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Objectives: Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC)., Methods: Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors., Results: Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone., Conclusions: Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status., Level of Evidence: 3 Laryngoscope, 134:2243-2251, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To describe swallowing and feeding-tube outcomes in patients with high-risk oropharyngeal cancer treated with trimodality therapy (TMT), including transoral robotic surgery (TORS) and adjuvant chemoradiotherapy., Methods: A chart review was conducted on patients with HPV+ OPSCC receiving TMT with TORS at an academic medical center from March 2010 to March 2021. Data collected included demographics, treatment, feeding tube placement, functional oral intake scale (FOIS) scores, and swallowing-language pathology (SLP) evaluations., Results: A total of 255 patients met selection criteria (mean age 61 years, 88% male). Following intraoperative nasogastric tube (NG) placement, 31% remained NG tube dependent after 3 weeks. A gastrostomy tube was placed in 19% of patients, and at 1 year after end-of-treatment (EOT), 3.5% overall remained tube-dependent. Mean FOIS scores were 6.9 (SD = 0.3) at pre-operative visit, 2.6 (1.8) at first post-operative visit, and 5.5 (1.5) after EOT. In the subset of patients with follow-up longer than 2 years (n = 118), the mean FOIS was 6.1 (SD = 1.3) at most recent visit. Clinical signs of aspiration/penetration were suspected on SLP evaluation in 18% of patients. These patients were subsequently evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) and/or barium swallow study, which confirmed signs of aspiration in 2.7% of patients overall. Delayed NG tube removal after 3 weeks was predictive of (1) gastrostomy tube requirement and (2) clinical signs of aspiration on an SLP visit after EOT., Conclusions: Favorable functional and feeding-tube outcomes are demonstrated in patients with HPV-associated OPSCC undergoing TMT. In this single-institution study, we found low rates of long-term feeding tube dependence and high median FOIS following treatment. Review of routine SLP visits provides a detailed and easily accessible means for assessing swallowing function in this cohort., Level of Evidence: 4 Laryngoscope, 133:3013-3020, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Management of the neck in laryngeal squamous cell carcinoma (LSCC) is essential to oncologic control and survival. We aim to describe patterns and rates of clinical/pathologic lymph node disease, elective neck dissection (END), and occult lymph node metastasis (LNM) in patients with surgically-managed LSCC., Methods: Retrospective cohort study of patients in the National Cancer Database (NCDB) diagnosed with LSCC between January 2004 and December 2016 who underwent primary surgery., Results: Seven thousand eight hundred and seventy-six patients met inclusion criteria. For cN0 patients, the rates of END and occult LNM both increased with tumor stage and were highest for supraglottic tumors. Predictors of occult LNM included supraglottic site, pathologic T3 and T4 stage, positive margins, and presence of lymphovascular invasion (p < 0.05)., Conclusions: The propensity for cervical LNM in surgically-managed LSCC varies based on primary tumor site and stage, and a variety of disease factors increase risk of occult LNM., (© 2023 Wiley Periodicals LLC.)

Introduction: Management of the neck in oral cavity squamous cell carcinoma (OCSCC) is essential to oncologic control and survival. The rates of lymph node metastasis (LNM) vary based on oral cavity tumor site and stage and influence treatment decisions. The aim of this paper was to describe clinical LNM for different tumor subsites and stages of surgically managed OCSCC., Methods: We conducted a retrospective analysis of 25,846 surgically managed OCSCC patients from the National Cancer Database (NCDB) stratified by tumor subsite and clinical T-stage. For cN + patients, rates of pathologic LNM and absence of pathologic LNM were determined. For cN0 patients, outcomes included the rates of elective neck dissection (END) and occult LNM and predictors of occult LNM determined by a multivariable logistic regression model., Results: A total of 25,846 patients (59.1% male, mean age 61.9 years) met inclusion criteria with primary tumor sites including oral tongue (50.8%), floor of mouth (21.2%), lower alveolus (7.6%), buccal mucosa (6.7%), retromolar area (4.9%), upper alveolus (3.6%), hard palate (2.7%), and mucosal lip (2.5%). Among all sites, clinical N+ rates increased with T-stage (8.9% T1, 28.0% T2, 51.6% T3, 52.5% T4); these trends were preserved across subsites. Among patients with cN + disease, the overall rate of concordant positive pathologic LNM was 80.1% and the rate of discordant negative pathologic LNM was 19.6%, which varied based on tumor site and stage. In the overall cohort of cN0 patients, 59.9% received END, and the percentage of patients receiving END increased with higher tumor stage. Occult LNM among those cN0 was found in 25.1% of END cases, with the highest rates in retromolar (28.8%) and oral tongue (27.5%) tumors. Multivariable regression demonstrated significantly increased rates of occult LNM for higher T stage (T2 OR: 2.1 [1.9-2.4]; T3 OR: 3.0 [2.5-3.7]; T4 OR: 2.7 [2.2-3.2]), positive margins (OR: 1.4 [1.2-1.7]), and positive lymphovascular invasion (OR: 5.1 [4.4-5.8])., Conclusions: Management of the neck in OCSCC should be tailored based on primary tumor factors and considered for early-stage tumors., (© 2023 S. Karger AG, Basel.)

Importance: Cetuximab-based and carboplatin-based chemoradiotherapy (CRT) are often used for patients with locally advanced head and neck cancer who are ineligible for cisplatin. There are no prospective head-to-head data comparing cetuximab-based and carboplatin-based regimens for radiosensitization., Objective: To compare survival with cetuximab-based and carboplatin-based CRT in locally advanced head and neck squamous cell carcinoma (HNSCC)., Design, Setting, and Participants: This cohort study included US veterans who received a diagnosis of HNSCC between January 2006 and December 2020 and were treated with systemic therapy and radiation. Data cutoff was March 1, 2022 and data analysis was conducted from April-May 2022., Exposures: Cisplatin, cetuximab, or carboplatin-based systemic therapy as captured in VA medication data and cancer registry., Main Outcomes and Measures: Overall survival by systemic therapy was estimated using Kaplan-Meier methods. We used propensity score and inverse probability weighting to achieve covariate balance between cetuximab-treated and carboplatin-treated patients and used Cox regression to estimate cause-specific hazard ratios of death associated with carboplatin vs cetuximab. We also performed subgroup analyses of patients with oropharynx vs nonoropharynx primary sites., Results: A total of 8290 patients (median [IQR] age, 63 [58-68] years; 8201 men [98.9%]; 1225 [15.8%] Black or African American and 6424 [82.6%] White individuals) with nonmetastatic HNSCC were treated with CRT with cisplatin (5566 [67%]), carboplatin (1231 [15%]), or cetuximab (1493 [18%]). Compared with cisplatin-treated patients, patients treated with carboplatin and cetuximab were older with worse performance status scores and higher comorbidity burden. Median (IQR) overall survival was 74.4 (22.3-162.2) months in patients treated with cisplatin radiotherapy (RT), 43.4 (15.3-123.8) months in patients treated with carboplatin RT, and 31.1 (12.4-87.8) months in patients treated with cetuximab RT. After propensity score and inverse probability weighting, carboplatin was associated with improved overall survival compared with cetuximab (cause-specific hazard ratio, 0.85; 95% CI, 0.78-0.93; P = .001). This difference was prominent in the oropharynx subgroup., Conclusions and Relevance: In this cohort study of a US veteran population with HNSCC undergoing treatment with CRT, almost a third of patients were ineligible to receive treatment with cisplatin and received cetuximab-based or carboplatin-based radiosensitization. After propensity score matching, carboplatin-based systemic therapy was associated with 15% improvement in overall survival compared with cetuximab, suggesting that carboplatin may be the preferred radiosensitizer, particularly in oropharynx cancers.

Objective: To assess the impact of sociodemographic factors on primary treatment choice (surgery vs radiotherapy) in patients with human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC)., Study Design: Retrospective analysis of the National Cancer Database., Setting: Data from >1500 Commission on Cancer institutions (academic and community) via the National Cancer Database., Methods: Our sample consists of patients diagnosed with HPV+ OPSCC from 2010 to 2015. The primary outcome of interest was initial treatment modality: surgery vs radiation. We performed multivariable logistic models to assess the relationship between treatment choice and sociodemographic factors, including sex, race, treatment facility, and insurance status., Results: Of the 16,043 patients identified, 5894 (36.7%) underwent primary surgery while 10,149 (63.3%) received primary radiotherapy. Black patients were less likely than White patients to receive primary surgery (odds ratio [OR], 0.80; 95% CI, 0.66-0.96). When compared with privately insured patients, those who were uninsured or on Medicaid or Medicare were also less likely to receive primary surgery (OR, 0.70 [95% CI, 0.56-0.86]; OR, 0.77 [95% CI, 0.65-0.91]; OR, 0.85 [95% CI, 0.75-0.96], respectively). Patients receiving treatment at an academic/research cancer program were more likely to undergo primary surgery than those treated at comprehensive community cancer programs (OR, 1.33; 95% CI, 1.14-1.56)., Conclusion: In this large sample of patients with HPV+ OPSCC, race and insurance status affect primary treatment choice. Specifically, Black and nonprivately insured patients are less likely to receive primary surgery as compared with White or privately insured patients. Our findings illuminate potential disparities in HPV+ OPSCC treatment.

Objectives/hypothesis: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct clinical entity with good prognosis, unique demographics, and a trend toward treatment deintensification. Patients with this disease may opt out of recommended postoperative radiation therapy (PORT) for a variety of reasons. The aim of this paper was to examine factors that predict patient refusal of recommended PORT in HPV-associated OPSCC, and the association of refusal with overall survival., Study Design: Retrospective population-based cohort study of patients in the National Cancer Database., Methods: We conducted a retrospective cohort study of patients in the National Cancer Database diagnosed with OPSCC between January 2010 and December 2015. We primarily assessed overall survival and the odds of refusing PORT based on demographic, socioeconomic, and clinical factors. Analysis was conducted using multivariable logistic regression and multivariable Cox proportional hazards model., Results: A total of 4229 patients were included in the final analysis, with 156 (3.7%) patients opting out of recommended PORT. On multivariable analysis, patient refusal of PORT was independently associated with a variety of socioeconomic factors such as race, insurance status, comorbidity, treatment at a single facility, and margin status. Lastly, PORT refusal was associated with significantly lower overall survival compared to receipt of recommended PORT (hazard ratio 1.69, confidence interval 1.02-2.82)., Conclusions: Patient refusal of recommended PORT in HPV-associated OPSCC is rare and associated with variety of disease and socioeconomic factors. PORT refusal may decrease overall survival in this population. Our findings may help clinicians when counseling patients and identifying those who may be more likely to opt out of recommended adjuvant therapy., Level of Evidence: 3 Laryngoscope, 132:339-348, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Sex differences in surgically treated HPV-associated oropharyngeal squamous cell carcinoma are not defined due to the low number of affected women. We explored the oncologic outcomes of men and women with p16-positive oropharyngeal squamous cell carinoma treated with primary surgery., Materials and Methods: Retrospective analysis of patients with HPV-related oropharyngeal cancer treated with surgery and pathology guided adjuvant therapy from 2007 to 2017. Primary end point was recurrence-free and overall survival., Results: Of 468 men (86.7%) and 72 women (13.3%), women presented more often with clinical N0 nodal disease (25% vs 12.2%). There were no differences in adverse pathologic features or T stage, although women were more likely to present with N0 disease (16.7% vs 10%), less N2 disease (6.9% vs 17.7%, p = 0.03), and more stage I disease (88.9% vs 75%). As a result, women were more likely to undergo surgery alone (30.6% vs 14.1%) while men were more likely to require adjuvant radiation therapy (47.2% vs 36.1%). Four women (5.6%) and 30 men (6.4%, p = 0.8) died during follow-up. Multivariate analysis controlling for age, sex, treatment, and pathologic stage demonstrated no differences in overall survival between men and women. There were no differences in recurrence-free or overall survival between men and women at two and five years., Conclusions: Although women undergoing transoral robotic surgery for HPV+ oropharyngeal squamous cell carcinoma may have less advanced disease, upfront surgery with pathology-guided adjuvant therapy produces similar oncologic results in men and women while accounting for disease burden., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patients with oropharyngeal cancer who undergo transoral robotic surgery (TORS) and have high-risk features generally receive adjuvant chemoradiotherapy or trimodality therapy (TMT). The notion that TMT leads to high toxicity is largely based on studies that included human papilloma virus (HPV)-negative cancers and/or nonrobotic surgery; we sought to describe outcomes in HPV-associated oropharyngeal squamous cell cancer (HPV + OPSCC) undergoing TORS-TMT., Methods: In consecutive patients with HPV + OPSCC receiving TMT at an academic center from 2010 to 2017, survival was estimated using Kaplan-Meier methodology, and toxicities were ascertained via chart review., Results: In our cohort of 178 patients, 5-year survival was 93.6%. Feeding tube rates were 25.8% at therapy completion and 0.7% at 1 year. Rates of grade ≥ 3 kidney injury, anemia, and neutropenia in cisplatin-treated patients were 2.7%, 3.4%, and 11.0%, respectively., Conclusions: Patients with HPV + OPSCC who underwent TORS-TMT had excellent survival and low rates of toxicity and feeding tube dependence. These outcomes compare favorably to historical cohorts treated with definitive chemoradiotherapy., (© 2021 Wiley Periodicals LLC.)

Background: Patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV-negative OPSCC., Methods: Retrospective analysis HPV-negative OPSCC patients who underwent TORS, neck dissection and pathology-guided adjuvant therapy (2005-2017)., Results: Fifty-six patients (91.1% stage III/IV) were included. Three-year overall survival, locoregional control, and disease-free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow-up 30.6 months, interquartile range 18.4-66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long-term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively., Conclusion: The TORS approach for resectable HPV-negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity., (© 2021 Wiley Periodicals LLC.)

Objective: Despite epidemiologic evidence that second primaries occur infrequently in HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma, recent recommendations advocate for elective contralateral palatine tonsillectomy. We aimed to study this discordance and define the necessary extent of up-front surgery in a large contemporary cohort with long-term follow-up treated with unilateral transoral robotic surgery. We hypothesized that second primaries are discovered exceedingly rarely during follow-up and that survival outcomes are not compromised with a unilateral surgical approach., Study Design: Retrospective cohort analysis., Setting: Tertiary care academic center between 2007 and 2017., Methods: Records for patients with p16-positive oropharyngeal squamous cell carcinoma of the tonsil and workup suggestive of unilateral disease who underwent ipsilateral transoral robotic surgery were analyzed for timing and distribution of locoregional recurrence, distant metastases, and second primary occurrence as well as survival characteristics., Results: Among 295 included patients, 21 (7.1%) had a locoregional recurrence; 17 (5.8%) had a distant recurrence; and 3 (1.0%) had a second primary during a median follow-up of 48.0 months (interquartile range, 29.5-62.0). Only 1 (0.3%) had a second primary found in the contralateral tonsil. The 2- and 5-year estimates of overall survival were 95.5% (SE, 1.2%) and 90.1% (SE, 2.2%), respectively, while the 2- and 5-year estimates of disease-free survival were 90.0% (SE, 1.8%) and 84.7% (SE, 2.3%)., Conclusion: Second primary occurrence in the contralateral tonsil was infrequent, and survival outcomes were encouraging with unilateral surgery. This provides a rationale for not routinely performing elective contralateral tonsillectomy in patients whose workup suggests unilateral disease.

Background: Some patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) do not receive guideline-recommended postoperative radiation therapy (PORT) following primary transoral robotic surgery (TORS)., Methods: Three-hundred and sixty-four patients with treatment-naïve, HPV-associated OPSCC were recommended to receive PORT based on clinicopathological features following TORS. Patients were stratified based on if they received PORT. Oncologic outcomes were compared., Results: The 3-year locoregional failure (LRF) was 32% in patients who did not receive PORT and 4% in patients who received PORT (P < .001). Despite increased LRF, avoiding PORT was not associated with increased 3-year distant metastasis rates (8% vs 4%, P = .56) or worse 3-year survival (95% vs 98%, P = .34). Recurrences in the surgery alone cohort varied between local and regional sites and were often successfully salvaged., Conclusions: Patients with HPV-associated OPSCC who do not receive indicated PORT have an increased risk of LRF but similar survival due to high salvage rates., (© 2020 Wiley Periodicals LLC.)

Objectives: (1) To estimate the association between neck dissection lymph node yield (LNY) and survival among patients with surgically treated human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). (2) To identify a clinically relevant quality metric for surgical treatment of HPV-related OPSCC., Study Design: Retrospective cohort study., Setting: National Cancer Database., Subjects and Methods: From the National Cancer Database, 4130 patients were identified with HPV-associated OPSCC treated with primary surgery from 2010 to 2016. Based on prior literature, an adequate neck dissection LNY was defined as ≥18 lymph nodes. To determine whether LNY is associated with survival, univariable and multivariable Cox proportional hazards regression was performed. Analysis was stratified by adjuvant therapy regimen., Results: A total of 2113 patients (51.2%) underwent surgery with or without adjuvant radiation (S ± RT), and 2017 patients (48.8%) underwent surgery with adjuvant chemoradiation. LNY ≥18 was associated with a 5-year survival benefit of 7.15% (91.7% for LNY ≥18, 84.5% for LNY <18, P = .004) for the S ± RT cohort on unadjusted survival analysis. For the S ± RT group, LNY ≥18 was associated with decreased hazard of death (hazard ratio, 0.45; 95% CI, 0.29-0.70; P < .001) after adjustment for patient characteristics, TNM staging, surgical margins, extranodal extension, and treating facility characteristics. For surgery with adjuvant chemoradiation, the adjusted hazard ratio estimate for LNY ≥18 was 0.64 (95% CI, 0.41-1.00), but the result was not statistically significant ( P = .052)., Conclusion: An adequate LNY from a neck dissection may affect survival when HPV-related OPSCC is treated with up-front surgery.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing dramatically and is conclusively linked to increasing rates of human papillomavirus (HPV) infection. HPV-related oropharyngeal cancers have been shown to occur in a unique demographic group and show favorable oncologic outcomes compared with HPV-negative OPSCC. There has been a paradigm shift in the treatment of early-stage OPSCC, with most patients now undergoing primary surgery in the United States. Transoral robotic surgery is associated with excellent oncologic and functional outcomes in the treatment of OPSCC and is increasingly being used for a broader range of oropharyngeal indications., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: While early epidemiologic studies ascribed increases in the incidence of human papillomavirus-associated oropharyngeal cancers to middle-aged patients, recent analyses have demonstrated an increasing median age of diagnosis. Treatment of patients older than 70 years is controversial as their inclusion in the practice-defining clinical trials has been limited and the survival benefit conferred by chemotherapy may be outweighed by treatment toxic effects., Objective: To assess the oncologic outcomes of older adults with human papillomavirus-associated oropharyngeal cancer who underwent upfront transoral robotic surgery and pathologic characteristics-guided adjuvant therapy in a large cohort of patients with close follow-up., Design, Setting, and Participants: A retrospective cohort analysis was conducted in a tertiary care academic medical center between January 1, 2010, and December 30, 2017. Patients aged 70 years or older at time of diagnosis with biopsy-proven and surgically resectable p16-positive oropharyngeal cancers were included. Data analysis was conducted from March 1 to June 1, 2020., Exposures: Transoral robotic surgery oropharyngeal resection and neck dissection with pathologic characteristic-guided adjuvant therapy., Main Outcomes and Measures: Three-year estimates of disease-specific survival, overall survival, and disease-free survival, as well as rates of adjuvant therapy (radiotherapy and chemoradiotherapy) and perioperative complications., Results: Seventy-seven patients were included (median age, 73.0; interquartile range, 71.0-76.0; range, 70-89 years); of these, 58 were men (75.3%). Perioperative mortality was 1.3% and the rate of oropharyngeal hemorrhage was 2.6%. Twenty-seven patients (35.1%) underwent postoperative radiotherapy and 20 patients (26.0%) underwent postoperative chemoradiotherapy. The median length of follow-up was 39.6 (range, 0.1-96.2) months, and the 3-year estimates of survival were 92.4% (95% CI, 82.4%-96.9%) for disease-specific survival, 90.0% (95% CI, 79.4%-95.0%) for overall survival, and 84.3% (95% CI, 73.4%-91.0%) for disease-free survival., Conclusions and Relevance: The findings of this cohort study suggest that transoral robotic surgery and pathologic characteristic-guided adjuvant therapy can provide beneficial survival outcomes, infrequent perioperative mortality, and, for most carefully selected older adults, obviate the need for chemotherapy.