The Effect of Radiation and Chemoradiation Therapy on the Head and Neck Mucosal Microbiome: A Review

Abstract

Radiation (RT) and chemoradiation therapy (CRT) play an essential role in head and neck cancer treatment. However, both cause numerous side effects in the oral cavity, paranasal sinuses, and pharynx, having deleterious consequences on patients’ quality of life. Concomitant with significant advances in radiation oncology, much attention has turned to understanding the role of the microbiome in the pathogenesis of treatment-induced tissue toxicity, to ultimately explore microbiome manipulation as a therapeutic intervention. This review sought to discuss current publications investigating the impact of RT and CRT-induced changes on the head and neck microbiome, using culture-independent molecular methods, and propose opportunities for future directions. Based on 13 studies derived from a MEDLINE, EMBASE, and Web of Science search on November 7, 2021, use of molecular methods has uncovered various phyla and genera in the head and neck microbiome, particularly the oral microbiome, not previously known using culture-based methods. However, limited research has investigated the impact of RT/CRT on subsites other than the oral cavity and none of the studies aimed to examine the relationship between the head and neck microbiome and treatment effectiveness. Findings from this review provide helpful insights on our current understanding of treatment-induced oral mucositis, dental plaque, and caries formation and highlight the need for future research to examine the effect of RT/CRT on the sinonasal and oropharyngeal microbiome. In addition, future research should use larger cohorts, examine the impact of the microbiome on treatment response, and study the effect of manipulating the microbiome to overcome therapy resistance.

Microbial Analysis of Obturators During Maxillofacial Prosthodontic Treatment Over an 8-Year Period

“…In addition to C. albicans, the other microbial species found most commonly by percentage contribution during radiotherapy were F. nucleatum subspecies nucleatum, V. parvula and S. epidermidis. Other studies have reported changes in microbial oral flora in patients with oral carcinomas (Martin and van Saene, 1992;Nagy et al, 1998;Anjali et al, 2020) and during radiation treatment (Llory et al, 1972;Brown et al, 1975;Keene et al, 1981;Keene and Fleming, 1987;Epstein et al, 1991;Abu Shara et al, 1993;Leung et al, 2001;Vissink et al, 2003b;Dahlen et al, 2009;Anjali et al, 2020;Zagury-Orly et al, 2021). These changes have also included an increase in Fusobacterium and Veillonella (Nagy et al, 1998;McIlvanna et al, 2021;Minarovits et al, 2021), as was found in this study.…”

“…Microbial colonisation increased dramatically during radiotherapy and also during the palliative care phase of treatment for patients prior to their death. Significant increases in microbial numbers during radiotherapy have been reported previously (Abu Shara et al, 1993;Vissink et al, 2003b;Belazi et al, 2004;Zagury-Orly et al, 2021). It was also found that all patients undergoing radiotherapy who had C. albicans colonisation exceeding 1x10 5 colonies per swab after 1 week of radiotherapy subsequently required at least antifungal treatment to manage oral complications of head and neck radiotherapy; some required hospitalisation.…”

“…This finding agrees with that found by Clarkson et al (2007) in a Cochrane review, who reported that the percentage of patients developing candidiasis ranged from 5% to 100%, with a median value of 50%. Others have reported the incidence of candidiasis during radiotherapy for head and neck cancer to be from 27 to 77% (Dahiya et al, 2003;Belazi et al, 2004;Jham et al, 2007;Deng et al, 2010;Zagury-Orly et al, 2021).…”

“…In the radiated patient, investigators have found that there is a relative reduction in the amount of low molecular weight salivary proteins such as acidic PRP (Hannig et al, 2006;Lahejj et al, 2015) but the concentration of immunoglobulins and lysozyme are higher after radiation therapy (Laheij et al, 2015). The total daily output of saliva is reduced however, resulting in a significant immunoglobulin deficit, sufficient to create oral flora changes (Brown et al, 1976;Valdez et al, 1993;Almståhl et al, 2001;Almståhl et al, 2008;Zagury-Orly et al, 2021). Numerous studies have documented pronounced population shifts in the oral microflora upon radiation treatment (Llory et al, 1971;Brown et al, 1975;Keene et al, 1981;Keene and Fleming, 1987;Epstein et al, 1991;Leung et al, 2001;Vissink et al, 2003b;Dahlen et al, 2009;Zagury-Orly et al, 2021).…”

“…The total daily output of saliva is reduced however, resulting in a significant immunoglobulin deficit, sufficient to create oral flora changes (Brown et al, 1976;Valdez et al, 1993;Almståhl et al, 2001;Almståhl et al, 2008;Zagury-Orly et al, 2021). Numerous studies have documented pronounced population shifts in the oral microflora upon radiation treatment (Llory et al, 1971;Brown et al, 1975;Keene et al, 1981;Keene and Fleming, 1987;Epstein et al, 1991;Leung et al, 2001;Vissink et al, 2003b;Dahlen et al, 2009;Zagury-Orly et al, 2021). Among aerobic organisms, significant increases occur in the relative number of S.…”