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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.

IMPORTANCE Nasal obstruction is a common chief concern; however, a comprehensive standardized worksheet for evaluating nasal obstruction has not been developed. OBJECTIVE To evaluate the interrater reliability between staff surgeons and otolaryngology residents using a worksheet-based standardized nasal examination and to identify specific examination findings correlated with the Nasal Obstruction Symptom Evaluation quality-of-life score. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study conducted from June to July 2012 involved 50 adults presenting to an otolaryngology clinic at a tertiary care hospital. The patients were examined by 2 board-certified facial plastic surgeons and 2 otolaryngology residents. EXPOSURES The inferior turbinates, septum, and internal and external nasal valve narrowing and collapse were graded bilaterally from a scale of 0 to 3 with the aid of a standardized nasal anatomy worksheet. The findings were compared between the attending staff, residents, and the entire group. MAIN OUTCOMES AND MEASURES The Cohen κ coefficient for interrater reliability was calculated for each of the graded metrics. The Nasal Obstruction Symptom Evaluation scores were correlated with anatomic scores. RESULTS Of the 49 patients included in the final analysis, the mean age was 43.6 years (range, 21-82 years), and 31 were male (66.3%). Among all attending and resident examiners, a moderate to fair, statistically significant interrater reliability coefficient (P < .001) was observed in the following nasal anatomic measurements: left and right Cottle (κ = 0.582 [95% CI, 0.463-0.700] and κ = 0.580 [95% CI, 0.461-0.698], respectively), modified Cottle (κ = 0.491 [95% CI, 0.373-0.609] and κ = 0.560 [95% CI, 0.442-0.679], respectively), dynamic internal nasal valve collapse (κ = 0.204 [95% CI, 0.118-0.290] and κ = 0.232 [95% CI, 0.140-0.323], respectively), and inferior turbinate hypertrophy (κ = 0.252 [95% CI, 0.152-0.352] and κ = 0.235 [95% CI, 0.153-0.317], respectively). The trend of examination interrater reliability was similar for attending staff and the otolaryngology residents. The Nasal Obstruction Symptom Evaluation score correlated with the mean total anatomic worksheet score (Spearman ρ = 0.301; P = .048). CONCLUSIONS AND RELEVANCE Interrater reliability is high in both residents and attending staff for dynamic nasal airway examinations evaluating the internal and external nasal valves and for turbinate hypertrophy assessment. The total nasal anatomic score using a standardized worksheet correlates to patient-reported nasal-specific quality of life. LEVEL OF EVIDENCE NA.

IMPORTANCE Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors. OBJECTIVE To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021. MAIN OUTCOMES AND MEASURESPositivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites. RESULTSThe study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male [73.9%]; mean [SD] age, 59.5 [10.8] years) and 254 (33.1%) with CESC (mean [SD] age, 48.7 [14.1] years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio [aHR], 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8 + T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% [95% CI, 84.8%-99.9%] vs 45.8% [95% CI, 28.3%-74.1%]; HR, 0.10 [95% CI, 0.03-0.30]; P = .009). CONCLUSIONS AND RELEVANCEIn this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-posi...

BackgroundThe impact of close surgical margins on oncologic outcomes in HPV‐related oropharyngeal squamous cell carcinoma (HPV + OPSCC) is unclear.MethodsRetrospective case series including patients undergoing single modality transoral robotic surgery (TORS) for HPV + OPSCC at three academic medical centers from 2010 to 2019. Outcomes were compared between patients with close surgical margins (<1 mm or requiring re‐resection) and clear margins using the Kaplan–Meier method.ResultsNinety‐nine patients were included (median follow‐up 21 months, range 6–121). Final margins were close in 22 (22.2%) patients, clear in 75 (75.8%), and positive in two (2.0%). Eight patients (8.1%) recurred, including two local recurrences (2.0%). Four patients died during the study period (4.0%). Local control (p = 0.470), disease‐free survival (p = 0.513), and overall survival (p = 0.064) did not differ between patients with close and clear margins.ConclusionsPatients with close surgical margins after TORS for HPV + OPSCC without concurrent indications for adjuvant therapy may be considered for observation alone.

The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265–0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341–0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229–0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = −0.79, CI: −1.6, −0.03, p = 0.041; PFS: log (HR) = −0.78, CI: −1.4, −0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.

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IMPORTANCETumor histological factors that predict immunotherapy response in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are not well defined.OBJECTIVE To investigate the association between tumor grade and immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective cohort study, the medical records of 60 patients with recurrent or metastatic mucosal HNSCC treated with immune checkpoint inhibitors at Johns Hopkins Hospital between July 1, 2015, and January 22, 2020, were reviewed.EXPOSURES High-grade tumors (HGTs) vs low-grade tumors (LGTs) in recurrent or metastatic HNSCC. MAIN OUTCOMES AND MEASURESPatients were divided into 2 groups: those with LGTs (well differentiated and moderately differentiated) and those with HGTs (poorly differentiated). The main outcome was a clinically beneficial immunotherapy response, defined as complete response or partial response. Univariable and multivariable logistic regressions were conducted to calculate odds ratios for each variable's association with immunotherapy response. Survival differences were evaluated using Kaplan-Meier survival curves with multivariable Cox proportional hazards regression models. RESULTSThe 60 patients (35 with HGTs and 25 with LGTs) had a mean (SD) age of 64.6 (8.88) years; 51 were male (85%); and 38 were current or former smokers (63%). The oropharynx was the most common primary tumor site both in patients with HGTs (22 of 35; 63%) and those with LGTs (12 of 25; 48%). Bivariate analysis showed the proportion of patients having a beneficial response to immunotherapy was greater for patients with HGTs (12 of 35; 34.3%) than those with LGTs (2 of 25, 8.0%) (difference, 26.3%; 95% CI, 7.3%-45.3%). Upon multivariable analysis, patients with HGTs had 5.35-fold increased odds (95% CI, 1.04-27.37) of having a clinically beneficial response to immunotherapy. Among patients with available tumor genomic profiling data, the mean tumor mutational burden was greater for patients with HGTs (mean [SD], 8.6 [5.4] mut/Mb; n = 8) than patients with LGTs (mean [SD], 3.6 [1.1] mut/Mb; n = 4) (difference = 5.0 mut/Mb; 95% CI −1.4 to 11.4 mut/Mb; Cohen d = 1.2). CONCLUSIONS AND RELEVANCEIn this cohort study, tumor grade was independently associated with immunotherapy response in patients with recurrent or metastatic mucosal HNSCC. These findings highlight the potential role of tumor grade in predicting immunotherapy response in mucosal HNSCC.