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This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of oral high-risk human papillomavirus (hr-HPV) infection and the proportion of hr-HPV–related oropharyngeal squamous cell carcinoma (OPSCC) among Indigenous and non-Indigenous populations. Data Source: Electronic database searches of PubMed, PubMed Central, Embase, MEDLINE, Scope, and Google Scholar were conducted for articles published from January 2000 until November 2019. Review Methods: Studies were included with a minimum of 100 cases assessing hr-HPV infection in either population samples or oropharyngeal cancer tumor series. The objective was to conduct meta-analyses to calculate the pooled prevalence of oral hr-HPV infection by adjusting for age group or sex in primary studies, the incidence of OPSCC, and the proportion of hr-HPV–related OPSCC in Indigenous people and non-Indigenous/general populations. Results: We identified 47 eligible studies from 157 articles for meta-analyses. The pooled prevalence of oral hr-HPV infection was 7.494% (95% CI, 5.699%-9.289%) in a general population, with a higher prevalence among men (10.651%) than women (5.176%). The pooled incidence rate was 13.395 (95% CI, 9.315-17.475) and 7.206 (95% CI, 4.961-9.450) per 100,000 person-years in Indigenous and non-Indigenous populations, respectively. The overall pooled proportion of hr-HPV–related OPSCC was 50.812% (95 CI, 41.656%-59.969%). The highest proportion was in North America (60.221%), while the lowest proportion was in the Asia-Pacific (34.246%). Conclusion: Our findings suggest that in the general population, the prevalence of oral hr-HPV infection is lower among females and those in younger age groups. The incidence of OPSCC was higher among Indigenous than non-Indigenous populations, with the proportion being highest in North America. [ABSTRACT FROM AUTHOR]

Abstract Background Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Background: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis.Methods: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.Results: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions.Conclusions: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible.Results: A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged.Conclusions: Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings. [ABSTRACT FROM AUTHOR]

Background: Dentigerous cysts are usually of developmental nature but may be of inflammatory origin especially in paediatric populations. It is important to understand the histological features of dentigerous cysts to enable accurate diagnosis. The aim of this study is to present epidemiological, clinical features and histopathological features of dentigerous cysts seen in a paediatric tertiary referral hospital.Method: The medical, radiographic and histopathology records of the Department of Pathology, Women's and Children's Hospital, Adelaide, Australia, during January 1998 to December 2013 were reviewed for patients with dentigerous cysts. All cases were re-examined by a specialist oral pathologist, consultant paediatric pathologist and paediatric dentistry registrar.Results: Forty-one cases of dentigerous cysts were found. Patients in the permanent dentition were most frequently affected. Male predilection was observed (male:female 2.42:1). The posterior mandible was the most frequently affected region (63.42%) although maxillary canines were the teeth most commonly associated with dentigerous cysts (29.27%). The majority of cases were incidental findings. Squamous epithelium showing pseudoepitheliomatous hyperplasia (46%) was frequently observed and was significantly present with thicker epithelium (P < 0.0001) and an acute and chronic inflammatory infiltrate (P < 0.001). Inflammatory infiltrate was seen in 75.6% of cases.Conclusions: The current study provides increased knowledge of the histological features of dentigerous cysts in a large retrospective series of paediatric patients and provides further evidence regarding the frequency of inflammatory dentigerous cysts. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy-induced gut toxicity (RIGT) is a debilitating effect of radiotherapy for cancer, often resulting in significant diarrhea and pain. Previous studies have highlighted roles of the intestinal microvasculature and matrix metalloproteinases (MMPs) in the development of RIGT. We hypothesized vascular mediators would be significantly altered in a dark agouti (DA) rat model of RIGT. Additionally, we aimed to assess the effect of MMP-2 and -9 inhibition on the response of tumor-associated microvascular endothelial cells (TAMECs) to radiation. Methods: DA rats were administered 2.5 Gy abdominal irradiation (3 times/week over 6 weeks). Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), von Willebrand factor (VWF), angiostatin, and endostatin expression was assessed at 3, 6, and 15 weeks. Additionally, DA rat mammary adenocarcinoma tumor-associated microvascular endothelial cells (TAMECs) were used to assess the effects of radiation (12 Gy) and the MMP inhibitor SB-3CT on MMP, VEGF, and TGFβ expression, and cell viability. Results: VEGF mRNA expression was significantly increased in the colon at week 15 (p = .0012), and TGFβ mRNA expression was significantly increased in both the jejunum and colon at week 3 (p = .0280 and p = .0310, respectively). Endostatin immunostaining was significantly increased at week 3 (p = .0046), and angiostatin at 3 and 6 weeks (p = .0022 and p = .0135, respectively). MMP-2 and -9 mRNA and total protein levels were significantly increased following irradiation of TAMECs. Although this increase was significantly attenuated by SB-3CT, it did not significantly alter endothelial cell viability or VEGF and TGFβ mRNA expression. Conclusions: Findings of this study support the involvement of VEGF, TGFβ, angiostatin, endostatin, and MMP-2 in the pathobiology of RIGT. However, the relationship between these mediators is complex and needs further investigation to improve understanding of their therapeutic potential in RIGT. [ABSTRACT FROM AUTHOR]

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. [ABSTRACT FROM AUTHOR]

Objective: A study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing oral cancer in an Indian population. Methods: Life-course data collected from a multicentre case-control study in India were used. Interview was conducted to collect information on predictors limited to the time before the onset of symptoms or cancer diagnosis. Predictors included statistically significant risk factors in the multivariable model. A risk score for each predictor was derived from respective odds ratios (OR). Discrimination of the final model, risk scores and various risk score cut-offs was examined using the c statistic. The optimal cut-off was determined as the one with good area under curve (AUC) and high sensitivity. Predictive ability of the regression model and cut-off risk score was determined by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Models were validated from a bootstrap sample. Results: Smoking, chewing quid and/ or tobacco, alcohol, a family history of upper aero-digestive tract cancer, diet and oral hygiene behaviour were the predictors. Risk scores ranged from 0 to 28. Area under the receiver operating characteristic (ROC) curve for risk scores was good (0.866). The sensitivity (0.928) and negative predictive value (0.927) were high, while specificity (0.603) and positive predictive value (0.607) were low for a risk score cut-off of 6. Conclusion: A risk score model to screen for individuals with high risk of oral cancer with satisfactory predictive ability was developed in the Indian population. Validation of the model in other populations is necessary before it can be recommended to identify subgroups of the population to be directed towards more extensive clinical evaluation. [ABSTRACT FROM AUTHOR]

Regimen-related toxicities remain a priority concern within the field of supportive care in cancer. Despite this, many forms of toxicity are under reported and consequently poorly characterised. Although there have been significant improvements in our understanding of regimen-related toxicities, symptom management continues to occur independently raising concerns such as drug interactions and the tendency to emphasise management of a single symptom at the expense of others. This review focuses on two important toxicities induced by chemotherapy; neuropathy/pain and gastrointestinal toxicity, introducing the Toll-like receptor (TLR) 4 pathway as a common component of their pathobiology. Given the global observation of toxicity clusters, identification of a common initiating factor provides an excellent opportunity to simultaneously target multiple side effects of anticancer treatment. Furthermore, identification of common biological underpinnings could perhaps reduce polypharmacy and have pharmacoeconomic benefits. [ABSTRACT FROM AUTHOR]

Background. Oral adverse events (OAEs) associated with multi-targeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions. Methods. We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand-foot skin reaction (HFSR) and rash. Results. The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified. Conclusions. OAEs caused by TKIs and mTORIs may represent dose-limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patient's health-related quality of life. [ABSTRACT FROM AUTHOR]

Background/Aims: Mucositis is the term used to describe damage caused by chemotherapy to mucous membranes of the alimentary tract. RT-PCR has recently been utilised to determine the molecular events that occur in mucositis. As this method relies on the use of a validated endogenous control, this study aims to validate commonly used housekeeping genes in an irinotecan-induced mucositis model. Methods: Rats were administered irinotecan and sacrificed at different time points, in particular 1, 24, 72 and 144 h following treatment. Histopathological damage was assessed by haematoxylin and eosin staining. RT-PCR was used to evaluate the expression of 11 housekeeping genes. Expression stability was determined by the Normfinder program. Matrix metalloproteinase 2 was used as a target gene to validate the appropriateness of the top-ranking housekeeping gene. Results: For normalisation to multiple housekeeping genes, the most stable combination across all time points in the jejunum was Ywhaz/UBC and in the colon UBC/β-actin. SDHA and GAPDH were the most variable genes in the jejunum and colon where they were 4.4 and 3.2 fold upregulated following irinotecan, respectively. Conclusions: For normalisation of irinotecan-induced mucositis gene expression studies, a combination of Ywhaz/UBC and UBC/β-actin should be used in the jejunum and colon, respectively. UBC is the most favourable if restricted to a single housekeeping gene across all time points. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article reviews research on the connection between oral and gastrointestinal health and their implications in clinical management. It explains the link between oral disease and gastrointestinal reflux disease (GORD) with regards to dental erosion, inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, mucositis and the Gardner syndrome and Peutz-Jegher syndrome. It is conclued that the association of changes in the oral cavity and systemic diseases would require an appropriate multidisciplinary management.

Background: Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Proinflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods: Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results: Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions: Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting. [ABSTRACT FROM AUTHOR]

Summary: Toxicities associated with head and neck cancer treatment are common events. Despite the fact that many side effects of cancer treatment are now well controlled, some, such as mucositis and salivary gland hypofunction, continue to be almost inevitable outcomes of cancer treatment. Furthermore, improvements in cancer treatment itself as well as new modalities, such as targeted treatments, may be associated with different toxicities. In this review, common toxicities associated with head and neck cancer treatment will be discussed including those reported to occur with targeted therapies. This review also considers the concept of toxicity clusters, risk factors for toxicity (for example genetics) and individualisation of cancer treatment. [Copyright &y& Elsevier]

Gastrointestinal mucositis involves many changes at the gene level, affecting epithelial/subepithelial interactions and leading to overt damage. The regional specificity and time course of these changes, and how they relate to subsequent mucositis development however remain unknown. The aim of this study was to determine the early time course of gene expression changes along the gastrointestinal tract of the DA rat following chemotherapy. Female DA rats were treated with a single dose of 200 mg/kg irinotecan to induce mucositis, and were killed at short intervals following treatment. Small sections of stomach, jejunum and colon were harvested for analysis of genetic profiles. RNA was hybridised to high density Affymetrix oligonucleotide microarrays. Data analysis was carried out with software package, TimeCourse, freely available through Bioconductor. As early as 1 hr following chemotherapy, expression of hundreds of genes was altered, including those for transcription factors, stress response proteins and protein turnover. These genes are involved in cell proliferation, differentiation and apoptosis along with other cellular processes. At early time points, there was a significant response involving the mitogen-activated protein kinase pathway, cell cycle regulation and cytokine receptor signalling. At later time points, changes to the complement cascade became prominent. We have shown that changes in gene expression following chemotherapy occur by 1 hr, and persist for at least 72 hr after treatment. Many of these changes are highly likely to be specifically related to the subsequent development of gastrointestinal mucositis. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]