Preliminary insights into the impact of primary radiochemotherapy on the salivary microbiome in head and neck squamous cell carcinoma

Abstract

Squamous cell carcinoma is the most common type of throat cancer. Treatment options comprise surgery, radiotherapy, and/or chemo(immuno)therapy. The salivary microbiome is shaped by the disease, and likely by the treatment, resulting in side effects caused by chemoradiation that severely impair patients’ well-being. High-throughput amplicon sequencing of the 16S rRNA gene provides an opportunity to investigate changes in the salivary microbiome in health and disease. In this preliminary study, we investigated alterations in the bacterial, fungal, and archaeal components of the salivary microbiome between healthy subjects and patients with head and neck squamous cell carcinoma before and close to the end point of chemoradiation (“after”). We enrolled 31 patients and 11 healthy controls, with 11 patients providing samples both before and after chemoradiation. Analysis revealed an effect on the bacterial and fungal microbiome, with a partial antagonistic reaction but no effects on the archaeal microbial community. Specifically, we observed an individual increase in Candida signatures following chemoradiation, whereas the overall diversity of the microbial and fungal signatures decreased significantly after therapy. Thus, our study indicates that the patient microbiome reacts individually to chemoradiation but has potential for future optimization of disease diagnostics and personalized treatments.

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

“…Until the last decade, microbial research in irradiated HNC patients was entirely culture-based ( 3 , 37 ). Cultivation-based analyses greatly limit the identification of microbial species, thus providing significantly less information on biodiversity and polymicrobial environments and no data on the function of the microbiome ( 38 ).…”

“…An increased number and diversity of fungi, in addition to Candida , have been detected (e.g., Peniophora, Stereum, Cladosporium ) ( 3 ). The total number of bacteria tends to decrease immediately after treatment and gradually return, while the relative abundance of certain species (e.g., Streptococcus mutans ) and genera (e.g., Bifidobacterium, Lactobacillus) tend to increase and reflect gut-associated obligate anaerobes ( 3 , 27 , 28 , 33 , 35 ). Regarding archea, there seems to be little to no change due to RT ( 3 ).…”

“…Radiation therapy (RT) is an essential component of HNC treatment. RT alone or combined with chemotherapy [i.e., chemoradiation therapy (CRT)] can be offered as primary treatment, as an adjuvant following surgery, or as palliation for unresectable HNCs ( 3 ). The desired tumoricidal effect of RT inadvertently injures normal cells adjacent to the area targeted ( 4 ).…”

“…The desired tumoricidal effect of RT inadvertently injures normal cells adjacent to the area targeted ( 4 ). This results in several side effects, including oral mucositis (OM), xerostomia, dysphagia, odynophagia, and RT-induced chronic rhinosinusitis (CRS), having a significant impact on the quality of life of patients with HNC ( 3 , 5 , 6 ).…”

Ferroptosis-Related Long Non-Coding RNA signature predicts the prognosis of Head and neck squamous cell carcinoma

“…Although several treatment options such as surgery, radiotherapy and chemotherapy are available, the asymptomatic nature and lack of early detection of HNSCC result in less than 50% 5-year survival rate of individuals with the cancers. In addition, due to the same reasons, even after treatment, the risk of recurrence and metastasis of HNSCC remain high 5 , 6 . Efficient clinical management of HNSCC has been constrained by suboptimal preclinical models or lack of accurate biomarkers for early diagnosis of the cancers.…”