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.
This study aims to examine the relationship between race and rural-urban context in head and neck cancer (HNC) survival and determine factors that potentially drive this disparity.
Using the National ...Cancer Database from 2004 to 2015, we identified a retrospective cohort of 146,256 patients with HNC. Kaplan-Meier survival curves and the Cox proportional hazards regression were used to calculate adjusted HRs.
Median survival by patient subgroup was as follows: White urban 67 months; 95% confidence interval (CI), 66.0-67.9, White rural (59.1 months; 95% CI, 57.2-60), Black urban (43.1 months; 95% CI, 41.1-44.5), and Black rural (35.1 months; 95% CI, 31.9-39.0). The difference in 5-year survival, stratified by rural-urban context, was greater among Black patients Δ restricted mean survival time (ΔRMST) 0.18; 95% CI, 0.10-0.27 than White patients (ΔRMST 0.08; 95% CI, 0.06-0.11). In the univariate Cox proportional hazards analysis with White urban patients as reference group, Black rural patients had the worst survival (HR, 1.45; 95% CI, 1.43-1.48;
< 0.001), followed by Black urban patients (HR, 1.29; 95% CI, 1.28-1.30;
< 0.001), and White rural patients (HR, 1.08; 95% CI, 1.07-1.09;
< 0.001). This disparity persisted when controlling for demographic, socioeconomic, and clinical factors.
Black patients with HNC, specifically those living in rural areas, have decreased survival. Survival differences by rural-urban status are greater among Black patients than White patients.
We have shown that race and rural-urban status impact HNC survival outcomes. Our findings will help future researchers to better frame approaches to address this disparity.
•Mandibular osteoradionecrosis developed in 5.5% of head and neck cancer patients.•Smoking at the time of RT and pre-RT tooth extraction were clinical risk factors.•The use of 3D-conformal RT vs ...intensity-modulated RT was an additional risk factor.•Modifiable risk factors should be minimized.
To evaluate the incidence of, and risk factors associated with, mandibular osteoradionecrosis (MORN) following radiation therapy (RT) for oral cavity and oropharyngeal cancers.
Patient and treatment records of 252 consecutive patients with oral cavity or oropharynx cancers treated with RT by a single radiation oncologist at a high volume academic institution from August 2009 to December 2015 were retrospectively reviewed. A Cox regression model was used to assess factors associated with the development of MORN. RT dosimetry was compared between patients with MORN and a matched cohort of patients without MORN.
MORN developed in 14 patients (5.5%), occurring 3–40 (median 8) months post-RT. Factors associated with MORN on univariable analysis included primary diagnosis of oral cavity vs oropharynx cancer (hazard ratio HR: 3.0, p=0.04), smoking at the time of RT (HR: 3.1, p=0.04), mandibular invasion of the primary (HR: 3.7, p=0.04), pre-RT tooth extraction (HR: 4.52, p=0.01), and treatment with 3D-conformal RT vs intensity-modulated RT (HR: 5.1, p=0.003). On multivariable analysis, pre-RT tooth extractions and RT technique remained significant. A dosimetric comparison between patients with and without MORN showed no significant differences.
The incidence of MORN is low in the modern era at a high volume academic center. Modifiable risk factors including pre-RT tooth extractions, smoking, and RT technique are associated with MORN, and the risk should be minimized with appropriate dental evaluation and treatment, smoking cessation efforts, and the use of intensity-modulated RT.
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