While smoking is associated with worse outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), the magnitude of this association is unclear given the heterogenous smoking definitions ...and outcomes. Our objective was to investigate the association between smoking, survival, and recurrence in HPV-related OPSCC using multiple smoking metrics reported in the literature.
This was a retrospective cohort study of 375 adults with p16+ OPSCC undergoing surgical resection (n = 272) or definitive chemoradiation (n = 103) at a tertiary academic institution from 2006 to 2017. The primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and recurrence. We used multiple smoking metrics commonly cited in previous studies, including ever versus never smokers, current versus former/never smokers, ≤10 versus >10 pack-year, ≤20 versus >20 pack-year, and continuous pack-year.
There were 375 patients, median age 58 years, with 326 (87%) males, and median follow-up of 52 months. Of all smoking metrics, >20 pack-year history was the strongest predictor of both OS (HR 2.24, 95% CI: 1.19–4.20) and DFS (HR 1.67, 95% CI: 1.04–2.66) on univariable and multivariable analysis after adjusting for age, overall stage, and comorbidities. Patients with >20 pack-year smoking history were also more likely to have recurrence (HR 1.59, 95% CI: 0.95–2.67) after adjusting for overall stage.
Heavier smoking >20 pack-years was the strongest smoking metric associated with 2-times worse survival and recurrence. Our findings suggest that >20 pack-year smoking history may be a more useful cutoff for risk stratification models but requires further validation.
Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the ...interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case–control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making < $ 20,000/year OR 5.11 (3.61–6.61) compared to household incomes > $ 50,000/year OR 2.47 (1.69–3.25); p interaction < 0.001. Current drinking was more strongly associated with SCCHN in household incomes < $ 20,000 OR 2.91 (2.05–3.78) compared to > $50,000/year 1.28 (0.97–1.58); p interaction < 0.001. Current drinkers with less than high school education or income < $20,000 had nearly threefold odds of never-drinkers in the same SES category OR 2.91 (2.05–3.78); 2.09 (1.39–2.78), respectively. Our results suggest that the relationship of smoking and alcohol use may be stronger among those of lower SES.
•We found a significant association between markers of oral health and survival.•This association was most pronounced for sites closer to dentition, and present in cases as well as controls.•Oral ...health may represent a proxy for wellness or unexamined social determinants of health.•It may also have a direct effect on tumor biology or the immune response.
Poor oral health has emerged as a risk factor for squamous cell carcinoma of the head and neck (HNSCC) but its impact on survival has not been examined. We sought to estimate the impact of oral health indicators on survival in a population-based HNSCC cohort.
Cases (n=1381) and age-, sex- and race-matched controls (n=1396) were participants in the Carolina Head and Neck Cancer Epidemiologic Study (CHANCE). Vital status was determined via linkage with the National Death Index. Survival was considered at 5years post-diagnosis or study-enrollment for controls. Oral health was assessed using self-reported indicators including frequency of routine dental exams and tooth brushing. We used Kaplan-Meyer analyses and Cox regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI).
Routine dental visits during the preceding 10years were associated with decreased mortality risk (>10 visits: HR=0.6, 95% CI=0.4–0.8) after adjusting for confounders. This effect was most pronounced for oral cavity cancer—(e.g., >10 visits: HR=0.4, 95% CI=0.2–0.9). Dental visits were also positively associated with survival among controls. No other routine health screening (e.g., eye exams) was associated with survival.
We found significant associations between markers of oral health and survival among both HNSCC cases and controls. This association was most pronounced for sites closer to the dentition. Oral health may have a direct effect on tumor biology due to the associated immune or inflammatory response. It may also represent a proxy for wellness or unmeasured social determinants of health.
The choice of perioperative antibiotics for head and neck oncologic surgery is the subject of significant controversy. Given the ever-increasing number of antibiotic options available, as well as the ...growing problem of antibiotic resistance, there is a need for renewed research on this important topic. In their recent publication, Langerman and colleagues explore the relationship between antibiotic choice, surgical site infections, and antibiotic-induced complications in patients undergoing total laryngectomy. They demonstrate wide variability in antibiotic regimens among patients undergoing total laryngectomy, as well as an association between increased risk of surgical site infections and clindamycin use. This study addresses a controversial subject affecting the daily care of patients with head and neck cancer, and the findings have the potential to significantly affect management. It also highlights the strengths and inherent limitations of an administrative data approach to head and neck cancer clinical research.
Abstract
Previous studies have suggested a “J-shaped” relationship between body mass index (BMI, calculated as weight (kg)/height (m)2) and survival among head and neck cancer (HNC) patients. ...However, BMI is a vague measure of body composition. To provide greater resolution, we used Bayesian sensitivity analysis, informed by external data, to model the relationship between predicted fat mass index (FMI, adipose tissue (kg)/height (m)2), lean mass index (LMI, lean tissue (kg)/height (m)2), and survival. We estimated posterior median hazard ratios and 95% credible intervals for the BMI-mortality relationship in a Bayesian framework using data from 1,180 adults in North Carolina with HNC diagnosed between 2002 and 2006. Risk factors were assessed by interview shortly after diagnosis and vital status through 2013 via the National Death Index. The relationship between BMI and all-cause mortality was convex, with a nadir at 28.6, with greater risk observed throughout the normal weight range. The sensitivity analysis indicated that this was consistent with opposing increases in risk with FMI (per unit increase, hazard ratio = 1.04 (1.00, 1.08)) and decreases with LMI (per unit increase, hazard ratio = 0.90 (0.85, 0.95)). Patterns were similar for HNC-specific mortality but associations were stronger. Measures of body composition, rather than BMI, should be considered in relation to mortality risk.
Our goal was to demonstrate that lymphatic drainage fluid (lymph) has improved sensitivity in quantifying postoperative minimal residual disease (MRD) in locally advanced human papillomavirus ...(HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) compared with plasma, and leverage this novel biofluid for patient risk stratification.
We prospectively collected lymph samples from neck drains of 106 patients with HPV (+) OPSCC, along with 67 matched plasma samples, 24 hours after surgery. PCR and next-generation sequencing were used to quantify cancer-associated cell-free HPV (cf-HPV) and tumor-informed variants in lymph and plasma. Next, lymph cf-HPV and variants were compared with TNM stage, extranodal extension (ENE), and composite definitions of high-risk pathology. We then created a machine learning model, informed by lymph MRD and clinicopathologic features, to compare with progression-free survival (PFS).
Postoperative lymph was enriched with cf-HPV compared with plasma (P < 0.0001) and correlated with pN2 stage (P = 0.003), ENE (P < 0.0001), and trial-defined pathologic risk criteria (mean AUC = 0.78). In addition, the lymph mutation number and variant allele frequency were higher in pN2 ENE (+) necks than in pN1 ENE (+) (P = 0.03, P = 0.02) or pN0-N1 ENE (-) (P = 0.04, P = 0.03, respectively). The lymph MRD-informed risk model demonstrated inferior PFS in high-risk patients (AUC = 0.96, P < 0.0001).
Variant and cf-HPV quantification, performed in 24-hour postoperative lymph samples, reflects single- and multifeature high-risk pathologic criteria. Incorporating lymphatic MRD and clinicopathologic feature analysis can stratify PFS early after surgery in patients with HPV (+) head and neck cancer. See related commentary by Shannon and Iyer, p. 1223.
There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, ...with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.
What's new?
Folate is essential to DNA synthesis and repair, suggesting that folate deficiency, in disrupting normal DNA processes, may facilitate the development of certain cancers, including oral and pharyngeal cancer (OPC). The relationship between folate intake and risk of OPC, however, is unclear. In this analysis of data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, high levels of folate intake were found to be inversely associated with overall OPC risk. The association was strongest for cancer of the oral cavity. Risk of OPC was highest among heavy alcohol drinkers with low folate levels.
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual‐level pooled data from ten case‐control studies (5959 cases and 12,248 controls) ...participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non‐alcohol energy‐adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40–0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54–0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large‐scale pooled analysis suggest that, although in the presence of between‐study heterogeneity, a greater intake of fiber may lower HNC risk.
What's new?
Higher intake of fruit and vegetables is thought to lower the risk of HNCs. These foods are rich in phytochemicals and vitamins, but could dietary fiber also play a role in this protective effect? In this analysis, the authors pooled data from 10 separate studies to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Their results suggest that a greater intake of fiber may indeed lower HNC risk.
•Oral tongue squamous cell carcinoma (OTSCC) rates are increasing in young patients.•We examined a matched cohort of young and older OTSCC patients at our institution.•Younger patients were more ...likely to be female and to abstain from tobacco.•Younger OTSCC patients were significantly more likely to recur at 3 years.•There was no significant difference in overall survival.
The incidence of oral tongue squamous cell carcinoma (OTSCC) in younger adults has rapidly increased over the past two decades. While tobacco and alcohol use may be less likely to cause these tumors, it remains controversial whether differences also exist in their prognosis. Our aim is to examine the risk factors for cancer among young (<45 years old) OTSCC patients at our institution, and to compare their recurrence and survival with older patients in a matched cohort.
All OTSCC patients seen at our institution between 2000 and 2015 were reviewed. Patients under 45 who with sufficient treatment information were matched 1:1 on race, T-stage, and N-stage with patients 45 and older. Three-year recurrence and survival were determined in stratified and adjusted Cox regression models.
Of 397 OTSCC patients were seen at our institution, 117 (29%) were less than 45 years old. Younger patients were significantly more likely to be female, (50% vs. 39%; p = 0.04) and to abstain from tobacco (51% vs. 39%; p < 0.01). Young patients in the matched cohort were significantly more likely to have a recurrence (HR 3.9 95% CI 1.4–10.5). There was no difference in overall survival.
Younger OTSCC patients in a matched cohort were more likely to recur within 3 years, although there was no difference in overall mortality. Differences in risk factors and recurrence between older and younger patients suggest that some cancer among younger patients may be distinct from traditional OTSCC.
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