Infective Endocarditis by Capnocytophaga Species-A Narrative Review.

Bacteria belonging to the genus Capnocytophaga are thin, capnophilic, Gram-negative bacilli with tapered ends that include nine species that are isolated from the mouth of humans and animals and, from a phylogenetical perspective, they belong to the family Flavobacteriaceae. Two more species, namely C. endodontalis and C. stomatis have been recovered from a periapical abscess and human and animal infections, respectively. Capnocytophaga spp. can cause serious and potentially life-threatening infections in humans, such as bacteremia and meningitis, most commonly in the context of penetrating trauma as a result of contact with animals, especially after animal bites. Other invasive diseases such as osteomyelitis, septic arthritis, and infective endocarditis (IE) may also occur more rarely. The aim of this study was to review all previously described cases of IE by Capnocytophaga spp. and provide information about the epidemiology, microbiology, antimicrobial susceptibility, clinical characteristics, treatment, and outcomes of this infection. A narrative review based on a search in PubMed, the Cochrane Library, and Scopus was performed. Studies published until 11 September 2023 providing relevant data for IE caused by Capnocytophaga spp. in humans were included. A total of 31 studies containing data from 31 patients were included. A history of dog bites was present in 10 out of 26 patients (38.5%). A prosthetic valve was present in 3 patients (9.7%). The most commonly infected valve was the aortic valve, followed by the tricuspid valve. Fever, embolic phenomena, paravalvular abscess, and sepsis were the most common clinical presentations. Beta-lactams and aminoglycosides were the antimicrobials most commonly used. Surgery was performed in 20 patients (64.5%). Overall mortality reached 16.1%.

Postoperative Capnocytophaga Sputigena Presenting as Diffuse Recalcitrant Intra-abdominal Abscesses.

Capnocytophaga sputigena is rarely implicated as the cause of postsurgical intra-abdominal abscess because it is almost exclusively found in oral flora. Despite its rarity in intra-abdominal infection, there are examples of this atypical presentation, and an awareness of this organism as a potential etiology of surgical infection is relevant for both obstetric and general surgeons. We report a case of a young female who presented just over a week after an uncomplicated C-section with complaint of abdominal discomfort and fevers. Imaging revealed multiple intra-abdominal fluid collections and cultures revealed the presence of C. sputigena. Percutaneous drainage and intravenous antibiotics were unable to provide significant source control, so she underwent surgical exploration with a multi-specialty team of obstetric and acute care surgeons. Although postsurgical pelvic abscesses are rarely due to C. sputigena, this organism has been documented to serve as a source of intra-abdominal infection.

Structure and Composition of Candidate Phyla Radiation in Supragingival Plaque of Caries Patients.

OBJECTIVE: To investigate the composition and abundance of candidate phyla radiation (CPR) in the oral cavity in caries patients and a healthy population. METHODS: The raw macrogenomic sequencing data for a total of 88 subjects were downloaded from the National Centre for Biotechnology Sequence Read Archive (NCBI SRA) public database according to the public data usage specifications. Trimmomatic (Department for Metabolic Networks, Potsdam, Germany) and Bowtie 2 (University of Maryland, College Park, MD, USA) were used to quality control and dehost the host sequences. Species annotation was made using Kraken2 (Johns Hopkins University, Baltimore, MD, USA) and Bracken (Johns Hopkins University) based on the reference database. According to the results of the species annotation, the species-significant differences and species correlation of caries and healthy oral microbiota in species composition and microbiota diversity were analysed to study the distribution and abundance differences of CPR in the oral environment. RESULTS: Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria were the main components. The relative abundance of TM7 (Candidatus Saccharibacteria) and GN02 (Candidatus Gracilibacteria) of CPR is second only to the aforementioned five bacteria, indicating that CPR is an important part of the oral microbiota. TM7 and GN02 were common to both the caries patients and healthy patients and were detected in all samples, suggesting that CPR is the 'core microbiome'. There was a correlation between CPR and a variety of oral microbiota, among which the positive correlation with Capnocytophaga was the strongest, suggesting that Capnocytophaga might be the potential host bacteria of CPR. CONCLUSION: CPR is an indispensable part of the oral microbiota. It is the 'core microflora' of the oral cavity and may play an important role in the stability and function of the oral microecological environment. Capnocytophaga may be the potential host bacteria of CPR.

Treatment of Capnocytophaga sputigena meningitis in a neurosurgical patient.

A woman in her 50s developed meningitis following an endoscopic, endonasal resection of a clival meningioma which was complicated by a cerebrospinal fluid (CSF) leak through the nose. CSF analysis showed a raised white cell count, and Capnocytophaga sputigena was isolated. This organism is an oral commensal and is implicated in periodontal disease; the CSF leak explains the portal of entry. C. sputigena is rarely isolated, and this is the first report of a central nervous system (CNS) infection caused by this organism. A worsening of our patient's dermatological condition, urticaria pigmentosa, coincided with empiric treatment with vancomycin and meropenem, which were therefore discontinued. Treatment was continued with chloramphenicol for 3 weeks, and the patient made a full recovery. Systemic chloramphenicol is uncommonly used in contemporary UK practice, but remains an excellent antibiotic for CNS penetration and it has excellent bioavailability. We anticipate increased chloramphenicol use as the number of multiresistant Gram-negative infection increases.

Putative Novel Species of Genus Capnocytophaga, Capnocytophaga stomatis Bacteremia in a Patient with Multiple Myeloma after Direct Contact with a Cat.

Capnocytophaga species are among the typical zoonotic pathogens causing infections following direct contact with animals. Recently, a putative novel species of zoonotic Capnocytophaga, Capnocytophaga stomatis, was reported. We herein report the first case of bacteremia caused by C. stomatis. A woman in her 80s with multiple myeloma who was receiving bortezomib and dexamethasone therapy was admitted to our hospital with a 2-day history of a fever and right calf redness. She was often licked by her cat. On a blood culture, thin, Gram-negative rods were detected, which were identified as C. stomatis by whole-genome sequencing. The patient was successfully treated with ampicillin-sulbactam treatment. Our case highlights the pathogenic potential of the putative novel Capnocytophaga, C. stomatis, in immunocompromised hosts.

Capnocytophaga zoonotic infections: a 10-year retrospective study (the French CANCAN study).

Zoonotic species of Capnocytophaga genus belong to the oral microbiota of dogs and cats. They may be responsible for serious human infections, mainly after animal bites, with a high mortality rate. In France, only few cases have been reported and no multicenter study has been conducted. Our aim was to describe the French epidemiology of Capnocytophaga zoonosis. We conducted a multicenter (21 centers) retrospective non-interventional, observational study in France describing the epidemiology of Capnocytophaga zoonosis (C. canimorsus, C. cynodegmi, C. canis) over 10 years with regard to clinical and bacteriological data. From 2009 to 2018, 44 cases of Capnocytophaga zoonotic infections were described (C. canimorsus, n = 41; C. cynodegmi, n = 3). We observed an increase (2.5 times) in the number of cases over the study period (from the first to the last 5 years of the study). The most frequent clinical presentations were sepsis (n = 37), skin and soft tissue infections (n = 12), meningitis (n = 8), osteoarticular infections (n = 6), and endocarditis (n = 2). About one-third of patients with sepsis went into septic shock. Mortality rate was 11%. Mortality and meningitis rates were significantly higher for alcoholic patients (p = 0.044 and p = 0.006, respectively). Other comorbidities included smoking, splenectomy, diabetes mellitus, and immunosuppressive therapy are associated to zoonotic Capnocytophaga infection. Eighty-two percent of cases involved contact with dogs, mostly included bites (63%). Despite all isolates were susceptible to the amoxicillin-clavulanic acid combination, three of them were resistant to amoxicillin.

Exposure of Thomsen-Friedenreich Antigen on the Renal Tubules of a Patient with Capnocytophaga Infection-induced Acute Kidney Injury.

Infections with neuraminidase-producing bacteria can lead to acute kidney injury (AKI). We herein report a 74-year-old woman who developed AKI in the course of Capnocytophaga infection, a neuraminidase-producing bacterium. A renal biopsy showed tubulointerstitial injury accompanied by specific binding of fluorescence-conjugated peanut lectin to the tubular epithelial cells, suggesting exposure of Thomsen-Friedenreich antigen (T-antigen) on the tubules. Although AKI is often observed in patients infected with Capnocytophaga, little is known about its etiology and associated pathology. This case suggests that tubulointerstitial injury caused by neuraminidase production and resultant T-antigen exposure is a mechanism of Capnocytophaga infection-induced AKI.

Capnocytophaga periodontitidis sp. nov., isolated from subgingival plaque of periodontitis patient.

Two carbon dioxide-requiring, gliding, Gram-stain-negative strains, designated p1a2T and 051621, were isolated from subgingival plaque in association with severe periodontitis. The 16S rRNA gene sequence analysis revealed that they represented members of the genus Capnocytophaga and had less than 96.4 % pairwise similarity with species with validly published names in this genus. The whole-genome sequences of those strains had less than 91.9 % average nucleotide identity and 48.4 % digital DNA-DNA hybridization values with the other type strains of species of the genus Capnocytophaga, both below the species delineation threshold. The results of pan-genomic analysis indicated that p1a2T and 051621 shared 765 core gene families with the other ten species in this genus, and the numbers of strain-specific gene families were 493 and 455, respectively. The major fatty acids were iso-C15 : 0 and C16 : 0. A combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicate that p1a2T and 051621 should be considered to represent a novel species of the genus Capnocytophaga, for which the name Capnocytophaga periodontitidis sp. nov. is proposed. The type strain is p1a2T (=CGMCC 1.17337T=JCM 34126T).

Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA.

PURPOSE: Oral microbiome plays an important role in oral health and systemic diseases, including cancer. We aimed to prospectively investigate the association of oral microbiome with lung cancer risk. METHODS: We analyzed 156 incident lung cancer cases (73 European Americans and 83 African Americans) and 156 individually matched controls nested within the Southern Community Cohort Study. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Paired t test and the permutational multivariate analysis of variance test were used to evaluate lung cancer risk association with alpha diversity or beta diversity, respectively. Conditional logistic regression models were used to evaluate the association of individual bacterial abundance or prevalence with lung cancer risk. RESULTS: No significant differences were observed for alpha or beta diversity between lung cancer cases and controls. Abundance of families Lachnospiraceae_[XIV], Peptostreptococcaceae_[XI], and Erysipelotrichaceae and species Parvimonas micra was associated with decreased lung cancer risk, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.76 (0.59-0.98), 0.80 (0.66-0.97), 0.81 (0.67-0.99), and 0.83 (0.71-0.98), respectively (all p < 0.05). Prevalence of five pre-defined oral pathogens were not significantly associated with overall lung cancer risk. Prevalence of genus Bacteroidetes_[G-5] and species Alloprevotella sp._oral_taxon_912, Capnocytophaga sputigena, Lactococcus lactis, Peptoniphilaceae_[G-1] sp._oral_taxon_113, Leptotrichia sp._oral_taxon_225, and Fretibacterium fastidiosum was associated with decreased lung cancer risk, with ORs and 95% CIs of 0.55 (0.30-1.00), 0.36 (0.17-0.73), 0.53 (0.31-0.92), 0.43 (0.21-0.88), 0.43 (0.19-0.94), 0.57 (0.34-0.99), and 0.54 (0.31-0.94), respectively (all p < 0.05). Species L. sp._oral_taxon_225 was significantly associated with decreased lung cancer risk in African Americans (OR [95% CIs] 0.28 [0.12-0.66]; p = 0.00012). CONCLUSION: Results from this study suggest that oral microbiota may play a role in the development of lung cancer.

Microbiología de las infecciones causadas por mordeduras de perros y gatos en personas: una revisión / Microbiology of infections caused by dog and cat bites: a review

INTRODUCCIÓN: Las mordeduras causadas por animales de compañía constituyen el 5% de las heridas traumáticas registradas en los servicios de urgencias. OBJETIVO: Conocer los principales agentes infecciosos presentes en las mordeduras provocadas por perros y gatos, tanto de forma individual como conjunta; así como los factores que favorecen la infección. METODOLOGÍA: Se realizó una búsqueda bibliográfica en Pub-Med con la siguiente estrategia de búsqueda: (("Bites, Human"[Mesh]) OR "Bites and Stings"[Mesh]) AND "Infection"[Mesh]. Se incluyeron 24 trabajos en la síntesis cualitativa escritos en lengua inglesa o española, casos clínicos o descriptivos y publicados entre los años 2000 y 2019. RESULTADOS: Las especies más frecuentemente aisladas fueron Capnocytophaga canimorsus en perros y Pasteurella multocida en gatos. La existencia de comorbilidades en el individuo, la mordedura en la mano, o la presencia de signos de alteración del estado general del individuo mordido fueron considerados como factores de riesgo para el desarrollo de la infección tras la mordedura. CONCLUSIONES: Todos los afectados por mordeduras animales deben recibir asistencia médica y considerar la administración de una pauta de profilaxis antimicrobiana con el fin de reducir el riesgo de shock séptico. Por otro lado, es importante advertir al laboratorio de microbiología de la naturaleza de las muestras clínicas obtenidas para alcanzar el mejor diagnóstico etiológico.

BACKGROUND: Bites caused by pets constitute 5% of the traumatic injuries registered in the emergency services. AIM: To know the main infectious agents present in dog and cat bites, both individually and jointly, in humans, as well as the predisposing factors that favor infection and its spread. METHODS: A bibliographic search was carried out in PubMed with the following search strategy: (("Bites, Human" [Mesh]) OR "Bites and Stings" [Mesh]) AND "Infection" [Mesh]. Twenty-four papers were included in the qualitative synthesis written in English or Spanish, clinical or descriptive cases and published between 2000 and 2019. Results: Most frequently isolated species were Capnocytophaga canimorsus in dogs and Pasteurella multocida in cats. The existence of comorbidities in the individual, the bite on the hand, or the presence of signs of alteration of the general state of the bitten individual were considered as risk factors for the development of infection after the bite. CONCLUSIONS: All patients with animal bites should receive medical assistance, and the administration of an antibiotic prophylaxis regimen should be considered to reduce the risk of septic shock. Besides, it is important to advise the microbiology laboratory of the nature of the clinical samples obtained in order to reach the best etiological diagnosis.

Bilateral acute renal cortical necrosis after a dog bite: case report.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats' normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a "reverse rim sign" in contrast-enhanced computed tomography on hospital admission. CASE PRESENTATION: We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. CONCLUSION: We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis - was visible as "reverse rim sign" on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

Screening for prevalence and abundance of Capnocytophaga spp by analyzing NGS data: A scoping review.

BACKGROUND: Capnocytophaga spp. are commensal bacteria of the oral cavity and constitute a genus of the core microbiome. OBJECTIVE: This genus is responsible for many local and systemic conditions in both the immunocompetent and immunocompromised patients, but its beneficial or deleterious role in the microbiota has been little explored. DESIGN: Online databases were used to identify papers published from 1999 to 2019 based on next-generation sequencing (NGS) data to study comparative trials. Work using other identification methods, case reports, reviews, and non-comparative clinical trials was excluded. RESULTS AND CONCLUSION: We selected 42 papers from among 668 publications. They showed a link between the abundance of Capnocytophaga spp. in the oral microbiota and various local pathologies (higher for gingivitis and halitosis; lower in active smokers, etc.) or systemic diseases (higher for cancer and carcinomas, IgA nephropathy, etc.). After discussing the limits inherent to the NGS techniques, we present several technical and biological hypotheses to explain the diversity of results observed between studies, as well as the links between the higher or lower abundance of Capnocytophaga spp and the appearance of local or systemic conditions and diseases.

Subgingival microflora in adolescent females with polycystic ovary syndrome and its association with oral hygiene, gingivitis, and selected metabolic and hormonal parameters.

OBJECTIVES: Research studies suggest that polycystic ovary syndrome (PCOS) may influence the composition of the oral microflora in women. This study aimed to investigate factors affecting the number of selected periopathogens in a young cohort of females with PCOS and to assess the association between oral hygiene, subgingival microbiome, gingival health, and metabolic and hormonal parameters. MATERIALS AND METHODS: Thirty-two subjects with PCOS and twenty-three healthy controls aged 15-19 years were examined periodontally by a calibrated dentist. A real-time PCR method was used for the identification of 9 subgingival microorganisms. Subjects with PCOS underwent blood tests for determination of FSH, LH, total testosterone, DHEA-S, estradiol, SHBG, fasting glucose, fasting insulin, and lipid profile. RESULTS: Gingival index (GI), the proportion of bleeding sites (BOP%), probing depth (PD), and plaque index (PLI) did not differ significantly between cases and healthy age-mates. The control group had significantly higher levels of Peptostreptococcus micros and substantially greater percentage of subjects infected by Treponema denticola. Capnocytophaga gingivalis count was positively correlated with the level of estradiol, while the concentration of HDL-C was negatively correlated with the number of Aggregatibacter actinomycetemcomitans and orange complex bacteria. CONCLUSIONS: PCOS in young patients was not associated with higher pathogenicity of subgingival biofilms. CLINICAL RELEVANCE: Further studies are needed to explain the relationship between hormonal and metabolic abnormalities, subgingival microflora, and periodontal health in patients with PCOS.

Capnocytophaga sputigena bloodstream infection in hematopoietic stem cell transplantations: two cases report and review of the literature.

Capnocytophaga is a group of facultative anaerobic gram-negative bacteria present in the oral cavity of humans, dogs and cats, as part of their normal oral flora. Here, we described two cases of bloodstream infections (BSI) caused by Capnocytophaga in neutropenic autologous hematopoietic stem cell transplantation (auto-HSCT) patients with mucositis (Grade I and Grade III) identified by Maldi-Tof. They were successfully treated with ß-lactam (meropenem and piperacillin-tazobactam). The species C. sputigena was confirmed by 16S rRNA gene sequencing in one patient. The review of literature showed that C. ochraceae was the most frequent species causing BSI in auto-HSCT patients and that the patients usually presented mucositis and were neutropenic at the onset of the infection.

Hemophagocytic syndrome with severe sepsis caused by Capnocytophaga canimorsus.

Capnocytophaga canimorsus, commonly transmitted by dog bites, can cause severe sepsis, and the mortality rate is very high. We experienced a case of hemophagocytic lymphohistiocytosis (HLH) complicated by severe sepsis caused by C. canimorsus. A 58-year-old man with no remarkable medical history was admitted to another hospital with fever and mild consciousness disorder developed 3 days after being bitten by his dog. The next day, the patient developed disseminated intravascular coagulation and shock and was transferred to our emergency medical center. Blood tests showed hyperferritinemia and cytopenia, and bone marrow aspiration was performed. As a result, we diagnosed severe sepsis and HLH. Once antibiotic and steroid therapy was started, the patient's infection and cytopenia improved. Unfortunately, the patient's fingers and toes required amputation, but his life was saved, and he was discharged from hospital. Because HLH may be hidden in such cases, it may be necessary to measure serum ferritin and perform bone marrow aspiration if hyperferritinemia is suspected.

Unexpected pathogen presenting with purulent meningitis.

Herein we report a case of a 67-year-old man with chronic lymphocytic leukaemia who developed acute onset of fever and altered mental status while receiving ibrutinib therapy. He was eventually found to have Capnocytophaga canimorsus meningitis. Timely diagnosis and appropriate antimicrobial therapy was associated with a favourable outcome. We describe challenges associated with appropriate identification of, and briefly review infections caused by Capnocytophaga sp. To our knowledge, this is the first case of invasive C. canimorsus infection in the setting of ibrutinib therapy, and adds to the growing list of serious infections that have been associated with this agent.

CAPNOCYTOPHAGA CANIMORSUS ENDOPHTHALMITIS AFTER CATARACT SURGERY LINKED TO SALIVARY DOG-TO-HUMAN TRANSMISSION.

PURPOSE: To describe a case of acute postoperative bacterial endophthalmitis because of Capnocytophaga canimorsus after cataract surgery, with probable contamination through salivary droplets of dog two days after the procedure. METHODS: An 83-year-old woman who underwent uncomplicated cataract extraction with intraocular lens implantation, presented 12 days later with acute pain, redness, and vision loss in her left eye. Visual acuity was hand motion and clinical findings suggested the diagnosis of acute postoperative endophthalmitis. The patient underwent diagnostic vitrectomy, intravitreal ceftazidime/vancomycin injection and received oral moxifloxacin (400 mg/day). Two days later, she underwent complete pars-plana vitrectomy because of the absence of clinical improvement. Vitreous samples showed gram-negative bacterium on direct examination but cultures remained sterile, which prompted the realization of a broad-range bacterial polymerase chain reaction analysis. RESULTS: Polymerase chain reaction on the vitreous sample detected C. canimorsus, a fastidious gram-negative bacterium of the oral canine flora. When asked for recent contact with dogs, the patient reported having proceeded to an intensive tooth care session for her dog at postoperative Day 2. Intravenous ceftriaxone (2 g/day) was added to the treatment. Anterior and posterior segment inflammation slowly resolved, and final visual acuity was 20/160. CONCLUSION: Although very rare, this complication suggests that patients undergoing ocular surgery should avoid contact with salivary secretions of pets during the early postoperative period. Diagnostic broad-range bacterial polymerase chain reaction is useful to detect unconventional or slow-growing agents in vitreous samples.

Infective endocarditis caused by Capnocytophaga canimorsus; a case report.

BACKGROUND: Capnocytophaga canimorsus is a gram-negative bacterium and an oral commensal in dogs and cats, but occasionally causes serious infections in humans. Septicemia is one of the most fulminant forms, but diagnosis of C. canimorsus infection is often difficult mainly because of its very slow growth. C. canimorsus infective endocarditis (IE) is rare and is poorly understood. Since quite a few strains produce ß-lactamase, antimicrobial susceptibility is pivotal information for adequate treatment. We herein report a case with C. canimorsus IE and the results of drug susceptibility test. CASE PRESENTATION: A 46-year-old man had a dog bite in his left hand 3 months previously. The patient was referred to our hospital for fever (body temperature > 38 °C), visual disturbance, and dyspnea. Echocardiography showed aortic valve regurgitation and vegetation on the leaflets. IE was diagnosed, and we initially administered cefazolin and gentamycin assuming frequently encountered microorganisms and the patient underwent aortic valve replacement. C. canimorsus was detected in the aortic valve lesion and blood cultures. It was also identified by 16S ribosome DNA sequencing. Ceftriaxone were started and continued because disk diffusion test revealed the isolate was negative for ß-lactamase and this case had cerebral symptoms. The patient successfully completed antibiotic treatment following surgery. CONCLUSIONS: We diagnosed C. canimorsus sepsis and IE by extended-period blood cultures and 16S ribosome DNA sequencing by polymerase chain reaction, and successfully identified its drug susceptibility.

Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus.

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC-SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC-SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC-SCC in non smoking HPV negative patients.