Malignant transformation in oral submucous fibrosis: Tertiary level evidence: An umbrella review.

OBJECTIVES: An umbrella review is a systematic review of systematic reviews, which provides a tertiary level of evidence. This umbrella review of systematic reviews and meta-analysis (SR-MA) aimed to determine the proportion of oral cancer (OC) development in oral submucous fibrosis (OSF) patients. MATERIALS AND METHODS: We searched electronic databases including PubMed, Scopus, Web of Science, Cochrane and grey literature. Two reviewers independently screened abstracts and assessed for eligible papers. The methodological quality of SR-MA was evaluated using AMSTAR2, and we also checked the quality of evidence of the included papers. RESULTS: Out of 454 papers identified in the primary search, 105 underwent eligibility screening. Inclusion criteria were met by four SR-MA. OC ratios ranged between 4.2% and 6% for OSF. Substantial heterogeneity was observed for this outcome in all four MA (I2 = 71.31% to 86.37%). None of the SRs assessed the quality of evidence, and half of them were judged to be of critically low methodological quality. CONCLUSION: There is lack of quality of evidences and critically low methodological quality among SRs and MA leading to substantial heterogeneity. However, due to potentially malignant nature, OSF patients should be monitored carefully for early detection of OC.

Significance of HIF-1α and CD105 in establishing oral squamous cell carcinoma associated with oral submucous fibrosis a distinct clinicopathological entity.

Context: Oral squamous cell carcinoma associated with oral submucous fibrosis (OSCC with OSMF) is clinicopathologically a distinct entity. However, scientific proof in view of assessment of biomarkers of hypoxia and neoangiogenesis to differentiate them are lacking. The expression of hypoxia-inducible factor 1-α (HIF-1α) and CD105 in OSCC with and without OSMF possibly will be explicated along these lines. Aim: This study aims to evaluate the molecular basis of hypoxia and neoangiogenesis in terms of immunohistochemical expression of HIF-1α and CD105 in OSCC with and without OSMF cases. Settings and Design: A retrospective cohort. Subjects and Methods: The study comprise of 203 histopathologically diagnosed surgically operated cases of OSCC retrieved from the departmental archives. The OSCC cases were subgrouped into two, OSCC with OSMF (Group I) and OSCC without OSMF (Group II). The evaluation of hypoxia and angiogenesis was carried out by immunohistochemical markers, HIF-1α and CD105. MVD is the parameter of angiogenesis expressed by CD105. Statistical Analysis Used: Differences in CD105, and HIF-1α immunoreactivity between study groups were done using descriptive statistics using "Kruskal-Wallis test," "Mann-Whitney test." Statistical significance was set at P < 0.05. Results: On comparison of MVD in Group I and II, statistically significant difference was found in MVD (8.88 ± 3.41, 16.13 ± 5.86, P = 0.0001). The HIF1-α expression was less in Group I (6.85 ± 2.62) as compare to Group II (7.22 ± 3.08) but the difference was statistically nonsignificant (P = 0.35). Conclusions: The OSCC with OSMF is not only clinicopathologically distinct entity of OSCC but also diverse in its molecular pathogenesis as explicited by distinct expression of HIF-1 α and CD105.

Prevalence of Trismus and Its Impact on Oral Health-Related Quality of Life in Patients Treated for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma, one of the most common malignancies, has a poor prognosis due to impairment in oral functions secondary to treatment. Trismus one of the major causes of impairment of oral function. The present study investigated the prevalence of trismus and its impact on oral health-related quality of life (OHRQoL) in patients treated for oral squamous cell carcinoma (OSCC). The maximum inter-incisal mouth opening of hundred OSCC patients was recorded at post-treatment and 3 months post-treatment. OHRQoL questionnaire (OHIP-14) was intervened to assess the OHRQoL of patients post-treatment and 3 months follow-up, with emphasis on correlation with grades of trismus. The prevalence of trismus was 16% pre-treatment, 72% post-treatment, and 62% at 3 months after treatment. The overall OHIP-14 scores indicated that patients with trismus reported greater impairment of OHRQoL than those without trismus at the end of treatment and 3 months follow-up. At the end of treatment, patients with severe trismus demonstrated a higher mean OHIP-14 score (23.47 ±3.34) than those with moderate (17.72 ±2.83) and mild trismus (12.66 ±3.84) with statistically significant differences (p <0.001). Equivalent results were obtained at 3 months follow-up period. Patients with trismus suffer greater impairment of OHRQoL. The findings demand the need of identifying risk factors for developing trismus and early institution of newer/modified treatment approaches for better OHRQoL in OSCC survivors.
.

Oral Psychosomatic Disorders in Family Caregivers of Oral Squamous Cell Carcinoma Patients.

OBJECTIVE: To investigate the oral psychosomatic disorders (PSDs) in family caregivers (FCs) of oral cancer (OC) patients and to evaluate the correlation between these oral PSDs to severity of depression anxiety and stress. METHODS: A total of 50 participants were included each in first degree relative (FDR), second degree relative (SDR) and control group. All the participants completed DASS-21 questionnaire and were subjected to thorough clinical history and oral examination. RESULTS: All the FCs reported statistically significant higher mean levels of depression, anxiety and stress compared to controls (p˂0.001). A significantly greater number of FCs (40.00%) reported oral PSDs than control group (12.00%). Most prevalent oral PSD in FCs was aphthous stomatitis followed by oral lichen planus, bruxism, burning mouth syndrome and myofascial pain dysfunction syndrome. Moreover, there was a preponderance of these diseases in FDR (60.86%) compared to SDR (26.08%). FCs with moderate to very severe depression, anxiety and stress showed higher prevalence of these oral PSDs compared to the ones with mild depression, anxiety and stress. CONCLUSION: The observations of higher prevalence of oral PSDs in FCs with psychological alterations can enhance healthcare professionals' awareness to better understand FCs' oral healthcare needs.
.

Oro-facial opportunistic infections and related pathologies in HIV patients: A comprehensive review.

Among all the viral infections, acquired immunodeficiency syndrome (AIDS) is considered as one of the most morbid infections caused by the human immunodeficiency virus (HIV). The prime reason for the pathogenesis is the profound immunosuppression that leads to lethal opportunistic infections (OI), neurological disorders, unexpected malignancies and pathologies of the orofacial region. Patients with OI whose HIV status is unknown have shown a mortality rate higher than those with known HIV status. Among HIV-associated infections, orofacial lesions contribute a major proportion of the OI attributed to the plethora of micro-organisms present in the oral cavity. Apart from serious clinical manifestations, opportunistic infections also lead to significant impairment of quality of life. These lesions not only indicate the HIV infection but also among the clinical manifestations, which often occur early in the course of disease. World Health Organization has also provided policies for treatment/prevention of oral lesions, strengthening the promotion and care of oral health in HIV/AIDS patients. The present review provides comprehensive information about orofacial OI in HIV/AIDS patients and emphasis was also given to the malignancies associated with EB and HTLV virus.

Oral and general health-related quality of life in oral squamous cell carcinoma patients- comparative analysis of different treatment regims.

BACKGROUND: Modern aggressive oncological treatment options for oral squamous cell carcinoma (OSCC) are inevitably associated with impaired general health-related quality of life (HRQoL) and oral HRQoL (OHRQoL). However, there is dire need for prospective and concomitant assessment of HRQoL and OHRQoL after different treatment regims. Hence, present study was designed to investigate HRQoL and OHRQoL in patients treated for OSCC using various modalities. METHODS: 135 OSCC patients were grouped according to treatment rendered into Group A: surgery only; Group B: post-surgical radiotherapy (PRT); and Group C: post-surgical chemo-radiation (PCRT). The 12-item Short Form Health Survey (SF-12) and Oral Health Impact Profile-14 (OHIP-14) were intervened to assess HRQoL and OHRQoL respectively at 1-month and 6-months post-treatment. RESULTS: At 1-month post-treatment, patients who received PCRT showed significantly lower mean values for physical and mental domains of SF-12 and higher mean subscales and overall OHIP-14 (24.57 â€‹± â€‹2.62) score than those treated by surgery alone (10.55 â€‹± â€‹2.26) and PRT (20.20 â€‹± â€‹3.80), with largest differences between PCRT and surgery alone groups (p â€‹< â€‹0.001). Social functioning, general health and bodily pain of SF-12 and functional limitations, physical pain and physical disability amongst OHIP-14 domains were greatly affected. Although few physical domains of SF-12 showed significant improvement, mental domains remained a greater problem after 6 months. However, OHRQoL was significantly poor in all the three study groups (p â€‹< â€‹0.001). CONCLUSION: Irrespective of the post-treatment duration, patients who received PCRT had worse HRQoL and OHRQoL. There is a need to identify factors associated with impaired HRQoL and OHRQoL to customize better therapeutic decisions.

Denture induced mechanotransduction can contribute to oral carcinogenesis.

Mechanical stresses in the form of substrate rigidity, hydrostatic pressure, compressive, tensile and shear stress has been regarded as an important motive for the epithelial carcinogenesis brought about by the activation of Hippo signaling pathways. Masticatory forces generated in edentulous patients with dentures are transferred directly to the palatal mucosa (maxillary denture) and alveolar mucosa (mandibular denture). Thus, the oral mucosa present underneath the dentures experiences compressive, shear and tensile stresses on a day-to-day basis. These stresses can induce carcinogenesis by mechano-transduction and subsequent activation of numerous carcinogenesis relevant signaling pathways such as the HIPPO pathway. With this contention in mind, we proposed a hypothesis, which explains the pathogenesis for the presence of oral squamous cell carcinoma in denture wearer patients. Efforts were made to envisage the appropriate experimentations for the evaluation of the hypothesis. As a therapeutic implication, flexible dentures, soft denture, or medicated dentures could be prescribed for the high-risk groups having potentially malignant lesions in the oral cavity.

Tumor associated tissue eosinophilia in oral squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) still lacks the valid prognosticator for survival. Tumor associated tissue eosinophilia (TATE) have been widely investigated in the literature but still there is no consensus viewpoint on its role as prognostic marker. With this view in mind, a systematic review and meta-analysis of studies that evaluated the overall risk of elevated TATE and survival in OSCC was conducted. METHODOLOGY: A systematic literature search conducted to identify studies that have evaluated TATE in OSCC. Overall survival (OS), Disease Free Survival (DFS) Hazard ratio (HR) with 95% confidence interval) was extracted. HR was extrapolated if direct HR was not given in publication. Studies were pooled and combined hazard ratios (HRs) of High TATE for OS and DFS were calculated. RESULTS: 6 out of 874 articles were found eligible for systematic review and meta-analysis. High TATE was predictor of OS (pooled HR 0.45 (95% CI, 030-0.65, P â€‹< â€‹0.0001)) and DFS (pooled HR 2.33 (95% CI, 0.74-7.37)) in OSCC patients. CONCLUSION: High TATE positively predicts OS and DFS in OSCC and thus can be regarded as an important survival prognosticator. Standardization of counting and reporting methodology for TATE count is recommended on future cohort studies.

Clinical efficacy of mouth exercising devices in oral submucous fibrosis: A systematic review.

BACKGROUND: The management of oral submucous fibrosis (OSF) is primarily focused towards minimizing patient's symptoms and to prevent cancer development. Mouth exercise physiotherapy independently or in combination with other modalities is considered to be a mainstay for increasing the mouth opening (MO). The present systematic review was performed to identify different mouth exercising devices (MEDs) used and to provide detailed information on the fabrication and clinical efficacy of these devices among OSF patients. METHODS: PubMed, Scopus, Web of Science, Google Scholar and CINAHL were searched for relevant literature until February 2019 and the information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All full text papers describing use of MED in OSF patients were considered eligible. RESULTS: Initial search resulted in 88 hits. After removing duplicates and screening of titles and abstracts, five papers that met the inclusion criteria were included. We identified five MEDs used for increasing the MO in OSF patients. Only one study administered additional treatment with topical steroids, oral antioxidants and ice-cream stick regime. The follow-up across studies ranged from 8 weeks to 6 months. Majority of the studies reported significant improvement in the MO without any relapse and side effects. CONCLUSIONS: MED could play an important role in the management of OSF. Limited researches in this area suggest a dire need for the further investigations using randomized controlled trials.

Bibliographic Analysis of Oral Precancer and Cancer Research Papers from Saudi Arabia.

OBJECTIVE: Oral cancer and precancers are a major public health challenge in developing countries. Researchers in Saudi Arabia have constantly been directing their efforts on oral cancer research and have their results published. Systematic analysis of such papers is the need of the hour as it will not only acknowledge the current status but will also help in framing future policies on oral cancer research in Saudi Arabia. METHOD: The search string "oral cancer" OR "Oral Squamous Cell Carcinoma" OR "oral premalignant lesion" OR "oral precancer" OR "Oral Potentially malignant disorder" AND AFFIL (Saudi AND Arabia ) was used for retrieval of articles from Scopus database. Various tools available in Scopus database were used for analyzing the bibliometric related parameters. RESULTS: The search revealed a total of 663 publications based on the above query. Maximum affiliations were from King Saud University (163) followed by Jazan University (109) and then King Abdulaziz University (106). A large number of international collaborations were observed, the maximum with India (176) and the USA (127). The maximum number of articles were published in the Asia Pacific Journal of Cancer Prevention (34) followed by the Journal of Contemporary Dental Practice (33) and Journal of Oral Pathology and Medicine (19). CONCLUSION: Saudi researchers are directing their efforts towards the public health menace of oral cancer. However, it was also observed that some institutions have emerged as front runners in research, whereas others are contributing significantly less. The health department should encourage and take necessary steps to increase the involvement of other institutions.

Histomorphological Evidence of Cellular Cannibalism in Ameloblastoma.

AIM: To study the cellular cannibalism (CC) in the tumor cells of ameloblastoma. MATERIALS AND METHODS: Hematoxylin and eosin (HE)-stained sections of ameloblastoma cases (50) were retrieved from the archived specimens and screened for cellular cannibalism (CC) by stellate reticulum-like cells. Further characterization of CC was performed using CD68 and lysozyme antibodies. RESULTS: CC was observed in 15 (30%) cases [follicular 10 (66.66%), unicystic 3 (20%), and acanthomatous 2 (13.33%)]. In acanthomatous ameloblastoma, the CC was observed in the central metaplastic squamous cells, while in 3 cases of unicystic ameloblastoma, CC was seen in stellate reticulum-like cells of intraluminal (2) and mural proliferations (1). All the 15 cases of ameloblastoma showed a negative expression of CD68 as well as lysozyme. CONCLUSION: CC is a new addition to the pathogenesis of ameloblastoma.

Ki67, CD105 and α-smooth muscle actin expression in disease progression model of oral submucous fibrosis.

AIM: The aim of this study was to investigate the expression of Ki67, CD105 and α-smooth muscle actin (α-SMA) expression in oral submucous fibrosis (OSF) and oral squamous cell carcinoma in the background of OSF (OSCC-SMF). METHODS: The study was carried out on paraffin-embedded tissues of 30 normal oral mucosa (NOM), 50 OSF cases and 105 OSCC-SMF. The immunohistochemistry was carried out to evaluate the expression of Ki67, CD105 and α-SMA antigen. RESULTS: Ki67 labelling index (LI), CD105 and α-SMA expression showed increasing trend from NOM, low-risk epithelial dysplasia (LRED), high-risk epithelial dysplasia (HRED), well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma to poorly differentiated squamous cell carcinoma. However, there was no significant difference of α-SMA expression between HRED and WDSCC. In OSCC-SMF, Ki67 LI, CD105 and α-SMA were significantly higher in advanced clinical TNM stage, metastasis and less than 3 years patient survival as compared with early clinical TNM stage, non-metastasis and 3 years or more patient survival. CONCLUSION: Ki67 LI, α-SMA and CD105 expression alone or together correspond with the disease progression model of SMF. Hence, expression of these markers can be used as a predictive marker of clinical outcome of OSCC-SMF.

Measurement properties of oral health related patient reported outcome measures in patients with oral cancer: A systematic review using COSMIN checklist.

BACKGROUND: Oral cancer (OC) is one of the common malignant neoplasm resulting in a range of debilitating symptoms. Patient reported outcome measures (PROMs) could provide a valuable insight into the impact of OC on patients' quality of life (QoL). Selecting an adequate instrument among available PROMs for OC has been challenging for clinicians due to lack of information on their psychometric quality. This systematic review provides an extensive overview of methodological quality of all currently available PROMs for OC. METHOD: A systematic search was performed in PubMed, Scopus, Web of Science and CINAHL for relevant literature until 10th January 2019 and data was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the identified studies was assessed per measurement property according to the COnsensus-based Standards for the selection of health Measurements Instruments (COSMIN) checklist. RESULTS: Seven studies were found evaluating 6 health-related QoL PROMs. Among six, there were 1 disease-specific and 5 generic PROMs. Information regarding important measurement properties was often incomplete. The evidence for the quality of measurement properties was found to be variable, none of the instruments performed sufficient on all measurement properties. Considering results of this review, QOL-OC appeared to have adequate COSMIN measurement properties. CONCLUSION: QOL-OC can be implemented in future studies to better understand symptoms and expectations of OC patients and help inform clinicians to formulate treatment strategies as per patients' needs.

Oral submucous fibrosis: An enigmatic morpho-insight.

Oral submucous fibrosis (OSMF) is a chronic progressive, scarring disease affecting oral, oropharyngeal, and sometimes the esophageal mucosa. It is characterized by the progressive fibrosis of the submucosal tissue. The pathogenesis of OSMF has been directly related to the habit of chewing areca nut and its commercial preparation, which is widespread in Indian subcontinent and Southeast Asia. The areca nut has been classified as a "group one human carcinogen." Oral squamous cell carcinoma in the background of OSMF is one of the most common malignancies in South and Southeast Asian countries. Malignant transformation has been reported in 7%-12% cases of OSMF. Histopathological spectrum of OSMF includes the apparent alterations observed in the epithelium and connective tissue. Epithelial atrophy and sometimes epithelial hyperplasia with or without dysplasia are the peculiar alterations seen in the epithelium. In the connective tissue, there is extracellular matrix remodeling which results in excessive collagenization. Further cross-linking of collagen leads to hyalinization which makes the collagen resistant to proteolysis. Owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu, that is, hypoxia. This tissue hypoxia elicits angiogenesis which may result in the malignant transformation of OSMF. Perpetual irritation of areca nut and its constituents to the oral mucosa leads to upregulation of pro-inflammatory cytokines and further juxtaepithelial inflammation. Thus, these coordinated reactions in epithelium and connective tissue leads the OSMF toward malignant transformation.

Assessment of oral health-related quality of life instruments for oral submucous fibrosis: A systematic review using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist.

Quality of life (QoL) instruments are becoming increasingly important in research and often used in clinical practice. Various QoL instruments have been developed/ validated for assessment of oral health-related QoL (OHRQoL) in patients with oral submucous fibrosis (OSF). Selection of an adequate instrument is challenging in routine practice due to lack of information on psychometric quality of measurement instruments. This systematic review gives an extensive overview of quality of all the currently available measurement instruments for use in OSF patients. PubMed, Scopus, Web of Science and CINAHL were searched for relevant literature until December 2018 and the information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the identified studies was assessed per measurement property according to the COnsensus-based Standards for the selection of health Measurements Instruments (COSMIN) checklist. Four studies that met the inclusion criteria were included. Three generic and one disease-specific QoL instruments were identified. Information regarding important measurement properties was often incomplete. The evidence for the quality of measurement instruments was found to be variable, none of the instruments performed sufficient on all measurement properties. Based on the available information, OHRQoL-OSF appeared to have adequate COSMIN measurement properties. As recently published, newer QoL instruments have not yet been evaluated in an adequate manner for use in OSF. We suggest future studies should implement OSF-specific OHRQoL-OSF to better understand OSF patients' perspectives and help inform clinicians to propose treatment strategies as per patients' needs.