N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer?

AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.

A prospective health economic evaluation to determine the productivity loss due to premature mortality from oral cancer in India.

INTRODUCTION: India contributes two-thirds of the global mortality due to oral cancer and has a younger population at risk. The societal costs of this premature mortality are barely discussed. METHODS: Using the human capital approach, we aimed to estimate the productivity lost due to premature mortality, valued using individual socioeconomic data, related to oral cancer in India. A bottom-up approach was used to prospectively collect data of 100 consecutive patients with oral cancer treated between 2019 and 2020, with a follow-up of 36 months. RESULTS: The disease-specific survival for early and advanced stage was 85% and 70%, with a median age of 47 years. With 671 years lost prematurely, the loss of productivity was $41 900/early and $96 044/advanced stage. Based on population level rates, the total cost of premature mortality was $5.6 billion, representing 0.18% of GDP. CONCLUSION: India needs to implement tailored strategies to reduce the economic burden from premature mortality.

Outcome of early detection approach in control of breast, cervical, and oral cancer: Experience from a rural cancer center in India.

In low- and middle-income countries most of the cancer patients attend the hospital at a late stage and treatment completion of these cases is challenging. The early detection program (EDP), in rural areas of Punjab state, India was initiated to identify breast, cervical, and oral cancer at an early stage by raising awareness and providing easy access to diagnosis and treatment. A total of 361 health education programs and 99 early detection clinics were organized. The symptomatic and self-interested (non-symptomatic individuals who opted for screening) cases visited the detection clinic. They were screened for breast, cervical, and/or oral cancer. Further diagnosis and treatment of screen-positive cases were carried out at Homi Bhabha Cancer Hospital (HBCH), Sangrur. Community leaders and healthcare workers were involved in all the activities. The EDP, Sangrur removed barriers between cancer diagnosis and treatment with the help of project staff. From 2019 to 2023, a total of 221,317 populations were covered. Symptomatic and self-interested individuals attended the breast (1627), cervical (1601), and oral (1111) examinations. 46 breast (in situ-4.3%; localized-52.2%), 9 cervical (localized-77.8%), and 12 oral (localized-66.7%) cancer cases were detected, and treatment completion was 82.6%, 77.8%, and 50.0%, respectively. We compared cancer staging and treatment completion of cases detected through EDP with the cases attended HBCH from Sangrur district in 2018; the difference between two groups is statistically significant. Due to the early detection approach, there is disease down-staging and improvement in treatment completion. This approach is feasible and can be implemented to control these cancers in low- and middle-income countries.

Areca nut and oral cancer.

INTRODUCTION: The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health. GLOBAL PERSPECTIVE: Areca nut, often chewed in various forms such as betel quid, is deeply rooted in cultural practices across Asia and other parts of the world. Epidemiological studies consistently reveal a significant correlation between areca nut use and the incidence of oral cancer, emphasizing the need for targeted preventive measures. The complex interplay of areca nut's bioactive compounds, particularly arecoline, with cellular processes, contributes to the initiation and progression of oral carcinogenesis. Mechanistic insights into the genotoxic and cytotoxic effects of its components underscore the urgency for comprehensive public health interventions. PUBLIC HEALTH: Efforts to address this public health challenge involve multidisciplinary approaches, encompassing education, policy implementation, and behavioral interventions. Understanding the socio-cultural factors influencing areca nut consumption is pivotal for designing effective awareness campaigns and cessation programs. CONCLUSION: As oral cancer remains a significant global health burden, unraveling the nuanced relationship between areca nut and its role in oral carcinogenesis is crucial for advancing preventive strategies and mitigating the impact of this modifiable risk factor.

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.

Swallowing in advanced oral cancers: A prospective observational study.

BACKGROUND: Advanced head and neck cancers are known to cause swallowing dysfunction due to anatomical and post-treatment changes. Literature is sparse on post-surgical and/or multi-modality therapy-associated swallowing function in advanced oral cancers. We conducted this study to longitudinally assess and compare the pre- and post-therapy swallowing dysfunction associated with locally advanced oral cancers. METHODS AND MATERIAL: A prospective observational longitudinal study was conducted at a tertiary cancer center from 2017 to 2018 including treatment-naive cT4a oral cancer patients (AJCC 7th edition). The assessment was done pre-surgery, post-surgery, and post-adjuvant setting as per the scales (Dysphagia score, Penetration aspiration scale, and Yale pharyngeal residue (vallecular and pyriform fossa). RESULTS: Of the 30 patients in the study, 47.4%, 47.4%, 52.6%, and 47.4% experienced deterioration of Dysphagia score, Penetration-Aspiration Scale (PAS), vallecula residue, and pyriform residue scores in the postoperative period. And 52.6%, 47.4%, 68.4%, and 57.9% had inferior dysphagia score, PAS, vallecula, and pyriform residue scores even 6 months after completion of adjuvant therapy. The dysphagia score correlated well with other objective assessment scores at different time points. CONCLUSION: Swallowing functions are significantly affected by surgery and adjuvant therapy and continue to be affected even 6 months after completion of treatment. Appropriate rehabilitation and intervention must be offered to patients to reduce this problem. Dysphagia scores can predict the swallowing status similar to other objective assessments.

A hospital-based study of survival in oral cancer patients of Tata Memorial Hospital, Mumbai.

Introduction: Oral cancer represents a significant global public health concern, with the death rate for lip and oral cavity malignancies experiencing a 1.40-fold increase worldwide in the past three decades. This retrospective study aimed to comprehensively understand overall survival (OS) and the influence of sociodemographic and clinical factors on patients diagnosed with oral cavity cancer. Materials and methods: The study focused on oral cancer patients enrolled in 2016 and treated at Tata Memorial Hospital, Mumbai, with a follow-up period extending to 5 years until 2021. Utilising the Kaplan-Meier technique and log-rank test, we examined OS and variations based on sociodemographic factors, while the Cox proportional hazard model allowed us to investigate the simultaneous impact of multiple factors on OS. Results: A total of 1,895 eligible participants were included. The overall 5-year survival rate was 65%. After adjusting for age, gender, education, primary site, tumour grade, TNM staging, treatment intention, status and modality, we found in our study oral cancer patients aged more than 60 years (HR = 1.37, 95% CI: 1.01-1.85, p-value 0.03), patients who had poorly differentiated carcinoma (HR = 2.44, 95% CI: 1.56-3.81, p-value < 0.001), belonged to stage IV as per TNM staging (HR = 2.44, 95% CI: 1.65-3.61, p-value < 0.001), patient who have received partial treatment (HR = 2.44, 95% CI: 1.65-3.61, p-value < 0.001) and only chemotherapy (HR = 3.56, 95% CI: 2.43-5.23, p-value < 0.001) found to have a higher hazard of dying while literate (HR = 0.73, 95% CI: 0.56-0.95, p-value 0.02) are protective. Limitations: The retrospective nature of the study posed constraints in exploring additional variable associations. Implication: Overall early detection, appropriate treatment, and regular follow-up are critical for improving the survival rate of patients with oral cavity cancer. Conclusion: This research proposes that improving the socioeconomic status and promoting proactive treatment-seeking behaviour is crucial for enhancing the survival of oral cancer patients. Cancer hospitals, in collaboration with the wider public healthcare system in India, which includes clinicians and policymakers, should consider these suggestions to enhance cancer treatment and control in low-middle-income countries.

Rural-urban disparity in cancer burden and care: findings from an Indian cancer registry.

BACKGROUND: Cancer incidence and mortality vary across the globe, with nearly two-thirds of cancer-related deaths occurring in low- and middle-income countries. The rural-urban disparity in socio-demographic, behavioural, and lifestyle-related factors, as well as in access to cancer care, is one of the contributing factors. Population-based cancer registries serve as a measure for understanding the burden of cancer. We aimed to evaluate the rural-urban disparity in cancer burden and care of patients registered by an Indian population-based cancer registry. METHODS: This study collected data from Varanasi, Uttar Pradesh, India, between 2017 and 2019. Sex and site-specific age-standardised rates for incidence and mortality per 100,000 population were calculated. Rural-urban disparities in cancer incidence and mortality were estimated through rate differences and standardised rate ratios (with 95% confidence intervals). Univariable and multivariable regressions were applied to determine any significant differences in socio-demographic and cancer-related variables according to place of residence (rural/urban). Crude and adjusted odds ratios with 95% confidence intervals were calculated. RESULTS: 6721 cancer patients were registered during the study duration. Urban patients were older and had better literacy and socioeconomic levels, while rural patients had higher odds of having unskilled or semi-skilled professions. Diagnostic and clinical confirmation for cancer was significantly higher in urban patients, while verbal autopsy-based confirmation was higher in rural patients. Rural patients were more likely to receive palliative or alternative systems of medicine, and urban patients had higher chances of treatment completion. Significantly higher incidence and mortality were observed for oral cancer among urban men and for cervical cancer among rural women. Despite the higher incidence of breast cancer in urban women, significantly higher mortality was observed in rural women. CONCLUSIONS: Low- and middle-income countries are facing dual challenges for cancer control and prevention. Their urban populations experience unhealthy lifestyles, while their rural populations lack healthcare accessibility. The distinctness in cancer burden and pattern calls for a re-evaluation of cancer control strategies that are tailor-made with an understanding of urban-rural disparities. Context-specific interventional programmes targeting risk-factor modifications, cancer awareness, early detection, and accessibility to diagnosis and care are essential.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

Role of imaging in the management of thyroglossal duct cyst carcinomas (TGC-TIRADS): a single centre retrospective study over 16 years.

Introduction: Thyroglossal duct cyst (TGDC) is the most frequently encountered developmental anomaly in thyroid genesis with a reported incidence of 7% in the adult population. The cyst is known to develop anywhere along the pathway of thyroid descent but is more frequently seen in the infrahyoid neck in the midline. The incidence of malignancy in a TGDC is approximately 1%; a majority of these are papillary carcinomas. This study was conducted at a single tertiary care centre which spanned over a decade which adds practice changing evidence-based knowledge to existing literature on this rare entity. A comprehensive study which conclusively establishes the imaging features predictive of malignancy in TGDC carcinomas (TGDCa), the protocol for optimal management, clinical outcome and long-term survival of these patients is not available. Although TGDC carcinoma is thought to have an excellent prognosis, there is not enough data available on the long-term survival of these patients. The aim of this study was to identify whether neck ultrasound (US) can serve as an accurate imaging tool for the preoperative diagnosis of TGDC carcinomas. Methods: We accessed the electronic medical records of 86 patients with TGDC between January 2005 to December 2021. Of these, 22 patients were detected with TGDC papillary carcinoma on histopathologic examination. Relevant imaging, treatment and follow up information for all cases of TGDC carcinoma were retrospectively reviewed. We compared US characteristics predictive of malignancy across outcomes groups; malignant vs benign using the Chi-square test. Based on the results, a TGC-TIRADS classification was proposed with calculation of the percentage likelihood of malignancy for each category. Results: Compared to benign TGDCs, malignant TGDCs were more likely to present with following US characteristics: irregular or lobulated margins (90.40 vs. 38.10%), solid-cystic composition (61.90 vs. 17.07%), internal vascularity (47.62 vs. 4.88 %), internal calcification (76.19 vs. 7.32 %) (each p value < 0.005). Calcifications and internal vascularity were the most specific while irregular/lobulated margins were the most sensitive feature for malignancy. AUC under the ROC curve was 0.88. Allpatients were operated and were disease free at the end of 5 years or till the recent follow up. Discussion: US is the imaging modality of choice for pre-operative diagnosis of TGDC carcinoma. Thepre-operative diagnosis and risk stratification of thyroglossal lesions will be aided by the application of the proposed TGC-TIRADS classification, for which the percentage likelihood of malignancy correlated well with the results in our study. Sistrunk procedure is adequate for isolated TGDC carcinoma; suspicious neck nodes on imaging also necessitates selective nodal dissection. Papillary carcinomas have an excellent prognosis with low incidence of disease recurrence.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

Malignant Minor Salivary gland neoplasms ofLarynx: Our Experience.

<br><b>Introduction:</b> Malignant minor salivary gland tumors are rare, accounting for fewer than 1% of all laryngeal cancers.</br> <br><b>Aim:</b> This study aims to share our experiences regarding clinical, radiological, pathological profiles and their management.</br> <br><b>Materials and methods:</b> The current study reviews 11 cases of malignant minor salivary gland tumors of the larynx treated surgically at our Institute between 2005 and 2019.</br> <br><b>Results:</b> The mean age of the patients was 54 years (range 38-75 years) with six females and five males in the series (1.2:1). Subglottis and trachea were the sites of origin in 54% of the cases, and hoarseness with dyspnea were the most common presenting symptoms. There were nine Adenoid cystic and two Mucoepidermoid carcinoma patients. Surgery was the primary mode of treatment.</br> <br><b>Conclusions:</b> Most of the larynx's malignant minor salivary gland tumors are submucosal in origin. The outcome and prognosis vary considerably based on the tumor's histology, grade, and stage.</br>.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Objective: Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Methods: Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Results: Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. Conclusion: The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Head and neck cancer burden in India: an analysis from published data of 37 population-based cancer registries.

Head and neck cancer (HNC) is a major public health problem in India. This article presents the HNC burden in different regions of India. The published population-based cancer registries (PBCRs) data from the National Cancer Registry Programme, Bengaluru, and the Tata Memorial Centre, Mumbai, India, were utilised. The 37 PBCRs were divided into six regions including central, east, north, northeast, west and south. The age-standardised incidence rate of HNC was 25.9 (95% CI 25.7-26.1) and 8.0 (95% CI 7.9-8.1) per 100,000 population, respectively, in males and females. HNC accounted for about 26% of all cancer cases in males and 8% in females. The risk of developing HNC was 1 in 33 for males and 1 in 107 for females. The northeastern registries reported the highest incidence rate 31.7 per 100,000 population in males followed by northern (28.5), central (28.3), western (24.4), southern (23.9) and eastern (18.3). In females, the incidence was in the range of 6.2-10.1 per 100,000 population. For all PBCRs together, the HNC burden was two to three times higher in the age group 60+ as compared to 20-39 years. The HNC burden in India is higher than in the USA, UK, Australia, Africa and Brazil. The PBCRs from the south-east Asia region such as the Colombo district, Sri Lanka, as well as Siraha, Saptari, Dhanusha and Mohattari - Nepal have also reported a high burden of HNC. All regions reported mouth as a leading cancer site followed by tongue, larynx, hypopharynx and tonsil except the northeastern region registries where hypopharynx was the top leading cancer. The burden of other sites of HNC is low. Raising awareness of the disease and associated risk factors, providing early detection services, as well as easy access to diagnosis and treatment are required. The government should focus on building the infrastructure and capacity building to control this disease.

The Regenerative Power of Stem Cells: Treating Bleomycin-Induced Lung Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no known cure, characterized by the formation of scar tissue in the lungs, leading to respiratory failure. Although the exact cause of IPF remains unclear, the condition is thought to result from a combination of genetic and environmental factors. One of the most widely used animal models to study IPF is the bleomycin-induced lung injury model in mice. In this model, the administration of the chemotherapeutic agent bleomycin causes pulmonary inflammation and fibrosis, which closely mimics the pathological features of human IPF. Numerous recent investigations have explored the functions of various categories of stem cells in the healing process of lung injury induced by bleomycin in mice, documenting the beneficial effects and challenges of this approach. Differentiation of stem cells into various cell types and their ability to modulate tissue microenvironment is an emerging aspect of the regenerative therapies. This review article aims to provide a comprehensive overview of the role of stem cells in repairing bleomycin-induced lung injury. It delves into the mechanisms through which various types of stem cells, including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and lung resident stem cells, exert their therapeutic effects in this specific model. We have also discussed the unique set of intermediate markers and signaling factors that can influence the proliferation and differentiation of alveolar epithelial cells both during lung repair and homeostasis. Finally, we highlight the challenges and opportunities associated with translating stem cell therapy to the clinic for IPF patients. The novelty and implications of this review extend beyond the understanding of the potential of stem cells in treating IPF to the broader field of regenerative medicine. We believe that the review paves the way for further advancements in stem cell therapies, offering hope for patients suffering from this debilitating and currently incurable disease.

Mitochondria in Cancer Stem Cells: From an Innocent Bystander to a Central Player in Therapy Resistance.

Cancer continues to rank among the world's leading causes of mortality despite advancements in treatment. Cancer stem cells, which can self-renew, are present in low abundance and contribute significantly to tumor recurrence, tumorigenicity, and drug resistance to various therapies. The drug resistance observed in cancer stem cells is attributed to several factors, such as cellular quiescence, dormancy, elevated aldehyde dehydrogenase activity, apoptosis evasion mechanisms, high expression of drug efflux pumps, protective vascular niche, enhanced DNA damage response, scavenging of reactive oxygen species, hypoxic stability, and stemness-related signaling pathways. Multiple studies have shown that mitochondria play a pivotal role in conferring drug resistance to cancer stem cells, through mitochondrial biogenesis, metabolism, and dynamics. A better understanding of how mitochondria contribute to tumorigenesis, heterogeneity, and drug resistance could lead to the development of innovative cancer treatments.