Plasma catecholamines levels in oral and oropharyngeal cancer patients and their associations with clinicopathological variables and anxiety symptoms

Background: Catecholamines may regulate several biological effects resulting from chronic stress. Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamines secretion profile in head and neck cancer squamous cell carcinoma (HNSCC) patients and its association with clinicopathological and psychological variables. The present study investigated the pre-treatment plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in patients with oral and oropharyngeal SCC and patients with oral leukoplakia, as well as their associations with clinicopathological and biobehavior variables and anxiety symptoms. Patients and methods: A total of 71 patients with oral SCC, 22 patients with oropharyngeal SCC and 32 patients with oral leukoplakia were submitted to blood samples. Plasma levels of NE and E were measured by High Performance Liquid Chromatography with electrochemical detection (HPLC-ED) and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Differences in hormone levels among the groups were analyzed by ANOVA test. Univariate and multiple regression analyzes were performed to evaluate the associations of hormonal levels with clinicopathological, biobehavior and psychological variables. Results: Plasma NE and E concentrations were significantly higher in patients with oral and oropharyngeal cancer than oral leukoplakia patients (p<0.05). Oral SCC patients showed NE levels (462.03±47.53 pg/mL) about six times and nine times higher than patients with oropharyngeal SCC (74.46±12.52 pg/mL) and oral leukoplakia (51.69±6.28 pg/mL), respectively. Plasma NE and E levels were positively correlated in patients with oral SCC (p=0.0011), but not in the oropharyngeal SCC and oral leukoplakia groups. Multiple regression analyses showed that in oral SCC group single and joined with oropharyngeal SCC patients (HNSCC group), the history of high alcohol consumption was predictive for reduced plasma NE levels (oral SCC: β=-119.2, p=0.0296; HNSCC: β=-171.7, p=0.0002). In the cancer groups, the overall anxiety score measured by BAI was not significantly correlated to catecholamines levels (p>0.05). However, anxiety symptoms measures with BAI such as “hands trembling” (β=157.5, p=0.0377) and “heart pouding/rancing” (β=15.88, p=0.0441) were significantly associated with higher plasma E levels in HNSCC and oropharyngeal SCC groups, respectively. Sleep deprivation and worse sleep quality in the previous night of blood collection were predictive variables for elevated NE levels in oral leukoplakia. In this patient group, severe tobacco consumption (β=1.54, p=0.0051) and higher anxiety levels (β=7.16, p=0.0003) were independent predictors for higher plasma E levels. Conclusion: Oral and oropharyngeal cancer patients display a modulation of plasma NE and E secretion. Furthermore, systemic catecholamines levels in patients with head and neck cancer and potentially malignant disorders may be influenced by biobehavior and psychological factors. (AU)