Publications by authors named "Monica Pentenero"

50 Publications

Chronic mechanical trauma/irritation and oral carcinoma: A systematic review showing low evidence to support an association.

Oral Dis 2021 Oct 12. Epub 2021 Oct 12.

Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy.

Background: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC).

Objectives: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC.

Data Sources: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science.

Study Eligibility Criteria: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC.

Results: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed.

Conclusions: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.
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http://dx.doi.org/10.1111/odi.14049DOI Listing
October 2021

Oral medicine practice in Europe and Australia: Identifying practitioner characteristics and their clinical activity.

Oral Dis 2021 Apr 19. Epub 2021 Apr 19.

Australian Centre for Oral Oncology Research & Education, Hollywood Private Hospital, Fiona Stanley Hospital, and Australian Clinical Labs, Perth, WA, Australia.

Oral Medicine is a young dental specialty born almost a century ago and deals with orofacial conditions not directly attributable to the most prevalent tooth pathologies such as dental caries or periodontal diseases. Presentations may reflect local disease or orofacial manifestations of more widespread pathology affecting other parts of the body. Due to its recency as a distinct discipline and to heterogeneous global settings, Oral Medicine has not yet achieved a shared scope and definition, as well as a recognized status across the globe. The current report presents survey data gathered from Oral Medicine practitioners in Europe and Australia and aimed to identify practitioner characteristics including demographics, training, clinical and research activity. As expected, Oral Medicine clinical practice commonly deals with conditions such as immune-mediated disorders, potentially malignant disorders, oral mucosal infections and chronic pain disorders, but geographical heterogeneities are observed. The present data, representative of current clinical practice, are valuable in order to understand the evolution of Oral Medicine as a distinct discipline and should be taken into consideration in order to create or update postgraduate training curricula able to meet the needs of future practitioners and the communities they serve.
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http://dx.doi.org/10.1111/odi.13881DOI Listing
April 2021

Antibiotics to prevent complications following tooth extractions.

Cochrane Database Syst Rev 2021 02 24;2:CD003811. Epub 2021 Feb 24.

School of Dentistry, University of Parma, Parma, Italy.

Background: The most frequent indications for tooth extractions, generally performed by general dental practitioners, are dental caries and periodontal infections. Systemic antibiotics may be prescribed to patients undergoing extractions to prevent complications due to infection. This is an update of a review first published in 2012.

Objectives: To determine the effect of systemic antibiotic prophylaxis on the prevention of infectious complications following tooth extractions.

Search Methods: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health Trials Register (to 16 April 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 3), MEDLINE Ovid (1946 to 16 April 2020), Embase Ovid (1980 to 16 April 2020), and LILACS (1982 to 16 April 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.

Selection Criteria: We included randomised, double-blind, placebo-controlled trials of systemic antibiotic prophylaxis in patients undergoing tooth extraction(s) for any indication.

Data Collection And Analysis: At least two review authors independently performed data extraction and 'Risk of bias' assessment for the included studies. We contacted trial authors for further details where these were unclear. For dichotomous outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. For continuous outcomes, we used mean differences (MD) with 95% CI using random-effects models. We examined potential sources of heterogeneity. We assessed the certainty of the body of evidence for key outcomes as high, moderate, low, or very low, using the GRADE approach.

Main Results: We included 23 trials that randomised approximately 3206 participants (2583 analysed) to prophylactic antibiotics or placebo. Although general dentists perform dental extractions because of severe dental caries or periodontal infection, only one of the trials evaluated the role of antibiotic prophylaxis in groups of patients affected by those clinical conditions. We assessed 16 trials as being at high risk of bias, three at low risk, and four as unclear.  Compared to placebo, antibiotics may reduce the risk of postsurgical infectious complications in patients undergoing third molar extractions by approximately 66% (RR 0.34, 95% CI 0.19 to 0.64; 1728 participants; 12 studies; low-certainty evidence), which means that 19 people (95% CI 15 to 34) need to be treated with antibiotics to prevent one infection following extraction of impacted wisdom teeth. Antibiotics may also reduce the risk of dry socket by 34% (RR 0.66, 95% CI 0.45 to 0.97; 1882 participants; 13 studies; low-certainty evidence), which means that 46 people (95% CI 29 to 62) need to take antibiotics to prevent one case of dry socket following extraction of impacted wisdom teeth. The evidence for our other outcomes is uncertain: pain, whether measured dichotomously as presence or absence (RR 0.59, 95% CI 0.31 to 1.12; 675 participants; 3 studies) or continuously using a visual analogue scale (0-to-10-centimetre scale, where 0 is no pain) (MD -0.26, 95% CI -0.59 to 0.07; 422 participants; 4 studies); fever (RR 0.66, 95% CI 0.24 to 1.79; 475 participants; 4 studies); and adverse effects, which were mild and transient (RR 1.46, 95% CI 0.81 to 2.64; 1277 participants; 8 studies) (very low-certainty evidence).  We found no clear evidence that the timing of antibiotic administration (preoperative, postoperative, or both) was important. The included studies enrolled a subset of patients undergoing dental extractions, that is healthy people who had surgical extraction of third molars. Consequently, the results of this review may not be generalisable to all people undergoing tooth extractions.

Authors' Conclusions: The vast majority (21 out of 23) of the trials included in this review included only healthy patients undergoing extraction of impacted third molars, often performed by oral surgeons. None of the studies evaluated tooth extraction in immunocompromised patients. We found low-certainty evidence that prophylactic antibiotics may reduce the risk of infection and dry socket following third molar extraction when compared to placebo, and very low-certainty evidence of no increase in the risk of adverse effects. On average, treating 19 healthy patients with prophylactic antibiotics may stop one person from getting an infection. It is unclear whether the evidence in this review is generalisable to patients with concomitant illnesses or patients at a higher risk of infection. Due to the increasing prevalence of bacteria that are resistant to antibiotic treatment, clinicians should evaluate if and when to prescribe prophylactic antibiotic therapy before a dental extraction for each patient on the basis of the patient's clinical conditions (healthy or affected by systemic pathology) and level of risk from infective complications. Immunocompromised patients, in particular, need an individualised approach in consultation with their treating medical specialist.
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http://dx.doi.org/10.1002/14651858.CD003811.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094158PMC
February 2021

Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO study.

Oral Dis 2021 Jan 29. Epub 2021 Jan 29.

Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.

Objectives: To analyze psychological profiles, pain, and oral symptoms in patients with oral lichen planus (OLP).

Materials And Methods: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes), and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered.

Results: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value < .001 ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D, and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3% of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms.

Conclusions: Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.
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http://dx.doi.org/10.1111/odi.13787DOI Listing
January 2021

Clinical validation of 13-gene DNA methylation analysis in oral brushing samples for detection of oral carcinoma: Italian multicenter study.

Head Neck 2021 05 28;43(5):1563-1573. Epub 2021 Jan 28.

Department of Biomedical and Neuromotor Sciences, Section of Oral Sciences, University of Bologna, Bologna, Italy.

Background: The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples.

Methods: Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value.

Results: DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative.

Conclusion: These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.
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http://dx.doi.org/10.1002/hed.26624DOI Listing
May 2021

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

Support Care Cancer 2020 May 13;28(5):2457-2472. Epub 2020 Feb 13.

University of Rochester Medical Center Oral Medicine, Eastman Institute for Oral Health Rochester, New York, USA.

Objective: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

Methods: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical 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, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible.

Results: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions.

Conclusions: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.
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http://dx.doi.org/10.1007/s00520-019-05256-4DOI Listing
May 2020

Interobserver and intraobserver variability affecting the assessment of loss of autofluorescence of oral mucosal lesions.

Photodiagnosis Photodyn Ther 2019 Dec 30;28:338-342. Epub 2019 Sep 30.

University of Turin, Department of Oncology, Unit of Oral Medicine and Oral Oncology, Italy.

Objectives: The assessment of loss of tissue autofluorescence (LAF) has been proposed as an adjunct to comprehensive oral examination to enhance the detection of mucosal lesions harbouring dysplasia or carcinoma. The assessment of LAF is not based on completely objectified parameters therefore intraobserver and interobserver variability cannot be neglected alongside the issue of correct interpretation of LAF. The present study evaluated intraobserver and interobserver variability in the clinical assessment of LAF as performed by oral medicine practitioners (OMPs) or general dental practitioners (GDPs).

Materials And Methods: Couples of clinical pictures, acquired under white incandescent dental operatory light and during the assessment of LAF performed by VELscope were retrieved. Four OMPs and eight GDPs were asked to assess the pictures and to score the LAF. Kappa statistics allowed the assessment of intra- and inter-observer related variability.

Results: Pictures of 109 lesions representative of all oral mucosal sites and clinical appearances were selected. OMPs had a better intraobserver agreement than GDPs (substantial versus moderate). The moderate (k = 0.506) interobserver agreement observed among both OMPs and GDPs in a 2-score model (positive versus negative), lowered down to poor values only among GDPs when a 3-score or 4-score model (including uncertain judgements) was applied.

Conclusions: A good agreement (k>0.8) was never observed and the present results are similar to previously reported data about conventional oral examination. Irrespective of the diagnostic accuracy, the assessment of AF seems not to be able to improve observer-related variability in the clinical assessment of oral mucosal lesions.
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http://dx.doi.org/10.1016/j.pdpdt.2019.09.007DOI Listing
December 2019

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

Support Care Cancer 2019 Oct 8;27(10):3997-4010. Epub 2019 Jul 8.

Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA.

Purpose: To update the clinical practice guidelines for the use of natural and miscellaneous agents 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 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions.

Conclusions: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.
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http://dx.doi.org/10.1007/s00520-019-04887-xDOI Listing
October 2019

Response to: "Contrasting results of DNA content analysis in oral lichen planus".

Oral Dis 2019 09 26;25(6):1676-1677. Epub 2019 Jun 26.

IRCCS Ospedale Policlinico San Martino, Genova, Italy.

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http://dx.doi.org/10.1111/odi.13133DOI Listing
September 2019

World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review.

Oral Dis 2019 Jun;25 Suppl 1:88-101

Sjogren's Syndrome and Salivary Gland Dysfunction Unit, NIDCR/NIH, Bethesda, MD, USA.

Background: Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.

Objectives: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.

Methods: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.

Results: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.

Conclusions: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.
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http://dx.doi.org/10.1111/odi.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544174PMC
June 2019

World Workshop on Oral Medicine VII: Functional pathways involving differentially expressed lncRNAs in oral squamous cell carcinoma.

Oral Dis 2019 Jun;25 Suppl 1:79-87

Sjogren's Syndrome and Salivary Gland Dysfunction Unit, NIDCR/NIH, Bethesda, MD, USA.

Long non-coding RNAs (lncRNA) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels and are involved in tumorigenesis. They can form complex secondary and tertiary structures and have been shown to act as precursors, enhancers, reservoirs and decoys in the complex endogenous RNA network. They were first reported in relation to oral squamous cell carcinoma (OSCC) in 2013. Here, we summarise the functional roles and pathways of the most commonly studied lncRNAs in OSCC. Existing research demonstrates the involvement of lncRNA within pivotal pathways leading to the development and spread of OSCC, including interactions with key cancer-associated microRNAs such as miR-21. The number of studies on lncRNA and OSCC remains limited in this new field. As evidence grows, the tissue-specific expression patterns of lncRNAs should further advance our understanding of the altered regulatory networks in OSCC and possibly reveal new biomarkers and therapeutic targets.
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http://dx.doi.org/10.1111/odi.13051DOI Listing
June 2019

Variations of salivary concentration of cytokines and chemokines in presence of oral squamous cell carcinoma. A case-crossover longitudinal prospective study.

Cytokine 2019 08 18;120:62-65. Epub 2019 Apr 18.

University of Turin, Department of Oncology, Unit of Oral Medicine and Oral Oncology, Italy.

Salivary biomarkers represent a promising diagnostic tool. Non-invasive and stress-free sampling results in objective parameters able to overcome the need of clinical expertise required for a correct interpretation of early oral squamous cell carcinoma (OSCC). The present study aims at evaluating potential variations in the salivary concentration of cytokines in presence of OSCC. Twenty patients who underwent surgical resection of OSCC were enrolled in order to assess the variation of the salivary concentration of cytokines and chemokines in a longitudinal prospective case-crossover setting. The salivary concentration of 27 salivary cytokines/chemokines was assessed before and after surgical resection of OSCC. In cases of relapsing/recurrent disease further assessments were performed. In presence of OSCC an increased concentration of IL-8(p = 0.004), IL-6(p = 0.005), VEGF(p = 0.014), MIP-1ß(p = 0.033), IP-10(p = 0.047), IL-1β(p = 0.049) was observed; conversely the concentration of IFN-γ(p = 0.036) and IL-5(P = 0.048) decreased. In cases with relapsing/recurrent disease IL-5, IL-6 and MIP-1β showed variations consistent with the previously reported results. Further studies are needed in order to confirm these results and to determine reference values to determine the presence or absence of disease.
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http://dx.doi.org/10.1016/j.cyto.2019.04.009DOI Listing
August 2019

Vascular density and inflammatory infiltrate in primary oral squamous cell carcinoma and after allogeneic hematopoietic stem cell transplantation.

Ann Hematol 2019 Apr 5;98(4):979-986. Epub 2018 Dec 5.

Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, Piazza Giulio Cesare, 11, 70124, Bari, Italy.

Hematopoietic stem cell transplantation (HSCT) recipients have been reported to have an increased risk of chronic graft versus host disease (cGVHD) and hematological and solid cancers. Oral manifestations are the first signs of cGVHD observed in the majority of patients, and oropharyngeal cancer is the most frequent secondary malignancy occurred after HSCT. In this study, we have evaluated the inflammatory infiltrate cell content and correlated with the vascular density in patients affected by primary oral squamous cell carcinoma (OSCC) from previous healthy controls and OSCC after cGVHD. Results have demonstrated that patients with OSCC after GVHD show a more consistent inflammatory infiltrate as compared with the OSCC ones. In detail, the inflammatory background composed of CD3-positive T cells, tryptase-positive mast cells, CD31-positive endothelial cells, and CD68-positive macrophages may be more pronounced in the setting of GVHD + OSCC than in the control group. By contrast, CD20-positive B cells and CD1a-positive dendritic cells were more abundant in the latter population. Finally, a positive correlation was found as between vascular density and inflammatory cell infiltration in both GVHD + OSCC and OSCC groups. Overall, these results confirm the role played by immune cells in enhancing tumor progression and angiogenesis and suggest a potential therapeutic strategy involving inhibition of recruitment of immune cells to the tumor microenvironment and blockade of pro-tumoral effects and pro-angiogenic functions.
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http://dx.doi.org/10.1007/s00277-018-3575-3DOI Listing
April 2019

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications.

Oral Surg Oral Med Oral Pathol Oral Radiol 2018 06 4;125(6):650-669. Epub 2018 Apr 4.

Pathology, Surgical and Hospital Dentistry, University of Louisville, USA.

Identification and management of potentially premalignant oral epithelial lesions (PPOELs) at highest risk of malignant transformation holds great promise for successful secondary prevention of oral squamous cell carcinoma, potentially reducing oral cancer morbidity and mortality. However, to date, neither clinical nor histopathologic validated risk predictors that can reliably predict which PPOELs will definitively progress to malignancy have been identified. In addition, the management of PPOELs remains a major challenge. Arguably, progress in the prevention and treatment of oral premalignancy and cancer will require improved understanding of the underlying molecular mechanisms, facilitating the discovery of diagnostic, prognostic, and predictive markers, as well as the identification of novel targeted therapeutics. This review provides a synopsis of the molecular biomarkers that have been studied in PPOELs and have been correlated with the presence and grade of dysplasia and/or their propensity to undergo malignant transformation to oral squamous cell carcinoma. The emphasis is on highlighting new emerging research fields, particularly epigenetic events, including methylation and micro-RNA regulation. Several promising biomarkers are highlighted. Current limitations and challenges are discussed. Recommendations for future focused research areas, to validate and promote clinically useful applications, are offered.
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http://dx.doi.org/10.1016/j.oooo.2018.03.012DOI Listing
June 2018

DNA aneuploidy relationship with patient age and tobacco smoke in OPMDs/OSCCs.

PLoS One 2017 6;12(9):e0184425. Epub 2017 Sep 6.

Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.

The aim of this study was to investigate the relationship between tobacco smoke habit, patient age, DNA aneuploidy and genomic DNA copy number aberrations (CNAs) in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) patients. DNA aneuploidy was detected by high-resolution DNA flow cytometry (hr DNA-FCM) on DAPI stained nuclei obtained from multiple tissue samples from OPMDs/OSCCs in 220 consecutive patients. Nuclear genomic aberrations were determined in a subset of 65 patients by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. DNA aneuploidy and mean nuclear genomic aberrations were associated with patients' age. In particular, DNA aneuploidy strongly associated with age in non-smoker OPMDs/OSCCs patients. OSCCs from smokers showed a lower prevalence of DNA aneuploidy compared to OSCCs from non-smokers. A higher occurrence of DNA aneuploidy (particularly in smokers' OPMDs) was observed in patients characterized by involvement of a single oral subsite. Our study suggests that: 1) DNA aneuploidy in non-smokers is mainly related to aging; 2) OPMDs/OSCCs involving multiple oral subsites in smokers are less likely to develop DNA aneuploidy compared to non-smokers; 3) OSCC development is characterized by both CIN and CIN-independent mechanisms and that the latter are more relevant in smokers. This study provides evidence that DNA diploid OPMDs may be considered at lower risk of cancerization than DNA aneuploid ones in non-smokers but not in smokers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184425PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587305PMC
October 2017

Usefulness of micro-biopsy in the follow-up of oral lichen planus.

Minerva Stomatol 2016 Oct;65(5):328-31

Department of Dentistry, San Raffaele Hospital and Institute for Scientific Research, Vita-Salute San Raffaele University, Milan, Italy -

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October 2016

Early Arising Sarcoma After Adjuvant Radiotherapy for Oral Squamous Cell Carcinoma.

J Oral Maxillofac Surg 2016 Apr 12;74(4):862.e1-8. Epub 2015 Dec 12.

Associate Professor, Department of Oncology, Unit of Oral Medicine and Oral Oncology, University of Turin, Turin, Italy. Electronic address:

Radiation-induced sarcoma of the head and neck (RISHN) is a rare and long-term complication of radiation therapy (RT). This report describes a case of RISHN characterized by early and insidious onset. An 80-year-old man was surgically treated for advanced oral squamous cell carcinoma of the left retromolar trigone (pT4aN0). Sixteen months after completion of adjuvant RT, an exophytic sessile lesion arose in the left border of the soft palate. Histologic assessment showed a malignant neoplasm with spindle-shaped cells and areas of bone matrix without perivascular or perineural invasion; such features in addition to immunohistochemical assessment (negative for pan-cytokeratin; positive for vimentin; negative for epithelial membrane antigen; negative for p63; Ki-67, 30%) are consistent with poorly differentiated sarcoma (cT1aN0M0). Fifteen months after a wide surgical resection, the patient was free of disease. RISHN is usually an aggressive neoplasm with insidious onset. Nevertheless, early diagnosis followed by complete surgical excision could make the prognosis comparable to that of spontaneous sarcoma.
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http://dx.doi.org/10.1016/j.joms.2015.12.006DOI Listing
April 2016

Genomic DNA Copy Number Aberrations, Histological Diagnosis, Oral Subsite and Aneuploidy in OPMDs/OSCCs.

PLoS One 2015 5;10(11):e0142294. Epub 2015 Nov 5.

Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.

Oral potentially malignant disorders (OPMDs) characterized by the presence of dysplasia and DNA copy number aberrations (CNAs), may reflect chromosomal instability (CIN) and predispose to oral squamous cell carcinoma (OSCC). Early detection of OPMDs with such characteristics may play a crucial role in OSCC prevention. The aim of this study was to explore the relationship between CNAs, histological diagnosis, oral subsite and aneuploidy in OPMDs/OSCCs. Samples from OPMDs and OSCCs were processed by high-resolution DNA flow cytometry (hr DNA-FCM) to determine the relative nuclear DNA content. Additionally, CNAs were obtained for a subset of these samples by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. Our study shows that: i) aneuploidy, global genomic imbalance (measured as the total number of CNAs) and specific focal CNAs occur early in the development of oral cancer and become more frequent at later stages; ii) OPMDs limited to tongue (TNG) mucosa display a higher frequency of aneuploidy compared to OPMDs confined to buccal mucosa (BM) as measured by DNA-FCM; iii) TNG OPMDs/OSCCs show peculiar features of CIN compared to BM OPMDs/OSCCs given the preferential association with total broad and specific focal CNA gains. Follow-up studies are warranted to establish whether the presence of DNA aneuploidy and specific focal or broad CNAs may predict cancer development in non-dysplastic OPMDs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142294PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634987PMC
June 2016

Stage 3 Medication-Related Osteonecrosis of the Posterior Maxilla: Surgical Treatment Using a Pedicled Buccal Fat Pad Flap: Case Reports.

J Oral Maxillofac Surg 2015 Nov 25;73(11):2082-6. Epub 2015 Jun 25.

Associate Professor, Oral Medicine and Oral Oncology Unit, Department of Oncology, University of Turin, Turin, Italy.

Purpose: Stage 3 medication-related osteonecrosis of the jaw (MRONJ) sometimes requires surgical treatment for resolution of the pathology and, in many cases, leads to oroantral communication in the posterior maxilla. The buccal fat pad flap is considered the best surgical choice for closure of large oroantral communications because it provides primary closure and guarantees adequate bone protection with sufficient blood supply for an effective bone healing process.

Materials And Methods: Five consecutive patients affected by stage 3 posterior maxillary MRONJ were treated with surgical removal of the necrotic bone and primary closure of the oroantral communication using a buccal fat pad flap.

Results: In each case, the size of the flap was always sufficient to perfectly close the defect without tension. There were no postoperative complications and the average postoperative hospital stay was 3 ± 1 days. The patients were seen at monthly follow-ups; after 12 ± 4 months of follow-up, no problems were noted in the treated area.

Conclusion: Despite the limited number of cases, the results of this study suggest that, for stage 3 posterior maxilla MRONJ, managing the site with a pedicled buccal fat pad flap and primary closure might guarantee adequate bone protection with sufficient blood supply for an effective bone healing process.
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http://dx.doi.org/10.1016/j.joms.2015.06.165DOI Listing
November 2015

A novel genomic signature reclassifies an oral cancer subtype.

Int J Cancer 2015 Nov 9;137(10):2364-73. Epub 2015 Jun 9.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

Verrucous carcinoma of the oral cavity (OVC) is considered a subtype of classical oral squamous cell carcinoma (OSCC). Diagnosis is problematic, and additional biomarkers are needed to better stratify patients. To investigate their molecular signature, we performed low-coverage copy number (CN) sequencing on 57 OVC and exome and RNA sequencing on a subset of these and compared the data to the same OSCC parameters. CN results showed that OVC lacked any of the classical OSCC patterns such as gain of 3q and loss of 3p and demonstrated considerably fewer genomic rearrangements compared to the OSCC cohort. OVC and OSCC samples could be clearly differentiated. Exome sequencing showed that OVC samples lacked mutations in genes commonly associated with OSCC (TP53, NOTCH1, NOTCH2, CDKN2A and FAT1). RNA sequencing identified genes that were differentially expressed between the groups. In silico functional analysis showed that the mutated and differentially expressed genes in OVC samples were involved in cell adhesion and keratinocyte proliferation, while those in the OSCC cohort were enriched for cell death and apoptosis pathways. This is the largest and most detailed genomic and transcriptomic analysis yet performed on this tumour type, which, as an example of non-metastatic cancer, may shed light on the nature of metastases. These three independent investigations consistently show substantial differences between the cohorts. Taken together, they lead to the conclusion that OVC is not a subtype of OSCC, but should be classified as a distinct entity.
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http://dx.doi.org/10.1002/ijc.29615DOI Listing
November 2015

Peculiar alexithymic traits in burning mouth syndrome: case-control study.

Clin Oral Investig 2015 Nov 14;19(8):1799-805. Epub 2015 Feb 14.

Unit of Oral Medicine and Oral Oncology, Department of Oncology, University of Turin, Regione Gonzole 10, 10043, Orbassano, TO, Italy.

Objectives: The present case-control study aims to assess the occurrence of alexithymic traits in burning mouth syndrome (BMS) subjects and to correlate alexithymic traits to anxious and depressive traits in BMS subjects.

Materials And Methods: Prospectively enrolled BMS and control subjects were administered the 20-item Toronto Alexithymia Scale (TAS-20). Anxiety and depressive traits were assessed using the Hamilton Anxiety Rating Scale and the Montgomery and Asberg Depression Rating Scale. Occurrence of alexithymic traits was compared between BMS and control subjects. Correlation tests were used to measure the importance of alexithymic traits related to demographic characteristics, pain intensity (VAS score), and to the other psychometric scores.

Results: Fifty-eight BMS subjects (46 females and 12 males) had a mean TAS-20 score significantly higher when compared to controls (p < 0.001; r = 0.72), corresponding to an occurrence rate of alexithymic traits of 79.3 versus 6.9%. Alexithymic traits in BMS subjects were just related to depressive traits (p = 0.02; ρ = 0.31).

Conclusions: The high occurrence of alexithymia in BMS is an adjunctive issue in favor of its multifactorial pathogenesis, with a not negligible role for somatization.

Clinical Relevance: Clinicians should be aware of the high occurrence of alexithymic traits among BMS subjects as such traits may affect the doctor-patient relationship.
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http://dx.doi.org/10.1007/s00784-015-1416-5DOI Listing
November 2015

Next-generation sequencing analysis for detecting human papillomavirus in oral verrucous carcinoma.

Oral Surg Oral Med Oral Pathol Oral Radiol 2014 Jul 12;118(1):117-125.e1. Epub 2014 Apr 12.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

Objective: The etiology of oral verrucous carcinoma is unknown, and human papillomavirus 'involvement' remains contentious. The uncertainty can be attributed to varied detection procedures and difficulties in defining 'gold-standard' histologic criteria for diagnosing 'verrucous' lesions. Their paucity also hampers investigation. We aimed to analyze oral verrucous lesions for human papillomavirus (HPV) subtype genomes.

Study Design: We used next-generation sequencing for the detection of papillomavirus sequences, identifying subtypes and computing viral loads. We identified a total of 78 oral verrucous cases (62 carcinomas and 16 hyperplasias). DNA was extracted from all and sequenced at a coverage between 2.5% and 13%.

Results: An HPV-16 sequence was detected in 1 carcinoma and 1 hyperplasia, and an HPV-2 sequence was detected in 1 carcinoma out of the 78 cases, with viral loads of 2.24, 8.16, and 0.33 viral genomes per cell, respectively.

Conclusions: Our results indicate no conclusive human papillomavirus involvement in oral verrucous carcinoma or hyperplasia.
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http://dx.doi.org/10.1016/j.oooo.2014.03.018DOI Listing
July 2014

Differential expression of HER2, STAT3, SOX2, IFI16 and cell cycle markers during HPV-related head and neck carcinogenesis.

New Microbiol 2014 Apr 1;37(2):129-43. Epub 2014 Apr 1.

Department of Oncology, University of Turin at San Luigi Hospital, Turin, Italy.

The aim of this study was to analyze protein and gene expression of HER2 in 224 head and neck precancerous and malignant lesions by immunohistochemistry and FISH analysis. In parallel, expression of pStat3, Sox2, IFI16 and p16, Ki67 was evaluated. Immunohistochemical analysis was assessed on formalin-fixed paraffin-embedded (FFPE) tissue specimens. A combined method for HPV detection consisting of p16 immunostaining and two PCR probes was applied. HER2 gene status was evaluated by FISH analysis. HPV DNA was detected in 24% of cases with predominant HPV16 genotype. HPV-positive lesions had higher HER2, pStat3 and within carcinoma group, and higher IFI16 expression compared to the HPV-negative group (Fig. 1A-B-C). A strong positive correlation between Sox2 and proliferative activity was observed, whereas IFI16 expression displayed a negative relationship with Sox2 and Ki67 activity. The most striking result was higher pStat3 expression in HPV-positive lesions and its strong positive correlation with IFI16 expression. The presence of HPV may induce upregulation of HER2/neu, pStat3 and IFI16. High levels and a strong positive correlation between pStat3 and IFI16 suggest their synergistic pro-apoptotic effects in HPV-positive lesions.
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April 2014

Microbiopsy a novel sampling technique to early detect dysplastic/malignant alterations in oral mucosal lesions: practicability by general dentists.

J Oral Pathol Med 2014 Jul 3;43(6):435-40. Epub 2014 Feb 3.

Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Turin, Italy.

Background: When used in oral medicine clinics, microbiopsy is able to obtain tissue fragments suitable for a highly sensitive first-level diagnosis of dysplastic/malignant alterations in oral mucosal lesions. If feasible by general dentists, this sampling technique could reduce the diagnostic delay for oral malignant and premalignant lesions. This study assesses the adequacy of microbiopsy samples when taken by general dentists.

Methods: Fifty dentists, without specific training on oral medicine, volunteered for enrolment. They were given brief training and asked to prospectively sample any mucosal lesion observed during their routine practice. The sample adequacy features were assessed.

Results: The dentists sampled 152 lesions; there were 92.1% of adequate samples (140/152), and the BMZ was visible in 78.6% of these (110/140). Neither the clinical aspect nor lesion site affected either the adequacy or the presence of BMZ.

Conclusions: The high adequacy rate observed and the advantages histological specimens have over cytological ones go to support the feasibility of microbiopsy taken by general dentists for the characterization of oral mucosal lesions and in selecting those requiring further assessment in specialized oral medicine centres.
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http://dx.doi.org/10.1111/jop.12161DOI Listing
July 2014

Impact of academic and continuing education on oral cancer knowledge, attitude and practice among dentists in north-western Italy.

J Cancer Educ 2014 Mar;29(1):151-7

Department of Oncology, Oral Medicine and Oral Oncology Unit, University of Turin, Regione Gonzole 10, 10043, Orbassano, TO, Italy,

The present study aims to assess the knowledge, attitude and practice of dentists practicing in the Turin Province (north-western Italy) regarding oral cancer prevention and early detection, to weigh the impact of academic and continuing education and to compare actual and perceived knowledge/practice. A survey was prospectively carried out using an anonymous 23-item questionnaire. Bivariate analyses, multivariate logistic regression analyses and Spearman's correlation analyses examined the overall effect of demographic/background characteristics of responders, with particular emphasis on academic and continuing education. The responder group was formed by 450 dentists representative of the Turin Province Council of Dentists. Both academic and continuing education have a significant impact on knowledge, with a significant association between the time elapsed from continuing education and the degree of knowledge. Knowledge acquired during graduation is seen to significantly weaken in the absence of continuing education. The present study highlights the need of both thorough academic curricula and compulsory current continuing education.
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http://dx.doi.org/10.1007/s13187-013-0562-1DOI Listing
March 2014

Choristoma involving the floor of the mouth and the anterior tongue: a case of teratoid cyst with gastric and respiratory epithelia.

J Oral Maxillofac Surg 2013 Oct 19;71(10):1706-11. Epub 2013 Jul 19.

Academic Researcher, Department of Oncology, Unit of Oral Medicine and Oral Oncology, University of Turin, Turin, Italy. Electronic address:

Oral dysontogenic cysts result from defective embryonic development. Among them teratoid cysts are the most unusual presentation and may be lined by gastric, intestinal, respiratory, squamous, ciliated epithelium or even pancreatic structures. Teratoid cysts containing respiratory and gastrointestinal epithelium have typically been called choristomas. This article describes a 15-year-old boy presenting a choristoma involving both the floor of the mouth and the anterior tongue and characterized by the presence of squamous epithelium with skin adnexa, gastric and respiratory epithelium.
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http://dx.doi.org/10.1016/j.joms.2013.04.020DOI Listing
October 2013

Chromosomal instability, DNA index, dysplasia, and subsite in oral premalignancy as intermediate endpoints of risk of cancer.

Cancer Epidemiol Biomarkers Prev 2013 Jun 29;22(6):1133-41. Epub 2013 Apr 29.

IRCCS AOU San Martino - IST, Genova, Italy.

Background: Chromosomal instability and aneuploidy may represent biomarkers of oral exposure to damaging agents and early signs of clinical disease according to the theory of "oral field cancerization."

Methods: The hypothesis was tested that the DNA index (DI) values, obtained by high-resolution DNA flow cytometry (DNA-FCM), may potentially contribute to oral cancer risk prediction. For this purpose, the DI of oral fields of normal-appearing mucosa and oral potentially malignant disorders (OPMDs) in 165 consecutive patients was tested for association with dysplasia and/or the oral subsites of tongue and floor of the mouth taken as high-risk intermediate endpoints surrogate of cancer clinical endpoints. The association was evaluated by logistic regression using patient gender, age, tobacco, cigarette smoking habit, and alcohol abuse as confounding variables.

Results: Different DI models provided evidence of statistical significant associations. Subdividing the DI values in diploid, near-diploid aneuploid, and high or multiple aneuploid from both OPMDs and oral normal-appearing mucosa, ORs, respectively, of 1, 4.3 (P = 0.001), and 18.4 (P < 0.0005) were obtained.

Conclusion: Routine DI analysis by high-resolution DNA-FCM seems potentially useful to complement dysplasia and subsite analysis for assessment of oral cancer risk prediction and for a better management of the patients with OPMDs. Work is in progress to validate the present findings in a prospective study with clinical endpoints.

Impact: Identifying DNA abnormalities in oral premalignancy may lead to biomarkers of oral exposure and cancer risk and potentially to more effective prevention measures.
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http://dx.doi.org/10.1158/1055-9965.EPI-13-0147DOI Listing
June 2013

Chromosomal instability, aneuploidy and routine high-resolution DNA content analysis in oral cancer risk evaluation.

Future Oncol 2012 Oct;8(10):1257-71

Department of Diagnostic Oncology, Biophysics & Cytometry Section, IRCCS A.O.U. San Martino-IST, Largo Rosanna Benzi n.10, 16132, Genoa, Italy.

Carcinogen exposure of the oral cavity is thought to create an extensive 'field cancerization'. According to this model, a very early precursor of oral cancer is a patch of normal-appearing mucosa in which stem cells share genetic/genomic aberrations. These precancerous fields then become clinically visible as white and red lesions (leuko- and erythro-plakias), which represent the vast majority of the oral potentially malignant disorders. This review focuses on aneuploidy (where it is from) and on biomarkers associated with DNA aneuploidy in oral mucosa and oral potentially malignant disorders, as detected by DNA image and flow cytometry. Data from the literature strongly support the association of DNA ploidy with dysplasia. However, work is still needed to prove the clinical value of DNA ploidy in large-scale prospective studies. Using high-resolution DNA flow cytometry with fresh/frozen material and the degree of DNA aneuploidy (DNA Index) might improve the prediction of risk of oral cancer development.
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http://dx.doi.org/10.2217/fon.12.116DOI Listing
October 2012

Clinical and histological features of gingival lesions: a 17-year retrospective analysis in a northern Italian population.

Med Oral Patol Oral Cir Bucal 2012 Jul 1;17(4):e555-61. Epub 2012 Jul 1.

Department of Biomedical Sciences and Human Oncology, Oral Medicine Section, Lingotto Dental School, University of Turin, Turin, Italy.

Objectives: Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here.

Study Design: The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined.

Results: We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non-calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis.

Conclusions: The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases.
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http://dx.doi.org/10.4317/medoral.17809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3476015PMC
July 2012
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