Impacto de fatores clínicos de prognóstico e biomarcadores salivares na qualidade de vida de pacientes com câncer de cabeça e pescoço: Um estudo prospectivo

Abstract

Head and neck cancer (HNC) has high incidence rates and contributes significantly to an increase in the mortality and morbidity statistics worldwide. Most of the cases are diagnosed late, thus requiring combined antineoplastic treatments that often impact the patient’s health related quality of life (HRQoL) for having adverse effects, including salivary changes. Objective: This study aimed to (i) evaluate the impact of clinical factors on the HRQoL of HNC patients; (ii) measure their salivary concentration of total proteins (TP), uric acid (UA), and salivary immunoglobulins (IgA and IgG); and further associate these outcomes with the clinical parameters of the patients. Material and Methods: This was a prospective longitudinal study with a sample of 85 individuals diagnosed with HNC and treated in reference cancer hospitals. The study subjects answered the validated Brazilian version of the University of Washington QoL questionnaire (UWQOL) before (phase 1 – P1) and during (phase 2- P2) antineoplastic treatment. Salivary analysis was performed with 45 participants from the sample. Clinical prognostic parameters of the patient (sex, age group, harmful habits) and of the lesion (type of neoplasia, anatomical site, T- tumor size, N-lymph node metastasis, M-distant metastasis, clinical staging and treatment modality) were obtained from medical records. Saliva samples were collected at P1 and P2. The stimulated saliva samples were placed in polypropylene tubes and kept at 4°C. Salivary analysis was performed in triplicate using 96-well microplates and four microliters of saliva were placed in each well. Enzymatic detection kits (LABTEST®) were used for colorimetric identification and quantification through spectrophotometry. In the first analysis, the data were analyzed using descriptive statistics, Wilcoxon test and multiple logistic regression (p<0.05), while in the second analysis, Mann-Whitney, Kruskal-Wallis and Wilcoxon tests were used, with p<0.05 considered significant. Results: Men were mostly affected by HNC (n=62; 73%), with a mean age of 63.22 ± 1.68 years. There was a significant difference in the total QoL score between P1 (770.41 ± 220.94) and P2 (568.98 ± 211.40) (p<0.001). The scores for the domains appearance, fitness, recreation, swallowing, chewing, taste and saliva were significantly lower at P2, indicating a worsening in the patients' QoL after the start of treatment. The variables age (OR=1.04; 95% CI: 1.01-1.07), smoking and alcoholism (OR=4.10; 95% CI: 1.17- 14.36) were associated with a worse QoL at P1. Larger tumors (T3 and T4) were associated with a worse QoL at both P1 (OR=3.47, 95% CI: 1.22-9.81) and P2 (OR=4.04; 95% CI: 1.41-11.60). The second part of the study was carried out to determine the salivary concentrations of relevant biomarkers in HNC patients. While there was no significant reduction in TP concentration between P1 (9.88 mg/ml) and P2 (7.52 mg/ml), (p=0.092), a significant association of TP with the presence of lymph node metastasis (N1-N3) was found at P2 (p=0.048). A significant reduction in UA levels was observed between P1 (56.53 μg/ml) and P2 (30.80 μg/ml) (p<0.001). There was no significant reduction in IgA concentration between P1 (0.56 mg/ml) and P2 (0.56 mg/ml) (p=0.307). On the other hand, IgA levels were found to be significantly associated with the patient's sex at P1 (p=0.046), with the highest concentrations observed among females. In addition, there was also a significant association of IgA with the tumor size at P2 (p=0.047). Lastly, no significant reduction in IgG concentration was detected between P1 (11.03 mg/ml) and P2 (11.03 mg/ml) (p=0.726); however, there was a significant association of IgG with the anatomical site of the lesion at P1 (p=0.045). Conclusion: Aging, smoking and alcoholism habits as well as larger tumors are clinical factors which significantly impact the HRQoL of HNC patients. It is concluded that the antineoplastic treatment for HNC induces salivary alterations and decreases the antioxidant activity of saliva.