**1. Introduction**

It is well recognized that the incidence of cancer, the second leading cause of death, globally, is increasing, an ongoing major burden of disease and public health burden, World-wide. While there were 14.1 million cancer cases reported in 2012, the World Health Organization (WHO) estimated about 1 in 6 deaths is due to cancer, with 9.6 million such deaths reported in 2018. In the United States, today, cancer is the second leading, after heart disease, cause of death amongst men and women, with over 1 million new cases diagnosed, annually [1].

Despite a reduction in tobacco consumption and the significant modern advancements in medicine, the number of new cancer cases, per year, is projected to rise to 22.2 million by 2030 [1]. Cancers, often squamous cell carcinomas/neoplasms, that involve the oral cavity, nostrils, paranasal sinuses, naso−/oro−/hypo-pharynx,

larynx, and the salivary glands, are commonly/collectively (despite their heterogeneity) termed head and neck cancers (HNC), which, together are responsible for nearly 200,000 deaths, a year, World-wide [2]. In the United States alone, HNC represent 4–5% of all cancers, and in Europe, HNC are the sixth most common group of cancers [3].

Besides the alarming incidence and mortality rates, HNC suffer a relatively poor prognosis, overall, whether due to delays in diagnosis, staging, treatment, particulars of the tumor site, onset, type of symptoms and/or efficacy of therapies, to mention a few. Such factors further contribute to permitting the progress and upstaging of the malignant tumor(s) which eventually result in enfeebled survival, despite the application of novel or advanced intensive therapeutic regimens. Briefly, treatment, often a multi-disciplinary case-specific approach, can employ chemo−/radio−/immune-therapy, surgery, or combinatorial strategies [4].

Herein, radiotherapy (RT), whether radical or prophylactic, remains a mainstay of HNC treatment, especially in light of modern improvements in precisely targeting and delivering the required radiation doses to the tumor, thereby allowing additional sparing of normal/healthy surrounding tissue(s), greatly reducing side or adverse effects of radiation, and consequently improving the quality of life (QoL) of patients as well as their families [5–8]. IMRT (intensity-modulated radiotherapy), VMAT (volumetric modulated arc therapy) and particle (ion-based) therapy are perhaps fine examples of modern high-precision RT [7].

RT, in general, aims to realize *localized* destruction and control of the target tumor (−cells) and halt of the reproductive potential, while minimizing toxicity onset. Specifically, high-energy radiation is deposited, causing DNA strands to break thereby damaging the cell genome either directly or indirectly (via freeradical production) and subsequently resulting in apoptosis, mitotic cell death, and tissue hypoxia, through different cascades and processes [5, 7]. Depending on the radiation dose and tissue turnover, amongst other factors, RT can almost always be expected to result in a range of side effects, of which some are reversible and others are irreversible (**Figure 1**). Indeed, HNC and oral squamous cell carcinoma (OSCC) patients receiving RT often experience pain, taste disturbances, difficulties in mastication and deglutition (swallowing) and suffer from mucositis, fungal infections, dental decay, alterations in speech, all of which are mainly due to or linked to salivary gland dysfunction which in turn results in hyposalivation and xerostomia [9–12].

Herein, xerostomia, a dry mouth sensation, is one of the main complications and complaints for HNC patients receiving RT, mainly as a sequela of the un-avoidable damage to the parotid and sub-mandibular glands (both produce over 80% of saliva) anatomically located with the radiation zone [8, 12]. Inflammation, fibrosis, atrophy and the reduced wound healing response, *i.e.* reparative and regenerative capacity of the glands, mainly due to lack of *functional* salivary gland stem/progenitor cells post-irradiation, render the *inevitable* radiotherapy-induced salivary gland damage and dysfunction, whether occurring early or late, a significant impediment to the QoL and survival of HNC and OSCC patients [10, 13, 14].

Therefore, besides modern advancements in radiation engineering technologies, ample pharmacological and pharmaceutical solutions have been explored [14]. Accumulating knowledge in understanding underlying signaling pathways, cellular and tissue responses, spatio-temporally, fuel the continuing efforts aimed to explore, develop and translate novel solutions to support in the prevention (and treatment of) radiation-induced side-effects and damage of salivary glands, a main focus of this chapter, designed to provide the *clinical* reader with a summary of relevant literature and recent innovative developments in salivary gland radioprotection and potential salivary gland repair, post-RT.

*Salivary Gland Radio-Protection, Regeneration and Repair: Innovative Strategies DOI: http://dx.doi.org/10.5772/intechopen.94898*

**Figure 1.**

*Head and neck cancers regions and irradiation intensity risk during HNC radiotherapy.*
