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Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described "clustering of oral symptoms theory," the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account. [ABSTRACT FROM AUTHOR]