Dataset Information

Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly.

ABSTRACT: Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages ?65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR ? 3 months, 24; 95% confidence interval (CI), 22-27; HR ? 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality.

SUBMITTER: Yanik EL

PROVIDER: S-EPMC4560597 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly.

Yanik Elizabeth L EL Katki Hormuzd A HA Silverberg Michael J MJ Manos M Michele MM Engels Eric A EA Chaturvedi Anil K AK

Cancer prevention research (Philadelphia, Pa.) 20150709 9

Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages ≥65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer regis ...[more]

PMID: 26159805

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Project description:BackgroundThe optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.MethodsWe conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of progression. Analyses included indirect standardization and unweighted or weighted Cox regression.ResultsCompared with the overall Kaiser Permanente Northern California population, oral cancer incidence was substantially elevated in oral leukoplakia patients (standardized incidence ratio = 40.8, 95% confidence interval [CI] = 34.8 to 47.6; n = 161 cancers over 22 582 person-years). Biopsied leukoplakias had a higher oral cancer risk compared with those that were not biopsied (adjusted hazard ratio = 2.38, 95% CI = 1.73 to 3.28). However, to identify a prevalent or incident oral cancer, the biopsy decision had low sensitivity (59.6%), low specificity (62.1%), and moderate positive-predictive value (5.1%). Risk of progression to oral cancer statistically significantly increased with the grade of dysplasia; 5-year competing risk-adjusted absolute risks were: leukoplakia overall = 3.3%, 95% CI = 2.7% to 3.9%; no dysplasia = 2.2%, 95% CI = 1.5% to 3.1%; mild-dysplasia = 11.9%, 95% CI = 7.1% to 18.1%; moderate-dysplasia = 8.7%, 95% CI = 3.2% to 17.9%; and severe dysplasia = 32.2%, 95% CI = 8.1%-60.0%. Yet 39.6% of cancers arose from biopsied leukoplakias without dysplasia.ConclusionsThe modest accuracy of the decision to biopsy a leukoplakia vis-à-vis presence or eventual development of oral cancer highlights the need for routine biopsy of all leukoplakias regardless of visual or clinical impression. Leukoplakia patients, particularly those with dysplasia, need to be closely monitored for signs of early cancer.

Project description:ImportanceLocoregional recurrence of oral cavity squamous cell carcinoma (OCSCC) continues to be a life-threatening and difficult clinical situation. Salvage surgery can result in significant morbidities, and survival following recurrence is poor.ObjectiveTo outline prognostic factors influencing overall survival (OS) following salvage surgery for OCSCC to guide management of treatment for patients with locoregionally recurrent disease.Design, setting, and participantsThe medical records of 293 patients presenting to the London Health Sciences Center with locoregionally recurrent OCSCC between October 5, 1999, and May 2, 2011, were retrospectively reviewed. The primary outcome was OS from salvage treatment to last follow-up or death. Univariate analyses were carried out using the Cox proportional hazards regression model. A recursive partitioning analysis was used to create risk groups based on prognosis. Analysis was conducted from December 8, 2015, to February 26, 2016.ResultsOf the 293 patients evaluated, 59 (20%) had recurrence identified after their initial OCSCC treatment; 39 (66%) were men, and the mean (SD) age at diagnosis was 62.2 (11.8) years. Thirty-nine (66%) of these patients underwent salvage surgery for locoregional recurrence with curative intent. Five-year OS from the time of salvage surgery was 43%. Recursive partitioning analysis identified 3 risk groups: (1) high risk (patients who received adjuvant chemoradiotherapy or radiotherapy after initial surgery) with 5-year OS rate of 10% (hazard ratio [HR], 9.41; 95% CI, 2.68-33.04), (2) intermediate risk (previous surgery alone, age ≥62 years) with a 5-year OS rate of 39% (HR, 2.95; 95% CI, 0.86-10.09), and (3) low risk (previous surgery alone, age <62 years) with 5-year OS rate of 74%.Conclusions and relevanceThis recursive partitioning analysis identified 3 prognostic groups in patients undergoing salvage surgery for recurrent OCSCC. The marked differences in survival between these groups should be taken into consideration when counselling and managing treatment for patients with locoregionally recurrent disease.

Project description:Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of malignant transformation compared with the more common localized leukoplakia. We hypothesized that the immune microenvironment and gene expression patterns would be distinct for proliferative leukoplakia compared with localized leukoplakia. We summarize key clinicopathologic features among proliferative leukoplakia and localized leukoplakia and compare cancer-free survival (CFS) between subgroups. We analyze immunologic gene expression profiling in proliferative leukoplakia and localized leukoplakia tissue samples (NanoString PanCancer Immune Oncology Profiling). We integrate immune cell activation and spatial distribution patterns in tissue samples using multiplexed immunofluorescence and digital image capture to further define proliferative leukoplakia and localized leukoplakia. Among N = 58 patients (proliferative leukoplakia, n = 29; localized leukoplakia, n = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; P < 0.01; 5-year CFS 46.8% and 83.6% among patients with proliferative leukoplakia and localized leukoplakia, respectively). CD8+ T cells and T regulatory (Treg) were more abundant among proliferative leukoplakia samples (P < 0.01) regardless of degree of epithelial dysplasia, and often colocalized to the dysplasia-stromal interface. Gene set analysis identified granzyme M as the most differentially expressed gene favoring the proliferative leukoplakia subgroup (log2 fold change, 1.93; P adj < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS (P adj < 0.01). Proliferative leukoplakia predicts a high rate of malignant transformation within 5 years of diagnosis. A prominent CD8+ T-cell and Treg signature along with relative PD-L1 overexpression compared with localized leukoplakia provides strong rationale for PD-1/PD-L1 axis blockade using preventative immunotherapy.SignificanceThis is the first in-depth profiling effort to immunologically characterize high-risk proliferative leukoplakia as compared with the more common localized leukoplakia. We observed a notable cytotoxic T-cell and Treg signature with relative overexpression of PD-L1 in high-risk proliferative leukoplakia providing a strong preclinical rationale for investigating PD-1/PD-L1 axis blockade in this disease as preventative immunotherapy.

Dataset Information

Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly.

Publications

Leukoplakia, Oral Cavity Cancer Risk, and Cancer Survival in the U.S. Elderly.

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