Oral leukoplakia and risk of progression to oral cancer: A population-based cohort study

BACKGROUND: The 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\u27s decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression. METHODS: We 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. RESULTS: Compared 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. CONCLUSIONS: The 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

Recent advances of novel targeted therapy for squamous cell carcinoma of the head and neck

Targeted therapies have proven beneficial for patients suffering from a number of different malignancies, including cancers of the head and neck. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor has shown benefit in combination with radiation for untreated patients or as a single agent for patients with platinum resistant disease. Cetuximab is the only targeted agent currently approved by the Federal Drug Administration for the treatment of head and neck cancer. A number of other agents have shown promising initial results including intracellular tyrosine kinase inhibitors, agents targeting vascular endothelial growth factor receptor, as well as other classes of novel therapies. Some of the data supporting the use of targeted therapy, including agents not yet approved in head and neck cancer, will be presented in this review. As our understanding of the cancer cell signaling pathways and novel targeted agents increases, the potential for treatment with reduced toxicity and improved clinical outcomes will become a reality

Undertreatment of women with locoregionally advanced head and neck cancer.

BackgroundIt is difficult to predict whether a patient with head and neck cancer (HNC) is more likely to die of the cancer or another comorbidity. Competing event models can help to identify individual patients or groups of patients who may be undertreated or overtreated in clinical practice.MethodsPatients with HNC (n = 884), aged 18 to 85 years and diagnosed from 2000 to 2015 with stage II to IVB disease according to the seventh edition of the American Joint Committee on Cancer system, were identified. With a generalized competing event (GCE) model that controlled for age, sex, tumor site, surgical treatment, and Charlson Comorbidity Index (CCI), the association between these factors and the relative hazard for cancer mortality was determined. Logistic regression models were used to estimate the odds of receiving platinum-based chemoradiotherapy or a less intensive therapy, with adjustments made for age, sex, tumor site, CCI, stage, smoking, and alcohol abuse history.ResultsCompared with men, women had an increased relative hazard ratio for death from HNC versus other causes, which was reported as an adjusted ω+ ratio comparing women with men (ω+ ratio, 1.95; 95% CI, 1.09-3.49), even though they were less likely to receive intensive chemoradiotherapy than men (adjusted odds ratio, 0.69; 95% CI, 0.48-0.99).ConclusionsThese findings indicate that women in this cohort may be undertreated in clinical practice and potentially miss the opportunity for their HNC to be aggressively treated. This study supports the use of GCE models to identify patients who are potentially undertreated and may also help to guide future research in health disparities