Objectives/Hypothesis
Literature examining long‐term survival in head and neck squamous cell carcinoma (HNSCC) with human papillomavirus (HPV) status is lacking. We compare 10‐year overall survival ...(OS) rates for cases to population‐based controls.
Study Design
Prospective cohort study.
Methods
Cases surviving 5 years postdiagnosis were identified from the Carolina Head and Neck Cancer Study. We examined 10‐year survival by site, stage, p16, and treatment using Kaplan‐Meier and Cox proportional hazard models. Cases were compared to age‐matched, noncancer controls with stratification by p16 and smoking status.
Results
Ten‐year OS for HNSCC is less than controls. In 581 cases, OS differed between sites with p16+ oropharynx having the most favorable prognosis (87%), followed by oral cavity (69%), larynx (67%), p16− oropharynx (56%), and hypopharynx (51%). Initial stage, but not treatment, also impacted OS. When compared to controls matched on smoking status, the hazard ratio (HR) for death in p16+ oropharynx cases was 1.5 (95% confidence interval CI: 0.7‐3.1) for smokers and 2.4 (95% CI: 0.7‐8.8) for nonsmokers. Similarly, HR for death in non–HPV‐associated HNSCC was 2.2 (95% CI: 1.7‐3.0) for smokers and 2.4 (95% CI: 1.4‐4.9) for nonsmokers.
Conclusions
OS for HNSCC cases continues to decrease 5 years posttreatment, even after stratification by p16 and smoking status. Site, stage, smoking, and p16 status are significant factors. These data provide important prognostic information for HNSCC.
Level of Evidence
2 Laryngoscope, 129:2506–2513, 2019
Background
The epidemiology of head and neck cancer (HNC) sites differ substantially. This study compares HNC incidence trends by site and demographic subgroups.
Methods
We used the U.S. Cancer ...Statistics Public Use Database to calculate HNC incidence rates per 100 000. We assessed trends with annual percent change (APC) longitudinally from 2001 to 2017.
Results
The oropharyngeal cancer incidence APC decreased from 4.38% (95% CI: 3.6, 5.1) to 2.93% (2.5, 3.3) in 2008 among White males. Oral cavity cancer incidence rose in Other race males (APC 2.5% 1.6, 3.36) and White females (APC: 0.96% 0.7, 1.2). Although decreasing (APC: −1.15% −1.48, −0.83), laryngeal cancer incidence remained disproportionately high among Black males.
Conclusions
Notable incidence trends occurred in non‐White groups at non‐oropharyngeal sites. With parity of smoking rates by race, differing sexual behaviors, and shifting demographics by race and sex, future studies of HNC trends should consider stratifying analyses to understand health disparities.
Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(−), and treatment typically involves surgical resection ± neck dissection, followed by radiation ...± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(−) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan–Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(−) non-mesenchymal OCSCC patients had far better survival compared to node(−) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(−) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.
Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 ...US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.
The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient ...stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry–based targeted proteomics assay based on internal standard–triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard–triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, NRF2 signaling intensity positively correlated with NRF2-activating mutations and with SOX2 protein expression. Protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus infection status. CDKN2A (p16) protein expression positively correlated with the human papilloma virus oncogenic E7 protein and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or formalin-fixed paraffin-embedded archived tissues in under 90 min.
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•Optimized data acquisition reduces cycle times for triggered PRM experiments.•PRM robustly quantifies NRF2 activation in cell lines and FFPE oral cavity tumors.•Detection of low-abundant immune checkpoints and HPV16 E7 from oropharyngeal tumors.•HPV(+) oropharyngeal cancers overexpress T-cell markers relative to HPV(−) cancers.
Optimized internal standard–triggered parallel reaction monitoring (OIS-PRM) reduces cycle times and increases sensitivity. OIS-PRM was applied with a custom peptide library to study protein markers of NRF2 signaling, HPV infection, and tumor-infiltrating immune cells. NRF2 activity was robustly quantified in cell lines and HNSCC FFPE tumors. Moreover, OIS-PRM detected HPV16 E7 and revealed increased T-cell marker and immune checkpoint proteins in HPV(+) compared to HPV(−) tumors.
Objectives/Hypothesis
To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV‐negative head and neck squamous cell ...carcinoma (HNSCC).
Study Design
Retrospective cohort study.
Methods
Data were examined from of a population‐based HNSCC study in North Carolina. Multivariable logistic regression and Cox proportional hazards models were used to assess racial disparities in stage at diagnosis and OS with sequential adjustment sets.
Results
A total of 340 black patients and 864 white patients diagnosed with HPV‐negative HNSCC were included. In the unadjusted model, black patients had increased odds of advanced T stage at diagnosis (OR 2.0; 95% CI 1.5–2.5) and worse OS (HR 1.3, 95% CI 1.1–1.6) compared to white patients. After adjusting for age, sex, tumor site, tobacco use, and alcohol use, the racial disparity persisted for advanced T‐stage at diagnosis (OR 1.7; 95% CI 1.3–2.3) and showed a non‐significant trend for worse OS (HR 1.1, 95% CI 0.9–1.3). After adding SES to the adjustment set, the association between race and stage at diagnosis was lost (OR: 1.0; 95% CI 0.8–1.5). Further, black patients had slightly favorable OS compared to white patients (HR 0.8, 95% CI 0.6–1.0; P = .024).
Conclusions
SES has an important contribution to the racial disparity in stage at diagnosis and OS for HPV‐negative HNSCC. Low SES can serve as a target for interventions aimed at mitigating the racial disparities in head and neck cancer.
Level of Evidence
4 Laryngoscope, 131:1301–1309, 2021
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