Search

Objective(s): A subset of laryngeal squamous cell carcinoma (LSCC) patients undergoing larynx preserving treatment ultimately require total laryngectomy (TL) for oncologic or functional reasons. This study aims to identify TL risk factors in these patients. Methods: Retrospective cohort study using Veterans Affairs (VA) database. T1–T4 LSCC cases treated with primary radiotherapy (XRT) or chemoradiotherapy (CRT) were assessed for TL and recurrence. Binary logistic and Cox regression and Kaplan–Meier analyses were implemented. Results: Of 5390 cases, 863 (16.0%) underwent TL. On multivariable analysis, age (adjusted odds ratio: 0.97 [0.96–0.98]; p <.001) and N3 disease (0.42 [0.18–1.00]; p =.050) were associated with reduced risk of TL, whereas current alcohol use (1.22 [1.04–1.43]; p =.015) and >T1 disease (T2, 1.76 [1.44–2.17]; p <.001; T3, 2.06 [1.58–2.68]; p <.001; T4, 1.79 [1.26–2.53]; p =.001) were associated with increased risk of TL. However, N2 (adjusted hazard ratio: 1.30 [1.10–1.55]; p =.003) and N3 (2.02 [1.25–3.26]; p =.004) disease were associated with an increased risk for local recurrence. Compared to XRT, treatment with CRT was associated with reduced risk for local recurrence after adjusting for other factors (0.84 [0.70–0.99]; p =.044). Those who do not receive TL following local recurrence have poorer disease‐specific survival (log‐rank, p <.001). In patients without local recurrence, N2 disease was associated with a fourfold increase in risk of TL (4.24 [1.83–9.82]; p <.001). Conclusion: Advanced nodal stage was associated with reduced rates of salvage TL in the setting of local recurrence, and subsequent worse prognosis after recurrence. Conversely, advanced nodal stage may increase the risk for functional salvage TL in patients without recurrence. Level of Evidence: Level 3. [ABSTRACT FROM AUTHOR]

Background: Understanding biological differences between different racial groups of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies.Methods: This study evaluated whether there were morphologic differences between HPV-associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis-derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin-eosin images and previously has been prognostic in HPV-associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease-free survival in their previous study, TTR , is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW for Whites, for risk stratification.Results: MuNI was statistically significantly different between Black (mean, 3.88e-4; median, 3.67e-04) and White patients (mean, 3.36e-04; median, 2.99e-04), with p = .0078. Using TTR , MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 (p = .002; 95% confidence interval [CI], 1.21-2.43) and in White patients with HR of 1.72 (p = .005; 95% CI, 1.18-2.51). Population-specific cutoff, TW , yielded improved HR of 1.77 (p = .003; 95% CI, 1.21-2.58) for White patients, whereas TB did not improve risk-stratification in Black patients with HR of 0.6 (p = .3; HR, 0.6; 95% CI, 0.2-1.80).Conclusions: Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population-specific prognostic biomarkers for personalized risk stratification strategies for HPV-associated OPSCC patients. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To evaluate trends in contemporary positive surgical margin incidence in cT1‐T2 oral cavity squamous cell carcinoma and to evaluate factors associated with surgical margin status. Study Design: Retrospective analysis of large dataset. Methods: Retrospective analysis of the National Cancer Database. Results: Between 2004 and 2016, 39,818 patients with cT1 or cT2 oral cavity squamous cell carcinoma received primary curative‐intent surgery. Positive surgical margins were present in 7.95% of patients, and univariable adjusted probability of positive surgical margins over the study period declined by 1% per year (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98–1.0; P =.049). Multivariable regression revealed the annual rate of positive surgical margins declined significantly (OR, 0.95 per year; 95% CI, 0.92–0.97; P <.001). Factors associated with increased odds of positive surgical margins included cT2 disease, subsite, understaged disease, lymphovascular invasion, tumor grade, and positive lymph nodes. Race and socioeconomic status were not associated with surgical margin status. Treatment at an academic center was associated with increased time to definitive surgery (median 35 days IQR 22–50 vs. median 27 days IQR 14–42; P <.001) and a 20% reduction in positive surgical margin rate (OR, 0.80; 95% CI, 0.71–0.90; P <.001). Treatment at high‐volume centers was less likely to be associated with positive surgical margins (OR, 0.85; 95% CI, 0.74–0.98; P =.02). Conclusion: Surgical subsite, clinical T and N category, presence of lymphovascular invasion, and histologic grade were independent predictors of positive surgical margins. Patients are increasingly being treated at high‐volume and academic centers. Overall, the rate of positive surgical margins in cT1‐T2 oral cavity squamous cell carcinoma is decreasing. Level of Evidence: 4 Laryngoscope, 132:1962–1970, 2022 [ABSTRACT FROM AUTHOR]

Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises the possibility that standard of care treatments delivered in concert may compromise the tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models in which we map tumor-draining lymphatics and develop models for regional lymphablation with surgery or radiation. We find that lymphablation eliminates the tumor ICI response, worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, within tumor-draining lymphatics, we observe an upregulation of conventional type I dendritic cells and type I interferon signaling and show that both are necessary for the ICI response and lost with lymphablation. Ultimately, we provide a mechanistic understanding of how standard oncologic therapies targeting regional lymphatics impact the tumor response to immune-oncology therapy in order to define rational, lymphatic-preserving treatment sequences that mobilize systemic antitumor immunity, achieve optimal tumor responses, control regional metastatic disease, and confer durable antitumor immunity. Response rates to immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) remain low. Here the authors show that ablative treatment of tumor-draining regional lymphatics, a standard of care approach in patients, impairs the tumor response to ICI in preclinical HNSCC models. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) represents a highly prevalent and deadly malignancy worldwide. The prognosis for locoregionally advanced HNSCC has not appreciably improved over the past 30 years despite advances in surgical, radiation, and targeted therapies and less than 20% of HNSCC patients respond to recently approved immune checkpoint inhibitors. The Hippo signaling pathway, originally discovered as a mechanism regulating tissue growth and organ size, transduces intracellular and extracellular signals to regulate the transcriptional co-activators YAP and TAZ. Alterations in the Hippo pathway resulting in persistent YAP and TAZ activation have emerged as major oncogenic drivers. Our analysis of the human HNSCC oncogenome revealed multiple genomic alterations impairing Hippo signaling and activating YAP and TAZ, which in turn contribute to HNSCC development. This includes mutations and deletions of the FAT1 gene (29%) and amplification of the WWTR1 (encoding TAZ, 14%) and YAP1 genes (8%), together representing one of the most genetically altered signaling mechanisms in this malignancy. Here, we discuss key elements of the mammalian Hippo pathway, detail mechanisms by which perturbations in Hippo signaling promote HNSCC initiation and progression and outline emerging strategies to target Hippo signaling vulnerabilities as part of novel multimodal precision therapies for HNSCC. [ABSTRACT FROM AUTHOR]

Background: The objective is to study the effect of Medicaid expansion on postoperative radiation therapy (PORT) delay in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Patients from the National Cancer Database with HNSCC undergoing curative‐intent surgery in the 2 years before and after Medicaid expansion were analyzed (n = 11 717) using the difference‐in‐differences technique to study the effect on PORT delay. Results: The rate of PORT delay before and after expansion was 66.0% and 66.9%, respectively. Medicaid patients had more frequent PORT delay than privately insured patients (pre‐expansion 77.2% vs. 59.4%, p < 0.001; post‐expansion 76.5% vs. 60.9%, p < 0.001). Medicaid expansion had no effect on PORT delay [hazard ratio 0.95, 95% confidence interval 0.81–1.12]. Supplemental analyses revealed that pathologic stage, number of treating facilities, and comorbidities were among several factors associated with PORT delay in the cohort. Conclusion: PORT delay is unacceptably frequent. Improvement in timely adjuvant therapy requires more than Medicaid expansion. [ABSTRACT FROM AUTHOR]

Background: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus–associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. Methods: The authors performed a 12‐institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0‐3 N3 M0) treated with surgery alone with 6 months or more of follow‐up using univariate and multivariate analyses. Results: The 2‐year outcomes for the entire cohort were 91% (182 of 200) disease‐free survival (DFS), 100% (200 of 200) disease‐specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow‐up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2‐year overall salvage radiation need of 4.5% (9 of 200). The 2‐year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0‐2 N2a‐N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). Conclusions: With careful selection, surgery alone for AJCC 7th pT0‐T2N0‐N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short‐term follow‐up, these data support further investigation of treatment de‐escalation in this population. With careful selection, surgery alone for human papillomavirus–associated oropharynx squamous cell carcinoma, American Joint Committee on Cancer 7th edition pT0‐2, N2a‐N2b with 1 to 3 pathologic lymph nodes without perineural invasion, extranodal extension, or positive margins can result in favorable disease‐free survival, disease‐specific survival, overall survival, and salvage treatment success rates. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Subglottic squamous cell carcinoma (SSCC) is a rare cancer with limited evidence‐based treatment guidelines. This study aimed to describe the treatment patterns for SSCC and to determine which treatments provide the best overall survival. Study Design: Retrospective database review. Methods: The National Cancer Database (NCDB) was queried for patients treated for SSCC from 2004 through 2014. Overall survival (OS) rates were determined by the Kaplan‐Meier method. Clinicopathologic characteristics were assessed by univariable and multivariable Cox proportional hazards models, which corrected for age, sex, race, insurance status, income quartile, residence, Charlson‐Deyo comorbidity score, facility type providing treatment, tumor grade, and clinical N and T category. Results: In this cohort of 549 patients with SSCC, the 5‐year OS was 48.2%. SSCC presented at an advanced stage (American Joint Committee on Cancer stage III or IV) in 60.1% of cases; 78.3% of cases had no nodal metastases. Among only stage IV cases, multivariable analysis showed that radiotherapy (RT) (hazard ratio [HR] = 5.944; 95% confidence interval [CI]: 2.76‐12.8; P <.001) and chemoradiotherapy (CRT) (HR = 2.321; 95% CI: 1.36‐3.97; P =.002) were both associated with decreased 5‐year OS compared to a group consisting of all surgeries. When this analysis was repeated for only stage III cases, RT (HR = 1.134; 95% CI: 0.38‐3.37; P =.821) and CRT (HR = 1.784; 95% CI: 0.78‐4.08; P =.170) were equivalent to surgery. Conclusions: Using the NCDB to study the largest cohort of SSCC with known staging and treatment, primary surgery may provide a better 5‐year OS in advanced‐stage SSCC. Level of Evidence: 4 Laryngoscope, 131:E1117–E1124, 2021 [ABSTRACT FROM AUTHOR]

Background: Recurrent head and neck squamous cell carcinoma (HNSCC) after radiation is associated with poor survival, and management of the clinically negative (N0) neck during salvage surgery is controversial. Methods: Studies were selected according to preferred reporting items for systematic reviews and meta‐analyses guidelines. Inclusion criteria were patients with HNSCC, prior radiation to the lateral neck nodal basin, undergoing salvage surgery for local recurrence, persistence or second primary, and N0 at time of salvage. Eleven studies with a total of 382 patients met inclusion criteria. Results: The rate of occult metastasis was 15.4%. The pooled rate of occult nodal metastasis was 16.2% for oral cavity, 12.9% for oropharynx, 23.7% for hypopharynx, and 27.3% for supraglottic or transglottic tumors. There was a significantly higher relative risk of occult metastasis for locally advanced tumors. Conclusion: Elective neck dissection at time of salvage surgery should be considered based on subsite, T classification, and prior history of nodal metastasis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance characteristics of seven predetermined imaging features on pretreatment computed tomography (CT) in identifying extranodal extension (ENE) in cervical lymph node metastases from human papillomavirus-positive oropharyngeal carcinoma (HPV-OPC).Study Design: Retrospective study.Methods: Seventy-three patients with HPV-OPC who underwent primary surgery and cervical lymph node dissection were included. Preoperative contrast-enhanced CT (cCT) imaging was evaluated by two radiologists blinded to pathological results. Each cCT was scored for seven imaging features of interest: 1) indistinct capsular contours, 2) irregular nodal margins, 3) perinodal fat stranding, 4) perinodal fat planes, 5) nodal necrosis, 6) intranodal cysts, and 7) nodal matting. Logistic regression was employed to determine radiologist-specific odds ratios (OR) of predicting ENE for each imaging feature and radiologist-specific receiver operating characteristics (sensitivity [Sn], specificity [Sp], area under the curve [AUC], positive predictive value [PPV], negative predictive value [NPV]) for each imaging feature.Results: Thirty-two (44%) patients had ENE-positive lymph nodes. The presence of irregular margins (ORA = 12.3, 95% confidence interval [CI]A = 2.3-65.9; ORB = 7.0, 95% CIB = 1.4-36.3) and absence of perinodal fat plane (ORA = 6.8, 95% CIA = 2.0-23.3; ORB = 14.2, 95% CIB = 1.7-120.5) were significantly associated with ENE for each radiologist. Irregular nodal margin status was most specific for ENE (SnA = 45%, SpA = 94%, AUCA = 69%, PPVA = 82%, NPVA = 73%; SnB = 28%, SpB = 95%, AUCB = 61%, PPVB = 80%, NPVB = 64%). Absence of perinodal fat plane was most sensitive for ENE (SnA = 87%, SpA = 50%, AUCA = 69%, PPVA = 59%, NPVA = 62%; SnB = 96%, SpB = 34%, AUCB = 65%, PPVB = 53%, NPVB = 63%).Conclusions: Of the seven imaging features hypothesized to be associated with ENE-status, the presence of irregular nodal margins and absence of perinodal fat plane were the most specific and sensitive features, respectively.Level Of Evidence: 4 Laryngoscope, 130:1479-1486, 2020. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To evaluate if a simple method for assessing tumor-infiltrating lymphocytes (TIL) in primary tumor specimens improves the prognostic value of the American Joint Committee on Cancer, 8th Edition (AJCC8) cancer staging system in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-OPC).Study Design: Retrospective study.Methods: In this study, TIL density was quantified on hematoxylin and eosin (H&E)-stained specimens from patients presenting to Johns Hopkins Hospital between 2009 and 2017 who underwent primary surgical therapy and had primary tumor specimens available for analysis. The prognostic effect of TIL density was evaluated by Kaplan-Meier method and Cox proportional hazards models considering recurrence-free survival (RFS) as the primary outcome.Results: This study included 132 patients. Ninety-five percent were classified by clinical criteria with AJCC8 early-stage disease (stage I: 82%, stage II: 13%). After 84 months of follow-up, 15 recurrences were observed. Among clinically early-stage disease, TILhigh status was associated with improved RFS compared to TILlow (P = .002). Adjusted analysis showed TILhigh status was associated with 79% lower risk of recurrence than TILlow (adjusted hazard ratio [aHR]: 0.210, 95% confidence interval [CI]: 0.061-0.723). In clinical stage I disease, TILhigh status was associated with improved RFS compared to TILlow in both univariate and multivariate analyses (hazard ratio: 0.235, P = .021; aHR: 0.218; 95% CI: 0.058-0.822). TIL density similarly stratified risk in pathologically staged disease.Conclusions: In patients with AJCC8 stage I disease, low TIL density was associated with diminished RFS. Our data suggest that assessing TIL density on H&E-stained primary tumor specimens may enhance the prognostic resolution of the AJCC8 staging criteria for HPV-OPC.Level Of Evidence: 4 Laryngoscope, 130:930-938, 2020. [ABSTRACT FROM AUTHOR]

Objectives: The impact of positive tumor margin status and other clinicopathological factors on prognosis in early stage glottic squamous cell carcinoma (SCC) treated with transoral laser microsurgery (TLM) remains unclear. This study examined overall survival (OS) rates of patients with positive tumor margin status compared to negative tumor margin status after TLM in clinical T1-2 glottic SCC.Materials and Methods: The National Cancer Data Base (NCDB) was queried for patients who underwent resection of T1-2 glottic SCC by TLM. Patients were treated from 2004 to 2013. Overall survival was assessed with Kaplan-Meier curve analysis, and univariate and multivariate Cox proportional hazards analysis. Differences in clinicopathologic factors between positive and negative margin groups were compared using Pearson Chi-squared analysis.Results: Of 747 patients meeting inclusion criteria, 598 (80.1%) had negative margins. Median follow-up time was 48.0 months. Unadjusted 5-year OS for positive margins (80.0%) was lower compared to that of negative tumor margins (82.9%), but this was not statistically significant (P = 0.265). This persisted after multivariate analysis (P = 0.960). When tumors were stratified by T stage (647 T1, 100 T2), unadjusted 5-year OS based on margin status remained statistically insignificant for both T1 (P = 0.933) and T2 tumors (P = 0.350).Conclusion: Positive margins did not negatively impact overall survival among patients with TLM-treated early-stage glottic cancer. This finding might be useful clinically in deciding treatment modality for early stage glottic SCC. [ABSTRACT FROM AUTHOR]

Objective: Basaloid squamous cell histology is a rare variant that accounts for about 2% of all head and neck squamous cell laryngeal carcinomas. The purpose of this study was to examine overall survival rates of patients according to treatment, stage, and laryngeal subsite.Study Design: Retrospective analysis.Setting: National Cancer Database (NCDB).Subjects and Methods: The NCDB was queried for patients with basaloid squamous cell carcinoma (BSCC) who were treated from 2004 to 2014. Five-year overall survival rates were determined by the Kaplan-Meier method. Univariate and multivariate analysis was used to identify factors correlated with 5-year overall survival.Results: The NCDB identified 440 patients meeting inclusion criteria. Median follow-up time was 31.2 months. On univariate analysis, the treatment modalities assessed (surgery alone, surgery with radiotherapy, surgery with chemoradiotherapy, radiotherapy, chemoradiotherapy) did not differ in their survival benefit. On multivariate analysis, only chemoradiotherapy (hazard ratio, 0.587; 95% CI, 0.37-0.93; P = .022) was associated with improved survival. All treatment modalities performed similarly between stage I and II tumors ( P = .340) and stage III and IV tumors ( P = .154).Conclusion: This study represents the largest laryngeal BSCC series to date. We found that chemoradiotherapy was associated with improved 5-year overall survival of laryngeal BSCC on multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: In the era of deintensification, little data are available regarding patients' treatment preferences. The current study evaluated treatment‐related priorities, concerns, and regret among patients with head and neck squamous cell cancer (HNSCC). Methods: A total of 150 patients with HNSCC ranked the importance of 10 nononcologic treatment goals relative to the oncologic goals of cure and survival. The level of concern regarding 11 issues and decision regret was recorded. Median rank was reported overall, and factors associated with odds of rank as a top 3 priority were modeled using logistic regression. Results: Among the treatment effects analyzed, the odds of being a top 3 priority was especially high for cure (odds, 9.17; 95% confidence interval [95% CI], 5.05‐16.63), followed by survival and swallow (odds, 1.26 [95% CI, 0.88‐1.80] and odds, 0.85 [95% CI, 0.59‐1.21], respectively). Prioritization of cure, survival, and swallow was similar based on human papillomavirus (HPV) tumor status. By increasing decade of age, older participants were found to be significantly less likely than younger individuals to prioritize survival (odds ratio, 0.72; 95% CI, 0.52‐1.00). Concerns regarding mortality (P = .04) and transmission of HPV to the patient's spouse (P = .03) were more frequent among participants with HPV‐associated HNSCC. Regret increased with additional treatment modalities (P = .02). Conclusions: Patients with HNSCC overwhelming prioritize cure, followed by survival and swallow. The decreased prioritization of survival by older age supports further examination of treatment preference by age. The precedence of oncologic over nononcologic priorities among patients regardless of HPV tumor status supports the conservative adoption of deintensification regimens until the interplay between competing oncologic and nononcologic treatment goals is better understood. When asked to rank treatment‐related priorities, patients with head and neck squamous cell cancer overwhelmingly prioritize cure, followed by survival and swallow. The results appear to be similar by human papillomavirus tumor status, supporting the conservative adoption of deintensification regimens until the interplay between competing oncologic and nononcologic treatment goals is better understood. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the influence of sex and race/ethnicity upon prevalence trends of human papillomavirus (HPV) in oropharyngeal cancer (OPC) and survival after OPC.Method: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with OPC between 2010 and 2015. Outcomes were HPV status of tumor specimens and overall survival. Sex- and race-stratified trends in HPV prevalence were estimated using generalized linear modeling. The influence of sex, race, and HPV tumor status on overall survival was compared by Kaplan-Meier method and Cox Proportional Hazards models.Results: This analysis included 20,886 HPV-positive and 10,364 HPV-negative OPC patients. The prevalence of HPV-positive tumors was higher among men (70.6%) than women (56.3%) and increased significantly over time at a rate of 3.5% and 3.2% per year among men and women, respectively. The prevalence of HPV-positive tumors was highest among whites (70.2%), followed by Hispanics (61.3%), Asians (55.8%), and blacks (46.3%). Blacks and Hispanics experienced significantly more rapid increases in prevalence of HPV-positive tumors over time compared with whites (6.5% vs 5.6% vs 3.2% per year, respectively). In HPV-positive OPC, neither sex nor race/ethnicity was associated with survival among patients with HPV-positive OPC. In contrast, for HPV-negative OPC, risk of death was significantly higher for women versus men (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.08-1.26) and blacks versus whites (aHR, 1.21; 95% CI, 1.10-1.33).Conclusion: The prevalence of HPV-positive tumors is increasing for all sex and race/ethnicity groups in the United States. Sex and race are independently associated with survival for HPV-negative but not HPV-positive OPC. [ABSTRACT FROM AUTHOR]

Objective: To compare transcervical ultrasonography (US) to standard cross-sectional imaging for the visualization of human papillomavirus-related oropharyngeal cancer (HPV-OPC).Materials and Methods: Patients with HPV-OPC and available standard imaging (CT and/or MRI) were identified in clinic and prospectively enrolled. US was performed to visualize the oropharynx and lymph nodes. Tumor characteristics across imaging modalities were evaluated (CT versus MRI, and US versus standard imaging (SI)).Results: Forty-three patients were included. The overall blinded detection rates for CT and MRI were 83% and 71%, respectively. The unblinded detection rate for US was 98%. Agreement of tumor anatomic subsite was moderate for both CT vs MRI (κ = 0.59) and US vs SI (κ = 0.47). Comparison of tumor size by CT and MRI showed statistically significant correlations in craniocaudal (CC), anteroposterior (AP), and mediolateral (ML) dimensions (RhoCC = 0.51, pCC = 0.038; RhoAP = 0.81, pAP < 0.0001; RhoML = 0.57, pML = 0.012). Tumor size estimates by US and SI showed statistically significant correlations in CC and AP, but not ML (RhoCC = 0.60, pCC = 0.003; RhoAP = 0.71, pAP < 0.0001; RhoML = 0.30, pML = 0.08). Tumor volume estimates improved correlations between US and SI (Rho = 0.66, p < 0.0001). Stratification of US patients into early and late imaging studies demonstrated an increase in correlation strength from early (Rho = 0.32, p = 0.32) to late groups (Rho = 0.77, p < 0.0001) demonstrating that ultrasound accuracy improved with experience.Conclusions: Our findings suggest that transcervical ultrasonography is a sensitive and relatively accurate adjunct to standard imaging for the evaluation of oropharyngeal tumors. Its cost, portability, and potential for in-clinic and serial imaging render US an attractive modality to further develop for imaging oropharyngeal tumors. [ABSTRACT FROM AUTHOR]

Objective: To examine reader performance in evaluating oropharyngeal anatomy on ultrasonography.Materials and Methods: Ultrasound images of the oropharynx comprising normal and malignant anatomic variants were organized into slideshows. Slideshows were administered to 6 readers blinded to participant tumor status and with varying experience reading oropharyngeal sonograms. A training slideshow oriented readers to images of the oropharynx with and without malignant lesions. Readers then evaluated images in a test slideshow for tumor presence and marked orthogonal long and short dimensions of the tumor. Results were analyzed for accuracy, sensitivity, specificity, inter-reader agreement, and measurement error relative to prospectively-identified reference measurements.Results: Eighty-seven percent of base of tongue (BOT) sonograms were identified correctly by a majority of readers. In identifying BOT tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 79%, 73%, 85%, and 0.51, respectively. Median measurement error in the long and short axes for BOT tumors was -2.6% (range: -40% to 29%) and -2.6% (range: -56% to 156%), respectively. Eighty-four percent of palatine tonsil sonograms were identified correctly by a majority of readers. In identifying tonsil tumors, median accuracy, sensitivity, specificity, and Fleiss's kappa were 77%, 74%, 78%, and 0.41, respectively. Median measurement error in the long and short axes for tonsil tumors was 3.8% (range: -45% to 32%) and -6.5% (range: -83% to 42%), respectively.Conclusions: Overall, US has clinically useful sensitivity for identification of oropharyngeal carcinoma among readers of diverse clinical backgrounds and experience. US may be useful for the evaluation of features such as tumor dimensions. [ABSTRACT FROM AUTHOR]

This review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV-positive HNSCC and the genome-wide changes associated with this disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To review recent literature on human papillomavirus-related (HPV-positive) oropharyngeal squamous cell carcinoma (OPC) and focus on implications of recurrent and metastatic disease. Methods Primary articles from 1990 to 2016 indexed in MEDLINE (1) pertaining to the epidemiology of HPV-positive OPC and (2) providing clinical insight into recurrent and metastatic OPC. Results The incidence of HPV-positive OPC is increasing globally. HPV-positive OPC is a subtype with distinct molecular and clinical features including enhanced treatment response and improved overall survival. While disease recurrence is less common in patients with HPV-positive OPC, up to 36% of patients experience treatment failure within eight years. Recurrent and metastatic OPC has historically signified poor prognosis, however recent data are challenging this dogma. Here, we discuss recurrent and metastatic OPC in the context of HPV tumor status. Conclusion HPV-positive OPC exhibits distinct genetic, cellular, epidemiological, and clinical features from HPV-negative OPC. HPV tumor status is emerging as a marker indicative of improved prognosis after disease progression in both locoregionally recurrent and distant metastatic OPC. Level of Evidence N/A. [ABSTRACT FROM AUTHOR]

• There is a survival benefit to primary tumor detection regardless of HPV status. • Oropharyngeal primary tumor detection rates are increasing over time. • Female, non-white, and HPV negative patients have lower odds of primary detection. Head and neck cancer of unknown primary (CUP) poses significant therapeutic challenges. We compare CUP and oropharyngeal primary (OP) cases to identify factors associated with tumor detection. The 2004–2019 National Cancer Database was queried to identify CUP and OP cases based on clinical and pathologic TNM staging. Clinical and demographic characteristics were compared by primary detection and HPV status with descriptive statistics. Multivariable logistic regression models to characterize OP detection were constructed. Among HPV-positive and negative patients, respectively, OP and CUP patients were matched by clinical nodal disease. Cox proportional-hazards models were constructed using matched cohorts to characterize survival. 81,053 CUP and OP cases were identified; 64.3 % were HPV-positive. OP detection increased over time in HPV-positive and negative disease. HPV-positive status had higher odds of OP detection (odds ratio (OR) = 1.77, p < 0.001), while females (OR = 0.95, p = 0.008), and black (OR = 0.82, p < 0.001) and Asian (OR = 0.7, p < 0.001) patients had lower odds compared to males and whites, respectively. In HPV-positive and negative disease, OP patients had higher 2 and 5-year survival rates than CUP (p < 0.001). Primary detection status conferred lower death risk in HPV-positive (hazard ratio (HR) = 0.85, p < 0.001) and negative disease (HR = 0.87, p < 0.001) when controlling for age, sex, race, comorbidities, insurance, treatment facility, and income. In the largest cohort of CUP to date, we report a survival benefit in primary tumor detection regardless of HPV status. Groups with higher persistent CUP rates, including non-white, female, HPV-negative, and low income patients, may benefit from increased diagnostic workup to improve detection and treatment. [ABSTRACT FROM AUTHOR]