The Human Papillomavirus Enigma: A Narrative Review of Global Variations in Oropharyngeal Cancer Epidemiology and Prognosis.

Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.

Comparison of the seventh and eighth editions American Joint Committee Cancer classification system in oral cavity squamous cell cancers.

The aim of our study was to evaluate the predictive ability of the American Joint Committee Cancer (AJCC) eighth edition (AJCC8) staging system for oral cavity cancers and validate these changes rendering the hypothesis of improving prognostication. We conducted a retrospective study including all oral cavity squamous cell carcinoma patients visiting our tertiary center from 2012 to 2015, staged as per the AJCC seventh edition (AJCC7) and AJCC8 systems. Stage-specific disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Concordance index (CI) and Akaike information criterion (AIC) were used to calculate the predictive accuracy of the both systems. The study sample consisted of 863 subjects followed up for a median of 24 months. Buccal mucosa complex (BMC) was the most common site (n = 496). We observed a 25.8% (n = 222) overall upstaging in the eighth edition, significantly seen in early tongue cancers (TCs) (Stage I) and advanced BMC cancers (Stage III). An increase in CI and reduction in AIC scores were indicative of a superior predictive accuracy for the eighth edition in assessing DFS (confidence interval [CI*] = 0.650-0.654; AIC = 3,022-3,014) and OS (CI* = 0.643-0.648; AIC = 2089-2086) across all stages. The accuracy was higher for TCs as compared to BMC. Although not statistically significant, we observed an increase in soft risk factors at higher stages in the eighth edition as compared to its predecessor. We concluded that the AJCC8 has a higher predictive accuracy than the AJCC7 edition, making it a reliable prognosticative tool.

Sarcomatoid variant of squamous carcinoma in recurrent and second primary tumors of the oral cavity.

BACKGROUND: Sarcomatoid variant of oral squamous cell carcinoma (OSCC) is aggressive tumors that frequently recur and metastasize. Our aim was to determine the survival outcomes and factors that predict its incidence in recurrent and second primary tumors (SPT). METHODS: We retrospectively analyzed the records of SPT and recurrent OSCC cases with sarcomatoid differentiation. The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method. Logistic regression was used to identify the factors associated with SPT and recurrent sarcomatoid OSCC. Recursive partitioning was performed to classify the sample based on the clinicopathological factors of the index tumor. RESULTS: A total of 82 patients were included in the study with a median survival, calculated from the date of diagnosis of recurrence or SPT, of 6 months (recurrence-2 months, SPT-8 months). The 3-year OS for the recurrence group was 19.9% and for SPT group was 29%. Perineural invasion in the index tumor was significantly associated with sarcomatoid differentiation in the recurrent tumor. At one end of the spectrum of the recursive partitioning were the SPTs that had small index tumor sizes and DOI/thickness less than 14.5 cm (lowest risk), and at the other end were recurrent diseases that had index tumors of advanced T stage (highest risk). CONCLUSION: Sarcomatoid variant in the recurrent/SPT OSCC infers a poor prognosis. Recurrent disease that had an index tumor with advanced T stage carries the worst outcomes. Perineural invasion in the index tumor can help predict the presence of sarcomatoid carcinoma in the recurrent or SPT.

Alcohol and cancer risk: A systematic review and meta-analysis of prospective Indian studies.

BACKGROUND: Alcohol increases risk of cancer of oral cavity and pharynx, esophagus, colorectal, liver, larynx, and female breast. OBJECTIVES: The objective of this study was to determine the relationship of alcohol and cancer in India by meta-analysis. METHODS: Systematic Medline searches were performed to identify all the published literature associating alcohol and cancer in India. Initially, we retrieved 1509 studies, but after applying inclusion and exclusion criteria, only 29 studies were found eligible for our meta-analysis. RESULTS: Our meta-analysis shows that alcohol consumption increases the risk of cancer with the odds ratio (OR) of 2.32 (95% confidence interval [CI]: 1.50-3.47) in case-control studies and relative risk of 1.52 (95% CI: 0.97-2.51) in cohort studies. It also shows that risk of oral cavity cancer increases by two times (OR: 1.92, 95% CI: 1.54-3.96) in the population consuming alcohol. Publication analysis showed that studies included in the meta-analysis had wide variation, suggesting good representation all over the country. CONCLUSION: The result from our meta-analysis supports our hypothesis that alcohol consumption increases the risk of cancer, implying immediate cessation of the habit for cancer risk reduction.

Intraoperative frozen section for detection of occult metastasis in clinically N0 neck does not improve outcome in oral cavity carcinomas.

OBJECTIVE: The objective of this study was to evaluate the utility of frozen section (FS) in detecting occult nodal metastasis in cN0 OSCC and its impact on regional failure and survival. MATERIALS AND METHODS: Clinical records of patients of OSCC operated from January 2013 to December 2014 were retrospectively reviewed. These patients were divided into two groups-Group A comprised of patients who underwent selective neck dissection (SND) (level III/IV) and FS based completion (level IV ± V); Group B included patients who underwent SND I-III/IV without FS. The sensitivity and specificity of FS in detecting occult metastasis was calculated. The regional failure rates and overall survival (OS) between the two groups were compared. RESULTS: The sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of FS in detecting occult metastasis were 64.06%, 100%, 100%, and 92.15%, respectively. There was no significant difference in regional failure rates (p = 0.219) and OS (p = 0.08) between the two groups. CONCLUSION: FS has a poor sensitivity in detecting occult nodal metastasis. FS-guided neck dissection does not have a significant impact in reducing regional failure or improving OS in clinically node-negative neck in oral cavity carcinomas.

Outcome of patients following neo-adjuvant chemotherapy for unresectable cervical nodes in head and neck squamous cell carcinomas.

BACKGROUND: This study was undertaken to assess the effects of neo-adjuvant chemotherapy (NACT) on patients with head and neck squamous cell carcinoma (HNSCC) having advanced unresectable cervical nodal metastasis. METHODOLOGY: A retrospective cohort study was conducted to assess the response of unresectable nodes to NACT in a pragmatic manner. Patients were grouped according to the response noted and the treatment offered after chemotherapy. The median survival amongst the patients in these groups was compared. RESULTS: The study included 51 patients. Oral cavity was the commonest site (67.2%). Favourable nodal response was seen in 64.7% of the patients. Up to 87.9% of the nodal responders were amenable to curative intent therapy. The overall survival of patients undergoing surgery, definitive chemoradiotherapy, palliative chemotherapy and palliative radiotherapy was 24, 13, 10 and 9 months, respectively. CONCLUSION: NACT may be utilized in HNSCC with advanced inoperable nodal disease to make them amenable to definitive therapy.

Survey from 61,748 schools in four States of India on sale of tobacco products near schools.

BACKGROUND: Children form the most vulnerable strata of the society and the tobacco industry is known to target them. Article 16 of the Framework Convention of Tobacco Control (FCTC) calls for prohibition of tobacco sales to and by minors. Although interventions to stop such sales are based on sound science, it is widely acknowledged that many countries find implementation, full of challenges. In India, sales near educational institutions are banned by law, Section 6b of the Cigarettes & Other Tobacco Products Act (COTPA). We conducted a survey of violations in four states [Andhra Pradesh (AP), Karnataka (KA), Meghalaya (ML), Uttar Pradesh (UP)] of India to report the number of violations and to assess if there was an association between the schools with violations and variables such as gender, size, category, location of schools. METHODS: Schools in these States were asked to report the number of shops selling tobacco within 100 yards on an App circulated to all schools (289,392 in number). Chi-square tests, univariate and multivariate logistic regression performed to find association between schools with violations by Category of School, Size of School, Gender of students and location (Urban/Rural). FINDINGS: Responses were received from 61,748 (21.3%) schools of which 16,193 (26.2%) reported violations. It was observed that the percentages of the schools with violations were similar to the prevalence of tobacco usage in the state. Four states AP, KA, ML, UP reported violations 22.2%, 17.5%, 42.9% and 31.4% respectively. On chi-square tests, there was a significant association for the states of KA and ML with regards to variables like size, category, location of schools (p-value <0.001). For AP, all variables were significantly different (p-value <0.001) while for UP variables like size and gender were significant. On logistic regression, there was significant association between the variables like size (>100), category (Upper Primary) and location (urban) for tobacco shops violations in both KA and ML except for the school category that was secondary in ML. While for AP and UP, only size (>100), location (urban) of schools have a significant association with the violations of tobacco shops. Logistic regression of pooled data of four states school size (>100) and school category (primary) and location (urban) had significantly higher association of violation of tobacco shops. INTERPRETATION: This is the first large survey with responses from almost all parts of the four states in India. This study shows significant association with the size, category and location of schools. We anticipate that the lists of schools which have such violations can be used by enforcement agencies to take focused action. Such models will help develop effective tobacco control policies in developing countries with large populations where implementation remains a big challenge.

Prevalence and Malignant Transformation Rate of Oral Erythroplakia Worldwide - A Systematic Review.

Background: To determine the characteristics of oral erythroplakia (OE) on a global scale, it is important to analyse and evaluate findings from various studies conducted across multiple geographical locations. Objectives: This review was conducted to determine the prevalence and malignant transformation rate (MTR) of OE. Data Sources: A systematic search was performed to identify studies reporting the prevalence and MTR of OE across various databases - PubMed, Web of Science, Google Scholar, Elsevier and ScienceDirect without any restriction for the time of publication. Study Eligibility Criteria: This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines, and the protocol was registered in the PROSPERO database (ID: CD42023395215). Results: The prevalence rate of OE reported across the studies ranged from 0.04% to 1.14% with a mean of 0.25 + 0.002%. The MTRs reported across the studies included ranged from 2.6% to 65% with a mean of 30 ± 0.2%. Limitations and Conclusions: Based on the findings from the present review, it can be concluded that while the range of MTRs of OE varies widely across different geographical locations, the average rate can be considered 30%. The review also identified a need for conducting more studies on the prevalence rates as well as longitudinal studies assessing the MTR across different regions.

Surgical management of patients with distant metastasized adenoid cystic carcinoma of the head and neck.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare and malignant tumor of the salivary glands. Despite its slow-growing nature, this clinical entity is notorious for presenting with distant metastasis (DM) which significantly worsens patient outcomes. The role of surgery in patients with ACC and distant metastasis (DM) remains controversial. METHODS: We conducted a retrospective analysis of 47 patients with ACC who underwent surgery for the primary tumor and presented with DM at baseline or developed DM during follow-up. We compared survival outcomes between patients with DM at baseline (Group A) and those who developed DM during follow-up (Group B). RESULTS: The median overall survival (OS) for the entire cohort was 88%. Patients with DM at baseline (Group A) had significantly worse OS (51%) compared to those without DM at baseline (Group B) (91%; P = .04). Local recurrence (LR) was associated with poor survival in both groups. However, salvage surgery for LR+DM was associated with improved OS compared to palliative treatment (100% vs 77%; P = .79). CONCLUSION: Our findings suggest that surgery for the primary tumor of ACC may provide survival benefits in patients with DM. Salvage surgery should be considered particularly for patients who develop local recurrence and distant metastasis during follow-up.

The Trans-facial Approach for Simultaneous Resection and Reconstruction of Retromolar Trigone Tumors: A Pilot Study.

Introduction: Early retromolar trigone (RMT) lesions are difficult to access and free tissue transfer is often an overkill for such small lesions. The aim was to devise a novel surgical approach that would aid the resection without raising a cheek flap and simultaneously provide a local reconstructive option for small lesions in the RMT. Methodology: This study was to demonstrate the outcomes of the "trans-facial" approach used to simultaneously access and reconstruct small RMT tumors through an islanded nasolabial flap. Patients with histologically proven squamous cell carcinoma of RMT requiring surgery were included from January 2021 to September 2022. Case selection was done based on the location of the disease and its size (cT1/T2). All needed bone and soft tissue resection via per oral trans-facial approach, along with an ipsilateral neck dissection. The technique is described along with their post-operative and pathologic outcomes. Results: Out of the eight patients included in this study, six underwent a bi-alveolar marginal resection and reconstructed using the trans-facial approach. No major complications were noted in the post-operative period. 50% were pT1 tumors and 75% were pN0 status. One patient had a close margin; while, the others had adequate resection margins. All patients were followed up for a median of 18 months with a locoregionally controlled status. Conclusion: The trans-facial approach can be a suitable option with a reasonable oncologic outcome to address small RMT lesions.

Effects of Viral Infections Like COVID-19 on Head and Neck Cancers: The Role of Neutrophil-Lymphocyte Counts and Ratios.

BACKGROUND: Over the last three years, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a global impact. COVID-19 has led to diagnostic and treatment delays in head and neck squamous cell cancers (HNSCCs). Both cancer and COVID-19 trigger systemic inflammatory responses that can result in cytokine storms, creating a favorable tumor microenvironment that supports tumor growth. Various studies have shown a positive association between increasing neutrophil-to-lymphocyte ratio (NLR) and disease severity in COVID-19. Studies have also shown that high NLR is associated with poor survival outcomes in cancer patients. Our aim is to investigate whether an increased NLR is linked to rapid tumor progression in patients with HNSCC who have also been affected by infections like COVID-19 in the pre-operative period. METHODS: This was a retrospective analysis of patients of HNSCC who were scheduled for surgery and had contracted COVID-19 in their pre-operative period between April 2021 and May 2021. The study analyzed pre- and post-COVID NLR in relation to disease progression in HNSCC. Statistical analysis was presented as an interquartile range and numbered with the percentage. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY) was utilized for the analysis. RESULTS: We evaluated 200 operable cases of which 38/200 (20%) patients with HNSCC were COVID-19 positive. Out of those COVID-19-positive patients, 27/38 (71%) patients got operated. Around, 11/38 (28.9%) patients were inoperable. And, 14/27 (53.8%) operated patients also had a change in treatment plan. The mean duration from the joint clinic treatment plan to the date of surgery was 25.18 days. Patients who had contracted COVID-19 and had a change in their treatment plan due to disease progression exhibited mean NLR values of 3.84 (pre-COVID) and 11.11 (post-COVID), with respective medians of 3.04 and 10.50. These differences showed a statistically significant p-value of 0.000. In contrast, patients who had no change in treatment plan displayed mean NLR values of 4.51 (pre-COVID) and 9.70 (post-COVID), with respective medians of 3.47 and 3.42, resulting in with a non-significant p-value of 0.082. CONCLUSION: This is a one-of-its-kind study that has evaluated the role of elevated NLR in patients with a COVID-19 virus infection and its relationship with the clinical progression of the disease. The findings suggest that elevated NLR in patients with HNSCC, along with concurrent SARS-CoV2 infection, may contribute to accelerated disease progression with an increase in tumor burden and nodal metastasis.

A Systematic Review and Meta-Analysis of 29 Studies Predicting Diagnostic Accuracy of CT, MRI, PET, and USG in Detecting Extracapsular Spread in Head and Neck Cancers.

BACKGROUND: Extracapsular spread (ECS) is the extension of cancer cells beyond the lymph node capsule and is a significant prognostic factor in head and neck cancers. This meta-analysis compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. METHODOLOGY: The authors conducted a systematic review and meta-analysis of studies that compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. They included studies that were published between 1990 and December 2023 and that used histopathology as the reference standard for ECS. RESULTS: The pooled sensitivity and specificity of CT scan were 0.63 (95% CI = 0.53-0.73) and 0.85 (95% CI = 0.74-0.91), respectively. The pooled sensitivity and specificity of MRI were 0.83 (95% CI = 0.71-0.90) and 0.85 (95% CI = 0.73-0.92), respectively. The pooled sensitivity and specificity of PET were 0.80 (95% CI = 0.74-0.85) and 0.93 (95% CI = 0.92-0.94), respectively. The pooled sensitivity and specificity of USG were 0.80 (95% CI = 0.68-0.88) and 0.84 (95% CI = 0.74-0.91), respectively. MRI had significantly higher sensitivity than CT scan (p-0.05). The specificity of CT and MRI was not significantly different (p-0.99). PET scan had the highest specificity among all imaging modalities. CONCLUSION: MRI is the most accurate imaging modality for detecting ECS in head and neck cancers. CT scan is a reasonable alternative, but PET scan may be considered when high specificity is required. USG may not add any further benefit in detecting ECS.

Prognostic Impact of Poor Differentiation of Squamous Cell Carcinoma in Treatment Naïve Node-Negative Early Oral Cancers.

We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear.

Cross-Sectional and Longitudinal Mental Health Status Prevailing among COVID-19 Patients in Mumbai, India.

Introduction: The aim was to determine the prevalence and predictors of depression among less symptomatic COVID-19 patients. Methods: A questionnaire-based assessment was conducted among asymptomatic or mildly symptomatic COVID-19 patients when admitted in a COVID-19 facility (T1) and after 6 months (T2). Interviews were conducted using the Patient Health Questionnaire-9 instrument. Socio-demographic details and length of facility stay were recorded. Changes in scores between the two-time points T1 and T2 were compared. Factors predicting depression were determined using Chi-square and Mann-Whitney U test during facility stay, and those predicting worsening over time were obtained using multivariate regression models. Results: Among the 91.4% (n = 450) participants, prevalence of depression was 38.4% (95% confidence interval [CI] = 34.0-43.0) with a significant increase of 7.8-fold (95% CI = 4.8-12.8) in depression as the duration of stay increased beyond a median of 5 days. A significant association was observed between higher income and lower depression (odds ratios = 0.6, P = 0.03). 84% (n = 378) responded at the second timepoint assessment after a median of 6.62 months (T2). There was a significant difference observed between the 2.6% (n = 6) that worsened into depression at T2 and the 73.8% (n = 107) that improved out of depression at T2 (P ≤ 0.001). Age >45 years (P = 0.007), males (P = 0.011) and reinfection (P = 0.039) significantly led to worsening of depression. Conclusion: There is a need for actively detecting and managing depression in institutionally quarantined survivors, considering limiting such quarantine to no more than a week, and providing routine screening and care for depression beyond this period.

Survival of Dental Implants on Irradiated Jaws: A Systematic Review and Meta-analysis.

Objectives: Dental implants play a significant role in functional rehabilitation of the oral cavity after debilitating jaw surgeries for oral cavity cancers followed by radiotherapy. Design: The meta-analysis was done using Preferred Reporting Items for Systematic Review (PRISMA) guidelines published from January 1947 till August 2020. Twenty three articles consisting of 1246 participants with 4838 implants were included in our analysis. Results: The mean age of the included participants was 51.4 years. 2186 and 1685 implants were placed on irradiated and non-irradiated jaws and showed a success rate of 82.47% and 89.37% respectively. Correspondingly, publication bias of p value = 0.2129 and p-value = 0.6525 was found by Egger's and Begg's test respectively for pooled data of 16 studies. The implant success rate of 70.4% on maxillary bone and 94.5% were observed on mandibular bone. Timing of implant placement and its influence on survival rate have resulted in a 75.5% survival rate of dental implants when placed primarily in comparison with 87.7% on delayed placement. The waiting interval of 14 months in delayed implant placement has shown better results. Conclusion: Presence of radiotherapy does not play a significant role in the success rate of dental implants in oral cavity cancers. However, delayed implant placement may have a better chance of survival. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-022-01686-6.

A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: Results of an exploratory study (RESCU 004).

Background: Our earlier studies have shown that cell-free chromatin particles (cfChPs) that are released from dying cancer cells are readily internalised by bystander cells leading to activation of two hallmarks of cancer viz. genome instability and inflammation. These hallmarks could be down-regulated by deactivating cfChPs via medium of oxygen radicals generated upon admixing small quantities of the nutraceuticals resveratrol (R) and copper (Cu). In this exploratory study, we investigated whether oral administration of R and Cu (R-Cu) would down-regulate the hallmarks of cancer and immune checkpoints in advanced squamous cell carcinoma of oral cavity (OSCC). Patients and methods: The study comprised of 25 patients divided into 5 equal groups. Five patients acted as controls; the remaining 20 were given R-Cu in four escalating doses. The lowest dose of R-Cu was 5.6mg and 560ng respectively, and the highest dose was 500mg and 5mg respectively. An initial biopsy was taken from patients at first presentation, and a second biopsy was taken 2 weeks later on the operating table. R-Cu was administered orally twice daily in the intervening period. Confocal microscopy was performed on tumour sections after fluorescent immuno-staining with anti-DNA and anti-histone antibodies to detect presence of cfChPs in the tumour micro-environment (TME). Immunofluorescence analysis was performed for 23 biomarkers representing the 10 Hallmarks of cancer, including 5 immune checkpoints, defined by Hanahan and Weinberg. Results: Confocal microscopy detected copious presence of cfChPs in TME of OSCC, which were eradicated/deactivated following two-week treatment with R-Cu. Eradication of cfChPs from TME was associated with marked down-regulation of 21/23 biomarkers, including the five immune checkpoints. The lower two doses of R-Cu were more effective than the higher doses. No adverse effects attributable to R-Cu were observed. Conclusion: These results suggest that cfChPs released into TME from dying cancer cells are global instigators for cancer hallmarks and immune checkpoints in surviving cancer cells. The ability of R-Cu to deactivate cfChPs raises the prospect of a novel and non-toxic form of cancer treatment which sans killing of cancer cells, and instead induces healing by down-regulating cancer hallmarks and immune check-points. Clinical Trial Registration: http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19801&EncHid=&userName=CTRI/2018/03/012459.

A contemporary narrative review to guide molecular epidemiology of oral submucous fibrosis.

Oral submucous Fibrosis (OSMF) is a chronic disease that mainly affects the upper part of the aerodigestive tract. Areca nut and betel quid chewing has been established as the most significant causative factor for this condition. While OSMF is a predominantly Asian disease, the migrant populations from the region have taken the disease across the globe. Additionally, areca nut is now easily accessible in flavors and aggressively marketed. Many research activities have been undertaken for decades to understand the etiopathogenesis and risk factors of OSMF. Although OSMF is a slowly progressing disease, it has the potential to transform to an oral malignancy. This article is an attempt to review the literature and provide an update on its prevalence, etiopthogenesis and its diagnosis. We also highlight certain clinical, histopathological and molecular features that aid in the diagnosis and prognostication of OSMF, highlighting the importance of identifying the possibly high risk OSMF that is prone to malignant transformation. Using this information, future directions can be developed to include treatmentof OSMF through a dynamic gene-specific approach.

Simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, N'-nitrosonornicotine, and cotinine by liquid chromatography-tandem mass-spectrometry.

Biomarkers of exposure to harmful tobacco constituents are key tools for identifying individuals at risk and developing interventions and tobacco control measures. However, tobacco biomarker studies are scarce in many parts of the world with high prevalence of tobacco use. Our goal was to establish a robust method for simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and cotinine at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) in Mumbai, India. These biomarkers are validated measures of exposure to the carcinogenic tobacco nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NNN and the addictive alkaloid nicotine, respectively. The established method is characterized by excellent accuracy, linearity, and precision, and was successfully applied to the analysis of 15 smokeless tobacco (SLT) users and 15 non-users of tobacco recruited in Mumbai. This is the first report of establishment of such procedure in a laboratory in India, which offers the first in-country capacity for research on tobacco carcinogenesis in Indian SLT users.

SARS-Cov2: a meta-analysis of symptom distribution by continent in 7310 adult COVID-19 infected patients.

There is recent evidence that suggests that there are multiple strains of coronavirus in different parts of the world. Moreover, scientist have noted multiple mutations and postulated that these changes might increase the infective rate of the virus. However literature on varying severity of disease based on these strains is absent. In this meta-analysis, we have made an attempt to correlate the symptoms in different continents with respect to various studied strains of virus. We searched three databases, PubMed, EMBASE and EMCARE to identify studies reporting symptoms of COVID-19. All articles published between December 2019 and May 2020 was included in this meta-analysis. A total of 56 studies consisted of 7310 patients were included in the meta-analysis. Mean age of patients varied from 22 to 69.8 years. The pooled proportion of male patients was 52%. Highest incidence of fever (76%) and cough (56%) was noted in Chinese population. Sore throat (29%) was most common in Asian population. Upper respiratory tract symptom like Rhinorrhoea, Anosmia and dysgeusia (32%, 47% and 39%) were well documented in European population as compared to the other continents. Nausea and diarrhoea were more common in European (17%, 19%) and Australian (12%, 16%) population. Dyspnoea and fatigue were consistently similar in all the continents. We postulate that different mutations in COVID-19 virus may vary its pathogenicity and screening symptoms across all the continents should be not be generalised but continent-specific. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00699-y.

A Meta-Analysis of 67 Studies with Presenting Symptoms and Laboratory Tests of COVID-19 Patients.

OBJECTIVES/HYPOTHESIS: The objective of this meta-analysis was to look at the pooled prevalence of symptoms, laboratory tests, and imaging of all COVID-19 infected patients. This will allow better identification of potential COVID-19 patients and take appropriate precautions. STUDY DESIGN: Meta analysis. METHODS: We searched three databases, PubMed, EMBASE, and Ovid to identify studies published between Dec-2019 and May-2020. All studies reporting upper-aerodigestive symptoms of COVID-19 infection were included. The meta-analysis was conducted following meta-analyses of observational studies in epidemiology (MOOSE) guidelines, which have evaluated the pooled prevalence of 14 symptoms and nine laboratory investigations. RESULTS: Based on inclusion criteria, 67 publications consisting of 8302 patients were included. Among adults, the pooled proportion of hypertensive and diabetic patients was 18% and 7%. Cough (53% [0.46-0.61]), anosmia (38% [0.19-0.58]), loss/distortion of taste (31% [0.17-0.45]), and nasal obstruction (26% [0.12-0.39]) were the most common ear, nose & throat (ENT) symptoms. Fever (69% [0.62-0.76]) and fatigue (31% [0.26-0.37]) were the commonest generalized symptoms. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were raised in 56% (0.41-0.71) and 49% (0.21-0.77), respectively. Interestingly, lymphopenia (41% [0.30-0.53]) and leucopenia (22% [0.16-0.29]) were more common than lymphocytosis (33% [0.02-0.64]) and leucocytosis (12% [0.09-0.16]). Fever (69% vs. 44%), cough (53% vs. 33%), and dyspnea (20% vs. 4%) were more common in adults as compared to the pediatric population. Diarrhea was more common among the pediatric cases (12%) versus (9%). The pooled estimate of fatality was 4%. CONCLUSIONS: The most commonly experienced ENT symptom was cough followed by anosmia and dysguesia. Raised ESR and CRP with leukopenia and lymphopenia are common laboratory findings. Majority of the infected patients had abnormal computed tomography findings. COVID infection is less severe in pediatric patients. Laryngoscope, 131:1254-1265, 2021.