61) completed 245 VFSS studies. A total of 94% had human papillomavirus (HPV)/p16 positive OPSCC and 74% were T0–T2. Sixty‐four patients underwent [C]RT while 33 patients underwent S‐[C]RT. After treatment, posterior pharyngeal wall at hold (PPWhold) increased 3.2 standard deviation (SD) between 0 and 6 months (p < 0.001), then decreased 2.2 SD between 6 and 12 months (p < 0.001) and did not return to baseline. Hyoid‐to‐larynx (HL) (p = 0.046) and maximal hyoid displacement (Hmax) + HL (p = 0.042) increased between 6 and 12 months. Hmax (p = 0.020) and Hmax + HL (p < 0.001) decreased between 12–24 months beyond baseline values. The decrease in HL and increase in PPWhold (p < 0.05) correlated with an increase in PAS. From baseline, increased pharyngeal constriction ratio correlated with decreased FOIS and PPWhold (p < 0.05). Conclusions: Quantitative swallowing kinematic measures can effectively track changes in swallowing physiology. Increased PPWhold and restricted hyolaryngeal movement were seen in patients with OPSCC after treatment and correlated with a change in swallowing outcome, emphasizing the need for serial VFSS monitoring and targeted intervention. Level of Evidence: 3 Laryngoscope, 133:1339–1348, 2023 [ABSTRACT FROM AUTHOR]

Objective: The objective is to evaluate the long‐term impact of sialendoscopic‐assisted salivary duct surgery (SASDS) on sialadenitis symptoms using the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire. Methods: The COSS questionnaire, which scores symptoms on a 0–100 scale, was administered prospectively to adult patients pre‐operatively, 1‐year, and 6‐years post‐operatively. We examined COSS scores and categories representing complete (<10), partial (10–25), and no (>25) resolution of symptoms with attention to factors significantly associated with incomplete resolution (≥10). Results: Approximately 6‐years after SASDS, 111 patients reported scores for 128 symptomatic glands (72 with sialolithiasis, 56 without sialolithiasis). For glands with sialolithiasis, the median COSS score pre‐SASDS was 27.5 (interquartile range [IQR]: 13.5–43), which was significantly reduced to 1.0 (IQR: 0–5.5) at 1‐year and 1.5 (IQR 0–5) at 6‐years postoperatively. Glands without sialolithiasis had a median COSS score of 40.5 (IQR: 23–52.5) preoperatively, that significantly reduced to 13.5 (IQR 5–21) at 1‐year and 14 (IQR 6.5–25.5) at 6‐years post‐operatively. There was no significant difference in scores from 1‐ to 6‐years. Intraoperative presence of sialolith, absence of stenosis, stenosis in the distal duct, and submandibular gland involvement were significant predictors of complete resolution of symptoms at 6‐years. Conclusion: Approximately 6‐years after SASDS for sialadenitis, the majority of patients have durable symptom improvement. The sialolithiasis group had higher rates of complete resolution compared to the non‐sialolithiasis group. Presence of ductal stenosis on sialendoscopy, non‐distal stenoses, and parotid gland involvement were risk factors for persistent long‐term sialadenitis symptoms. Laryngoscope, 133:792–800, 2023 [ABSTRACT FROM AUTHOR]

Objective: The Chronic Obstructive Sialadenitis Symptoms questionnaire (COSS) was created to assess chronic sialadenitis symptoms and treatment response, but its development lacked patient input and validation. We analyzed COSS responses and feedback from sialadenitis patients and physician experts to create the novel obstructive Salivary Problem Impact Test (SPIT), a new standardized measure of sialadenitis‐associated symptoms. Methods: We analyzed COSS responses via exploratory factor analysis (EFA) to identify essential symptom domains and reduce overlap in questions. Sialadenitis patients evaluated the significance of index symptoms identified from the literature review. Expert physicians rated symptom relevance in clinical assessment. An updated questionnaire (SPIT) was piloted with both patient and expert interviews to optimize structure and readability. The SPIT was assessed for internal consistency, construct validity, and test–retest stability. Results: EFA of 310 COSS responses demonstrated 3 main symptom domains (functional impact, pain, swelling) that explained 58.4% of response variance. Results were not statistically different when collapsing from 11 to 5 question response options. Experts (n = 5) ranked gland swelling, mealtime pain, and foul taste as most clinically important, while patients (n = 12) ranked swelling, non‐mealtime pain, and difficulty eating as most bothersome. Most patients experienced sialadenitis‐related functional or psychosocial impairment. Following interviews for question refinement, a 25‐question survey was finalized. SPIT responses from 50 sialadenitis patients demonstrated internal consistency (Cronbach's alpha = 0.96), 14‐day stability (p < 0.001), and agreement with Oral Health Impact Profile‐14 scores (p < 0.0001). Conclusions: We developed the SPIT instrument to improve usability and content validity in chronic sialadenitis evaluation. The psychometric assessment demonstrated high construct validity and test–retest reliability. Further work will assess longitudinal changes with treatment. Level of Evidence: 4 Laryngoscope, 133:539–546, 2023 [ABSTRACT FROM AUTHOR]