Oral Microbiota and Cancer Development

Oral microbiota are among the most diverse in the human body. More than 700 species have been identified in the mouth, and new sequencing methods are allowing us to discover even more species. The anatomy of the oral cavity is different from that of other body sites. The oral cavity has mucosal surfaces (the tongue, the buccal mucosa, the gingiva, and the palate), hard tissues (the teeth), and exocrine gland tissue (major and minor salivary glands), all of which present unique features for microbiota composition. The connection between oral microbiota and diseases of the human body has been under intensive research in the past years. Furthermore, oral microbiota have been associated with cancer development. Patients suffering from periodontitis, a common advanced gingival disease caused by bacterial dysbiosis, have a 2-5 times higher risk of acquiring any cancer compared to healthy individuals. Some oral taxa, especially Porphyromonas gingivalis and Fusobacterium nucleatum, have been shown to have carcinogenic potential by several different mechanisms. They can inhibit apoptosis, activate cell proliferation, promote cellular invasion, induce chronic inflammation, and directly produce carcinogens. These microbiota changes can already be seen with potentially malignant lesions of the oral cavity. The causal relationship between microbiota and cancer is complex. It is difficult to accurately study the impact of specific bacteria on carcinoma development in humans. This review focuses on the elucidating the interactions between oral cavity bacterial microbiota and cancer. We gather literature on the current knowledge of the bacterial contribution to cancer development and the mechanisms behind it.Peer reviewe

Covid-19 ja suun limakalvomuutokset

Vertaisarvioitu. English summary.Peer reviewe

Gingival cell growth with antiresorptive treatment combined with corticosteroids or antiestrogen

Objectives: Antiresorptive treatment has been shown to impair mucosal cell proliferation, migration, and viability. However, in the clinic, antiresorptives are often used in combination with other drugs. We studied the effect of antiresorptives combined with a corticosteroid or antiestrogen on oral mucosal keratinocytes and fibroblasts. Material and methods: Human gingival keratinocyte and fibroblast cell lines were exposed to bisphosphonates (BPs) and denosumab in different concentrations and durations together with an antiestrogen or corticosteroid. Changes in cell viability, proliferation and migration after exposures were measured. Data were evaluated with hierarchical linear mixed model for repeated measurements. Results: Bisphosphonate exposure suppressed keratinocyte and fibroblast cell viability, proliferation, and migration in a time-dependent manner. Combining a corticosteroid or antiestrogen with BPs further increased this negative effect. Denosumab alone had a mild positive effect on keratinocyte and fibroblast growth. When denosumab was combined with a corticosteroid or antiestrogen, cell growth was suppressed. Conclusions: Our results show that coexisting medications may increase the negative impact of BPs or denosumab on oral mucosal cells.Peer reviewe

Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study

Objective Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methods We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population.Results About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025).Conclusion An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations.Clinical relevance This study provides information that would improve follow-up protocols and treatment guidelines of IBD.Peer reviewe

Human myoma tissue-based extracellular matrix models for testing the effects of irradiation on the HPV positive cells

Background This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro,and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion. Methods HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1-2 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4 Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS (R) Statistics 25). Results All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (p = 0.0001) but not in invasion area (p = 0.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (p = 0.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (p = 0.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (p = 0.008), SiHa (p = 0.0001) and CaSki (p = 0.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (p = 0.013) as the reduction was greater with SiHa than CaSki. Conclusions Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.Peer reviewe

HPV infection and bacterial microbiota in the placenta, uterine cervix and oral mucosa

We investigated the association between HPV infection and bacterial microbiota composition in the placenta, uterine cervix and mouth in thirty-nine women. HPV DNA genotyping of 24 types was conducted using Multimetrix (R). Microbiota composition was characterized by 16S rRNA gene sequencing. HPV DNA was detected in 33% of placenta, 23% cervical and 33% oral samples. HPV16 was the most frequent type in all regions. HPV infection was associated with higher microbiota richness (p = 0.032) in the mouth but did not influence microbial diversity or richness in other samples. HPV infection was associated with higher abundance of Lactobacillaceae (p = 0.0036) and Ureaplasma (LDA score > 4.0, p < 0.05) in the placenta, Haemophilus (p = 0.00058) and Peptostreptococcus (p = 0.0069) genus in the cervix and Selenomonas spp. (p = 0.0032) in the mouth compared to HPV negative samples. These data suggest altered bacterial microbiota composition in HPV positive placenta, cervix and mouth. Whether the changes in bacterial microbiota predispose or result from HPV remains to be determined in future studies

Malignant transformation of oral epithelial dysplasia in Southwest Finland

Oral epithelial dysplasia (OED) is considered a risk for oral squamous cell carcinoma (OSCC). A meta-analysis estimated a mean malignant transformation rate of 12.1% (95% CI 8.1-17.9). The main target of this study was to define how many OED patients develop OSCC in the hospital district of Southwest Finland. A total of 571 patients diagnosed with OED were identified. Their potential subsequent diagnosis of OSCC was derived from the Finnish Cancer Registry. The risk of OSCC development in OED patients was compared with that of the general population without OED. During a mean follow-up of 5.5 (range 0.1-29.0) years 10.9% of OED patients developed OSCC. OED patients had a 44.7-fold higher risk (95% CI 34.4-56.7) of developing OSCC than the general population. The risk was at its highest within two years of OED diagnosis. OED patients in Southwest Finland have a significantly increased risk of developing OSCC relative to the general population, especially within the first two years of dysplasia diagnosis.Peer reviewe

Climacteric symptoms more severe in 2010 than in 2000-experience of Finnish women aged 52-56 years not now or previously on menopausal hormone therapy

Objectives: To analyze and compare the experience of climacteric symptoms and their associations with socio-demographic and health-related characteristics in two cohorts of Finnish women aged 52-56 years, born ten years apart and not now or previously on menopausal hormone therapy (MHT). Study design: Nationwide population-based time-trend study with a large number of participants (n = 1986 + 1988). Main outcome measures: The experience of climacteric symptoms was assessed by 12 commonly used menopause-related symptoms. Results: Women aged 52-56 experienced more moderate or severe symptoms and fewer mild symptoms in 2010 than in 2000. Being unemployed or inactive was associated with more severe symptoms (P = 0.007), but employment status had no effect on the relative odds estimates. Conclusions: The influence of the birth cohort and time-period effects as well as work-related factors on the experience of climacteric symptoms in women not now or previously on MHT needs further research, particularly since the change in the experience of symptoms found in this study occurred within only ten years.Peer reviewe

Psychological behavior patterns and coping with menopausal symptoms among users and non-users of hormone replacement therapy in Finnish cohorts of women aged 52-56 years

Objective: To identify subgroups of women who differ with respect to self-evaluated stress, hostility, optimism and sense of coherence, and to identify differences, if any, in whether these subgroups use or do not use hormone replacement therapy (HT). Study design and methods: This time-trend study is based on the Finnish national HeSSup study, in which nationwide cohorts of Finnish women aged 52-56 years randomly selected in 2000 (n = 1321) and in 2010 (n = 1389) responded to postal questionnaires related to four psychological behavior patterns. Main outcome measures: Relationships between psychological behavior patterns (stress, hostility, optimism and sense of coherence) and how menopausal symptoms are experienced and how this relates to the use of HT. Results: The proportion of HT users was higher among those with more stress and hostility and less optimism and sense of coherence than among those low in stress and hostility and high in optimism and sense of coherence. Conclusions: Differences in psychological behavior patterns influence the perception of menopausal symptoms and the use of HT. When the treatment of women at menopause is planned, psychological behavior patterns should be considered, as these reflect the ability to cope with menopausal symptoms.Peer reviewe