Randomised, double-blind, placebo-controlled trial of oral probiotic Streptococcus salivarius M18 on head and neck cancer patients post-radiotherapy: a pilot study.

Xerostomia detrimentally affects the oral health of many head and neck cancer patients who undergo radiotherapy. Its sequelae become an ongoing burden for patients that often manifest as periodontal disease and dental decay. Bacteria play a major role in the pathogenesis of these conditions and here we explore the use of an oral probiotic to beneficially modulate the oral bacterial community post-radiotherapy. In this pilot study, a four-week intervention with oral probiotic lozenges containing Streptococcus salivarius M18 was trialled in seven patients. Post-intervention changes in oral health and in the composition of the plaque and saliva bacterial communities were compared with six patients in a placebo group. An improvement in periodontal screening and plaque index scores was observed in both groups after the intervention period. The oral probiotic lozenges did not significantly impact bacterial community composition or diversity, nor did the probiotic lozenges increase the relative sequence abundance of ZOTU_1 (the probiotic-associated sequence assigned to S. salivarius) detected in the samples. Network analyses suggest negative interactions occurred between ZOTU_1 and species from the periopathogenic genera Campylobacter, Fretibacterium, Selenomonas and Treponema but further investigation is required to more fully understand the beneficial properties of this oral probiotic.

Oral microbial influences on oral mucositis during radiotherapy treatment of head and neck cancer.

PURPOSE: Oral mucositis (OM) remains a significant complication developed by many patients undergoing radiotherapy (RT) to the head and neck region. Emerging data suggest oral microbes may contribute to the onset and severity of this acute side effect. METHODS: In this study, saliva and oral swabs from head and neck cancer patients undergoing RT were collected. We employed molecular microbiological techniques to study the bacterial communities present in saliva, and both the bacterial and fungal communities present on the buccal mucosa and lateral tongue. Changes in microbiota composition with increasing radiation dose and the presence of mucositis were examined. RESULTS: The data suggest that the salivary microbiota remain stable during RT and are consistently dominated by Streptococcus, Prevotella, Fusobacterium and Granulicatella. Obligate and facultative anaerobic Gram-negative bacilli (GNB) Bacteroidales G2, Capnocytophaga, Eikenella, Mycoplasma and Sneathia, as well as anaerobic GNB in the periopathogenic genera Porphyromonas and Tannerella, were all positively correlated with ≥ grade 2 OM. Significant increases in the relative abundances of Bacteroidales G2, Fusobacterium and Sneathia were identified in buccal mucosa swabs at sites of ≥ grade 2 OM (p < 0.05). Furthermore, the abundance of several GNB (Fusobacterium, Haemophilus, Tannerella, Porphyromonas and Eikenella) on the buccal mucosa may influence patient susceptibility to developing OM. Candida was widely detected in buccal mucosa swabs, regardless of mucositis status. CONCLUSIONS: Our findings support previously hypothesized associations between oral health and the pathogenesis of OM, highlighting the importance of oral health interventions for head and neck cancer patients.

Microbial and inflammatory-based salivary biomarkers of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) patients often present with poor oral health, making it difficult to assess the relationship between oral microbes, inflammation, and carcinoma. This study investigates salivary microbes and inflammatory cytokines as biomarkers for HNSCC, with consideration of oral health. Saliva was collected from 30 participants, including 14 HNSCC patients and 16 participants representing both dentally compromised and healthy individuals. Bacterial and fungal communities were analyzed based on 16S rRNA gene and ITS1 amplicon sequencing, respectively, and concentrations of inflammatory cytokines were quantified using a cytometric bead array, with flow cytometry. Diversity-based analyses revealed that the bacterial communities of HNSCC patients were significantly different to those of the healthy control group but not the dentally compromised patients. Fungal communities were dominated by Candida, irrespective of cohort, with Candida albicans comprising ≥96% of fungal sequences in most HNSCC patients. Significantly higher concentrations of interleukin (IL)-1ß and IL-8 were detected in HNSCC and dentally compromised patients, when independently compared with healthy controls. IL-1ß and IL-8 concentrations were significantly positively correlated with the abundance of C. albicans. Our findings suggest that salivary microbial and inflammatory biomarkers of HNSCC are influenced by oral health.

Human papillomavirus and oropharyngeal squamous cell carcinoma: a New Zealand cohort study.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) are clinically, epidemiologically and prognostically distinct from other OPSCCs. The incidence of HPV-related OPSCCs has increased significantly worldwide over the past few decades. However, no studies of OPSCC with direct molecular HPV testing has been conducted in New Zealand. AIMS: To estimate the proportion of OPSCCs attributable to HPV infections in a New Zealand population with a validated HPV testing algorithm. METHODS: HPV-status was determined by p16 immunohistochemistry and polymerase chain reaction (PCR) of both L1 and E6/7 genes on 55 OPSCCs diagnosed in 2010 and 2011 in Central and South Auckland. Baseline and survival analyses were performed according to HPV status. RESULTS: Forty-one (75%) of OPSCC tumours had HPV infections. There was 98% concordance between p16 immunohistochemistry and real-time E6/E7 PCR. After a median follow-up period of 2.6 years, patients with OPSCC of HPV aetiology had more favourable outcomes compared to patients with HPV-negative OPSCC (hazard ratio 0.14, P = 0.02) after adjustment for other variables. CONCLUSION: This study highlights the significant role that HPV plays in the aetiology of OPSCC in New Zealand, and confirms the high rate of accuracy of p16 immunostaining.

Evaluating the Impact of DNA Extraction Method on the Representation of Human Oral Bacterial and Fungal Communities.

The application of high-throughput, next-generation sequencing technologies has greatly improved our understanding of the human oral microbiome. While deciphering this diverse microbial community using such approaches is more accurate than traditional culture-based methods, experimental bias introduced during critical steps such as DNA extraction may compromise the results obtained. Here, we systematically evaluate four commonly used microbial DNA extraction methods (MoBio PowerSoil® DNA Isolation Kit, QIAamp® DNA Mini Kit, Zymo Bacterial/Fungal DNA Mini PrepTM, phenol:chloroform-based DNA isolation) based on the following criteria: DNA quality and yield, and microbial community structure based on Illumina amplicon sequencing of the V3-V4 region of the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) 1 region of fungi. Our results indicate that DNA quality and yield varied significantly with DNA extraction method. Representation of bacterial genera in plaque and saliva samples did not significantly differ across DNA extraction methods and DNA extraction method showed no effect on the recovery of fungal genera from plaque. By contrast, fungal diversity from saliva was affected by DNA extraction method, suggesting that not all protocols are suitable to study the salivary mycobiome.

Observations of benefit finding in head and neck cancer patients.

The management of head and neck cancer (HNC) can lead to potentially severe physical, functional and psychological disturbances. As a result, many HNC patients develop symptoms of depression following diagnosis and treatment. Finding benefit in a disease and its treatment can reduce the symptoms of depression and enhance quality of life (QOL). 92 patients from the Head and Neck Cancer Clinic at Auckland Hospital completed measures of unmet needs and quality of life at diagnosis, and completed measures of benefit finding, coping, fear of recurrence and depression 12-18 months later. Patients reported at least moderate benefit finding in the majority of areas. More benefit finding was predicted by the presence of more advanced disease, Maori/Pacific Island ethnicity, lower baseline QOL, and the use of active coping strategies. These findings support the view that screening for QOL at diagnosis and facilitating the development of coping skills may lead to improved benefit finding and psychological adjustment in people with head and neck cancer. Identification of the factors that facilitate benefit finding may assist management of patients after treatment for HNC.

Treatment of parotid ductal stenosis and concomitant resolution of autonomic symptomatology.

Salivary retention and recurrent sialadenitis as a result of ductal stenosis is an uncommon condition that presents difficult management problems. Ductal dilation with small angioplasty balloons is recognized to be of low morbidity and can eliminate the possible need for surgical intervention. This case report is interesting in that the successful treatment of parotid duct stenosis was accompanied by the resolution of a spectrum of autonomic symptoms that had seriously compromised the patient's quality of life.

Xerostomia and you.

The aims of management of patients with xerostomia include the provision of a definitive aetiology and diagnosis, and a prognosis for the salivary dysfunction. Salivary flow assessment and function testing, other relevant laboratory tests, and even referrals should be performed as necessary. Management of the condition depends on diagnosis and severity, and includes enhancement of salivary flow, oral lubrication, control of soft-tissue infections and discomfort, and prevention of dental caries.