Alterations of salivary microbial community associated with oropharyngeal and hypopharyngeal squamous cell carcinoma patients.

The highest number (35.1% of global incident cases) of new oropharyngeal (OP) and hypopharyngeal (HP) cancer cases was reported in South-Central Asia. The highest incidence of HP cancer in India was reported in East Khasi Hills District of Meghalaya, Aizawl District of Mizoram, and Kamrup Urban District of Assam. HP and OP cancer showed the highest mortality rate, worst prognoses and the highest rate of nodal metastases and distant metastases. Thus, research is required to detect specific biomarkers for early prevention and diagnosis for these cancers. Oral microbiome signatures in saliva are considered as a potential diagnostic biomarker for OP and HP cancer. Bacterial profile alterations in OP and HP cancer have not been reported in India population, to establish the association of oral bacteria in the progression of OP and HP cancer; we studied bacterial communities in saliva of eight OP and seven HP cancer patients as compared to healthy controls using 16S rRNA V3-V4 region sequencing. The higher abundance of Haemophilus parainfluenzae, Haemophilus influenzae and Prevotella copri and lower abundance of Rothia mucilaginosa, Aggregatibacter segnis, Veillonella dispar, Prevotella nanceiensis, Rothia aeria, Capnocytophaga ochracea, Neisseria bacilliformis, Prevotella nigrescens and Selenomonas noxia in saliva of OP and HP cancer patients may be considered as a non-invasive diagnostic biomarker for OP and HP cancer patients. Streptococcus anginosus may be considered as a non-invasive diagnostic biomarker for OP cancer patients only. Therefore, evaluation of salivary microbial biomarkers may be informative to understand the pathobiology and carcinogenesis of OP and HP cancer.

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.

Surgical site infections among high-risk patients in clean-contaminated head and neck reconstructive surgery: concordance with preoperative oral flora.

BACKGROUND: Salivary contamination of surgical wounds in clean-contaminated head and neck surgery with free flap reconstruction remains a major cause of infection and leads to significant morbidity. This study investigates the correlation between intraoral flora and surgical site infections (SSIs) among high-risk head and neck cancer patients undergoing resection and free flap reconstruction. METHODS: One hundred twenty-nine patients were identified as being at high risk for infective complications based on cancer stage, tumor size, comorbid factors, and extent of reconstruction. All patients had intraoral swab cultures before surgery. Patients with culture-confirmed SSI after surgery were chosen for analysis, using the κ index and its 95% confidence interval for concordance analysis. All patients received clindamycin and gentamicin for antibiotic prophylaxis for 5 days. Antibiotic susceptibility testing of all isolates was obtained and analyzed. RESULTS: Thirty-seven patients experienced SSI, or an infection rate of 28.3%, occurring at a mean of 9.3 postoperative days. The overall concordance between oral flora and SSI was fair to moderate (κ index of 0.25), but detailed analysis shows a higher concordance for known and opportunistic pathogens, such as Pseudomonas aeruginosa and Enterococcus faecalis, compared to typical oral commensals. Antibiotic susceptibility tests show rapid and significant increases in resistance to clindamycin, indicating a need for a more effective alternative. CONCLUSIONS: Predicting pathogens in SSI using preoperative oral swabs did not demonstrate a good concordance in general for patients undergoing clean-contaminated head and neck surgery, although concordance for certain pathogenic species seem to be higher than for typical intraoral commensals. The rapid development of resistance to clindamycin precludes its use as a prophylactic agent.

Association between Helicobacter pylori infection and laryngo-hypopharyngeal carcinoma: a case-control study and review of the literature.

BACKGROUND: Gastroesophageal reflux, by exposing the pharynx to Helicobacter pylori (H. pylori), is a potential risk factor for laryngo-hypopharyngeal carcinoma. Its possible association has been inconsistent. In this case-control study, we investigated the relationship between H. pylori seropositivity and laryngo-hypopharyngeal carcinoma in Iran. METHODS: We had 105 healthy controls (group A), 70 cases of laryngeal carcinoma (group B), and 28 cases of hypopharyngeal carcinoma group (group C). Age, sex, smoking habit, alcohol use, and H. pylori serology were determined for all subjects. RESULTS: Groups were matched in age and alcohol use. Smoking and H. pylori seropositivity were more common in groups B and C, and male sex was more common in group B (compared with group A). In multivariate regression, the effect of smoking (p <.01, odds ratio [OR] = 2.92) and H. pylori seropositivity (p <.01, OR = 11.49) remained highly significant. CONCLUSION: H. pylori is an independent risk factor for laryngo-hypopharyngeal carcinoma.

Detection of Epstein-Barr virus and human papillomavirus in head and neck tumors.

The presence of Epstein-Barr virus (EBV) DNA and human papillomavirus (HPV) DNA in 74 head and neck tumor tissues was examined by the polymerase chain reaction and DNA sequencing analysis. EBV DNA sequence was detected in all 30 nasopharyngeal-carcinoma tissue samples and in 30 of 44 other head and neck tumor samples. HPV DNA sequence was detected in 14 of 30 nasopharyngeal-carcinoma tissue samples and in 11 of 44 other tumor samples. Coinfection of both viruses was observed in 14 nasopharyngeal-carcinoma tissue samples but only in 5 other head and neck tumor samples including 3 hypopharyngeal-carcinoma tissue samples. Our data indicate that EBV is closely associated with nasopharyngeal- carcinoma and may also be related to hypopharyngeal-carcinoma. In addition, a relatively high percentage of EBV-positive nasopharyngeal- and hypopharyngeal-carcinoma tissue specimens contained HPV sequence. The significance of the coexistence of EBV and HPV in these tumor tissues requires further study.

[Detection of human papillomavirus DNA in hypopharyngeal carcinoma].

The detection of human papillomavirus type-16 and -6b was performed in 28 cases of hypopharyngeal squamous cell carcinomas by polymerase chain reaction. Human papillomavirus (HPV) DNAs extracted from paraffin-embedded metastatic lymph node tissue were used for polymerase chain reaction with amplification of the E1 region of HPV genotype 6b and the E6 region of HPV genotype 16. HPV type 6b sequences were detected in three cases; positive amplification of type 16 sequences was also seen in three cases. These findings suggest that HPV infection might be closely associated with the development of some hypopharyngeal carcinomas as it is with laryngeal and uterine cervical carcinogenesis.

Human papilloma virus and carcinoma of the laryngopharynx.

The presence of human papillomavirus (HPV) genomes 6, 11, 16 and 33 in 16 patients with laryngopharyngeal carcinomas was examined by means of a polymerase chain reaction. HPV genomes were detected in 75 per cent of cases. In hypopharyngeal carcinoma, HPV 6 and 11 were present in adjacent tissue but absent from the tumour. HPV 16 and 33 were present in 40 per cent of laryngeal tumours and adjacent tissue. These results suggest that HPV 16 and 33 may be closely associated with the development of some laryngopharyngeal carcinomas.