Radiotherapy-Induced Salivary Hypofunction: An Update on the Preventive Mechanisms

Abstract

The saliva is a fluid of extreme importance in the maintenance of oral homeostasis, being present in several biologic processes. It is composed in almost its totality by water and electrolytes, besides proteins such as immunoglobulins and mucins. This fluid acts in the lubrication of the mucosa, digestion, phonation, gustation, neutralization of acid components and in the immune systems through antimicrobial peptides against bacteria, fungi and viroses [1-5]. Hyposalivation is characterized by the decrease in the capacity of the salivary glands to secrete saliva, and xerostomia is defined as the subjective sensation of oral dryness. Such alterations can be caused by drugs, systemic diseases, head and neck radiotherapy, among other reasons [6]. Patients affected by salivary dysfunctions tend to show an atrophic oral mucosa, as well as symptoms such as dysphonia, dysphagia, oral burning sensation and palate alterations. There is increased risk to oral candidiasis, caries lesions and periodontal alterations [7-9]. The diminished bactericidal effect of saliva favors the increase of population of the microorganisms responsible for these diseases [8,10]. Head and neck radiotherapy is one of the main causes of salivary dysfunction [11,12]. The major salivary glands are usually included in the radiation portals due to the fact that they reside close to primary tumor sites and lymphatic chains of the head and neck region and frequently have their function impaired resulting in hyposalivation and xerostomia [11,13-15]. Among the radiotherapy methods most employed in head and neck region, conventional 2D radiotherapy (RC) is the one that presents the most significant side effects on the glandular tissue. Intensity-modulated radiotherapy (IMRT) and three dimensional conformal radiotherapy (3DCRT) reduce the radiation dose on the health structures close to the tumor and, consequently, the toxicity caused by the ionizing radiation [13,1620]. The salivary glands are extremely sensitive to ionizing radiation, presenting structural alterations which cause changes in salivary flow and composition [21]. These alterations are dose-dependent and can be irreversible [21,22]. Permanent hyposalivation is frequently associated to doses of ≥50 Gy, usually used for head and neck cancer treatment [23].