Previous editions of this book addressed the oral mucosa, the salivary glands and the teeth and mandible (i.e., jaw bone). This clinical approach is based on the LENT SOMA system that categorizes and grades various toxicities (Tables 1, 2, and 3), and does not differentiate between early and late adverse events. As evidence-based data on oral complications of cancer patients expanded, scales were published for specific oral complications. Several global scales are currently used. For example, the National Cancer Institute published an update for the Common Toxicity Criteria for Adverse Events (CTC-AE ver. 4.0) and a new version is expected in the near future. Selected items from the CTC-AE are presented in Table 4.

Additional scales are listed in the RTOC website.

In this edition, common oral complications will be presented, including oral mucosal alterations (late-mucosal injury and cGVHD), taste disorders, salivary gland dysfunctions, infections, neuropathy and chronic pain, complications of the dentition and periodontium, trismus and loss of elasticity, osteoradionecrosis and osteonecrosis, developmental abnormalities and secondary malignancies. The association between the various toxicities and therapies is provided in Table 5.

The prominent effects of cancer treatment on the oral mucosa are seen in the early period following treatment and results in oral mucositis. Once mucositis has developed, the oral mucosa is more susceptible to the toxic effects of a second cycle of RT or CT (Sonis 2007). This clinical observation is supported by histomorphological evaluations of oral mucosal specimens taken from patients 6 to 12 months after RT. A decreased number of blood vessels, different expression patterns of adhesion molecules and subpopulations of integrins and macrophages are found (Prott et al. 2002). Patients complaining of a burning sensation months after their acute mucositis has apparently healed support this observation.

Targeted therapy was associated with various oral complications. Recently drugs belong to the Mammalian Target of rapamycin (mTOR) inhibitors were associated with aphthous-like oral lesions, mostly sirolimus, everolimus and temsirolimus. Other oral symptoms, such as dysphagia, dry mouth and dysguesia were reported in relation to mTOR inhibitors as well. Furthermore, additional groups of targeted therapies, such as monoclonal antibodies (cetuximab, bevacizumab) and tyrosine kinase inhibitors (sunitinib, sorafenib, and imatinib) were suggested to have oral adverse events.

Patients post allogeneic HSCT may develop oral mucosal GVHD. GVHD is an allo-immune inflammatory process, which results from a donor-origin cellular response against host tissues. The chronic form of GVHD (cGVHD) occurs in 30–50 % of allogneic transplants and oral involvement is seen in up to 80 % of them (Schubert and Correa 2008). The clinical presentation includes lichenoiod, erythematous, or ulcerative lesions which may be occasionally asymptomatic, but more often is associated with pain, burning sensations, or a rough texture of the oral surfaces. Painful mucosal lesions may represent a significant impediment to nutritional intake and performing oral hygiene.

Clinical examination of the oral tissues can support the diagnosis of GVHD. Correlation of oral changes with systemic manifestations should be considered, although the oral cavity may be the only site affected. Histopathologic evaluation may be complementary to clinical evaluation (Bradley et al. 2003). Scoring of oral cGVHD was addressed by the NIH in 2006 (Pavletic et al. 2006) (Table 6). Other scales may be used for research (Piboonniyom et al. 2005; Elad et al. 2003).

Importantly, GVHD is one of the potential risk factors associated with the development of secondary solid cancers including those presenting in the head and neck area (see “Secondary Malignancy”).

When the oral and pharyngeal mucosa is exposed to radiation, taste receptors are damaged and taste discrimination becomes increasingly compromised (National Cancer Institute 2008; Ruo Redda and Allis 2006; Gamper et al. 2012; Epstein et al. 2010). Loss of saliva flow (hyposalivation) impairs the transport and solubilization of gustatory stimulants to the taste buds, which leads to taste disorders. The outcome may be a reduction in taste sensitivity (hypogeusia), absence of taste sensation (ageusia), or a distortion of normal taste (dysgeusia). Studies in RT patients showed mixed results about the pattern of taste impairment. Some studies showed that sensitivity to sweet mainly decreases and that sensitivity to bitter increases. Others showed that sensitivity to bitter and salty simulants is mainly decreased (Ruo Redda and Allis 2006) and that umami was the only taste to be impaired (Shi et al. 2004).

After 3–4 weeks of radiation it is common for patients to complain of an absence of a sense of taste. It will generally take upwards of several months after the end of radiation therapy for taste receptors to recover and become functional, but it may require up to 2 years (Ruo Redda and Allis 2006).

Radioactive iodine in the form of (Paulino et al. 2000) I¹³¹ is used to treat thyroid cancer and reportedly causes taste alterations in approximately 10 % of patients (Rosenbluth et al. 2005, Lee JN et al. 2010).

Most commonly used cytotoxic agents have been linked to chemosensory disorders (Comeau et al. 2001; Bernhardson et al. 2007; Berteretche et al. 2004), and are known to damage chemosensory structures and disrupt saliva and mucus production, which indirectly affects the sense of taste (Schiffman and Zervakis 2002). Research into the side effects of cytotoxic chemotherapies indicates that 46–77 % of patients receiving chemotherapy report changes in taste (Lindley et al. 1999; Foltz et al. 1996; Rhodes et al. 1994; Wickham et al. 1999; Youngblood et al. 1994). However, most of these changes resolve within a few months after chemotherapy ends with little long-term impact (Bernhardson et al. 2007).

Approximately 20 % of patients 90–100 days post HSCT report moderate to severe levels of taste change (Epstein et al. 2002). More patients report reduced intensity of taste and abnormal tastes. However, it seems that these taste changes have a limited impact on QOL (Epstein et al. 2002). In patients 24–30 months post HSCT taste changes are also noted (Marinone et al. 1991). In patients that received allogeneic transplants, hypogeusia to salt and sour, but no difference in sweet or bitter are reported. In recipients of autologous transplants statistically significant taste changes are seen (Marinone et al. 1991). These finding are ambiguous as other studies show recovery in 80 % of patients 1 year-post HSCT (Mattsson et al. 1992). It is important to note that in pediatric patients undergoing HSCT taste changes may resolve faster (Cohen et al. 2012).

Long-term salivary gland dysfunction is a common complication of cancer treatment, predominantly in RT and in allogeneic HSCT patients. Salivary gland impairment is also well recognized following CT, and generally recovers within 6 months (Chaushu et al. 1995).

The RT-induced damage to the salivary gland results in a quantitative and qualitative change in saliva. Consequently, there is loss of salivary function, reduction in salivary flow and symptoms of dry mouth. The irradiated volume of salivary gland tissue correlates directly with the severity of oral complications (Cheng et al. 1981; Eisbruch et al. 1999; Roesink et al. 2001). The bottom range of the mean doses which have been found to cause significant salivary flow reduction is from 26 to 39 Gy (Roesink et al. 2001; Eisbruch et al. 2001). Changes in quantity of saliva occur shortly after radiotherapy. With cumulative RT dose of 60–70 Gy, more irreversible extensive damage to salivary flow rate is detected (Vissink et al. 2003). The implementation of alternative fractionation schedules, like hyper fractionation and accelerated fractionation has only a negligible positive effect on salivary gland function and morphology in animal models (Vissink et al. 2003; Price et al. 1995; Coppes et al. 2002). However, evidence in humans shows that xerostomia (a sensation of decreased saliva) is worse in accelerated fractionation compared to conventional fractionation (Awwad et al. 2002).

The introduction of IMRT allows more accurate delivery of a specific radiation dose to the tumor and spares the surrounding tissues, including major salivary glands. There is much encouraging data suggesting that salivary gland impairment is reduced by using IMRT compared to traditional radiotherapy techniques (Rathod et al. 2013). A systematic review concluded that the benefits of IMRT on salivary gland function, xerostomia, and xerostomia-related QOL are most pronounced late (≥ 6 months) after radiotherapy and there are improvements in xerostomia-related QOL over time (Jensen et al. 2010).

It is unclear yet what the sparing effect of novel radiation techniques such as cyberknife, protons and carbon ions is (Thariat et al. 2011).

Dry mouth in HSCT patients is a multifactorial condition. The most common etiologies are the conditioning regimen, chronic GVHD (cGVHD) and chronic administration of medication. In addition altered oral intake may be associated with dehydration.

Cancer treatment and cGVHD also result in a change of salivary composition. Clinically, saliva color becomes yellowish to brownish, mucoid, sticky and viscous. The qualitative changes in saliva include increased viscosity, reduced buffering capacity, altered salivary electrolyte concentrations, and increased levels of anti-bacterial proteins including sIgA, lysozyme and lactoferin (Vissink et al. 2003; Makkonen et al. 1986; Valdez et al. 1993; Izutsu et al. 1985; Hiroki et al. 1994; Nagler et al. 1996). When flow rates and buffer capacity is diminished, salivary pH is lowered. In the presence of food containing fermentable carbohydrates, plaque pH is decreased and the lack of clearance, due to decreased salivary flow, inhibits the rise of the plaque pH back to normal levels. The prolonged low pH environment impairs the balance between demineralization and remineralization predisposing to greater demineralization and results in dental caries. In the absence of preventive therapy, primarily fluoride, the dental caries progress very rapidly (see following paragraphs about “Dentition and Periodontium”). In addition, the acidic plaque pH provides optimal conditions for the shift of the oral flora to a cariogenic flora (Brown et al. 1975). Since the decrease in salivary flow rate is greater than the increase in immunoprotein and lysozyme levels, a significant immunoprotein deficit compromises saliva’s protective role (Kielbassa et al. 2006).

Patients complaining about xerostomia often describe that the discomfort increases during night and that adhesion of the tongue to the palate necessitates repeated arousal to drink water during their night sleep. This polydypsia lead to nocturnal polyuria. Clinical evaluation will reveal a dry appearance of the oral mucosa. In extreme oral dryness the oral mucosa may be atrophic, erythematous and fissured. Some patients may describe episodic painful swelling of the salivary glands, which is usually caused by retrograde infection due to the absence of the washing effect of saliva in the salivary ducts. When such an acute sialoadentitis exists, the salivary gland region may be swollen, the covering skin may be erythematous and tender, and salivary expression upon milking will be missing.

The typical manifestation of cGVHD involving the minor salivary glands is multiple mucoceles, with labial and soft-palate mucosa being the most frequently involved sites. Mucoceles often cause a disturbed sensation in the mouth but not pain (Schubert et al. 2004). In rare cases mucoceles may evolve into a large mucocele or ranule.

Hyposalivation has multiple additional consequences (Schubert and Correa 2008; Vissink et al. 2003