Abstract
Radiotherapy-related caries (RRC) is an aggressive and debilitating oral toxicity that affects about half of the patients who undergo radiotherapy (RT) for head and neck cancer (HNC). However, the aetiology of RRC is not fully established, and there are no clinically validated methods for preventing it. To gain a better understanding of the risk factors and the microbiome’s role in causing RRC, we compared clinicopathological characteristics, oncological treatment regimens and toxicities, oral health condition, and oral microbiome at three different oral sites of RT-treated HNC patients with (RRC+) and without RRC (RRC-). We observed no significant differences between these groups in the clinicopathological characteristics and treatment regimens. However, RRC + patients were older and had poorer oral health conditions at the start of the RT treatment, with a lower number of teeth and a higher proportion of rehabilitated teeth compared to RCC- patients. In general, RRC + patients had lower microbiome diversity and the dental biofilm of RRC + patients displayed striking alterations in microbiome composition compared to RRC- patients, including enrichment of acidogenic species (such as Propionibacterium acidifaciens and Lactobacillus fermentum) and altered metabolic potential, with a higher abundance of genes from caries-related species (such as Streptococcus mutants and S. parasanguinis) linked to energy-related pathways associated with the synthesis of amino acids and sugars. We also compared RRC tissue with carious tissue from healthy subjects with conventional caries (CC). RRC tissue showed lower bacterial diversity, a higher prevalence of Lactobacillus dominance (relative abundance ≥ 40%), and different co-occurrence networks compared to CC. We provide oral microbiome insights to better understand RRC aetiology, which point to the potential of microbial-targeted therapies to prevent and treat RRC.