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Summary Background: Thyroid cancer (TC) is the most common endocrine cancer and has been increasing over the past decades worldwide. A notable finding is that Kerala's capital Thiruvananthapuram ranks the first among men and the second highest among women in the incidence of TC in India. Reasons for this increase have not been established. Objectives: Here, we investigated the spatiotemporal pattern of TC incidence in Thiruvananthapuram. Materials and Methods: TC incidence data (n = 1937) of Population Based Cancer Registry Thiruvananthapuram, Kerala, India, between 2012 and 2016, were analyzed for identifying geographical patterns by spatial methods, temporal methods for studying spatial variation in TC incidence, distribution of age, gender, and histology in lowland (coastal), midland, and highland. Results: Spatial clustering of TC incidence was identified consistently near the coastal region based on all geospatial analyses. 56.9%, 23.9%, and 19.2% of TC cases were observed in the coastal, midland, and highland areas, respectively. A significant clustered pattern of TC incidence was revealed by Moran's index I (0.49), high-high clusters by local Moran's, hotspot by Getis-Ord-Gi* (P < 0.05), point pattern analysis by nearest neighbor ratio and kernel density estimation. The relative risk of the significant cluster was obtained as 1.60 (95% confidence interval: 1.03-1.84) by SaTScan analysis. Conclusion: This study identified spatial variations in the pattern of TC cases with significant clusters near the coastal region of Thiruvananthapuram. This would help to pinpoint the high-risk geographical areas of TC and for more effective cancer control programs.

Background: The majority of local relapses after breast conservation therapy occur in the proximity of the primary lesion. Studies have shown that boost radiotherapy (RT) following conventional whole-breast radiotherapy (WBRT) of 50 Gy in five weeks improves outcomes. Boost RT also increases the risk of moderate skin reactions and fibrosis. The ideal boost RT dose and timing (sequential versus simultaneous) after hypofractionated radiotherapy schedules remain unclear. This retrospective propensity score-matched analysis assessed the outcome of sequential hypofractionated boost compared to conventional fractionated boost.Methods: The study was approved by the Institutional Review Board of the Regional Cancer Centre, Thiruvananthapuram, India. Patients with stage I-III breast cancer who have received adjuvant radiotherapy with a sequential boost of either hypofractionated RT (8 Gy in three fractions) or conventional fractionated RT (10 Gy in five fractions) after conservative breast surgery were identified from the radiotherapy planning records and included in this study. A 1:1 case matching was performed using a propensity score incorporating four known prognostic factors, namely, clinical and pathological composite stage, tumor grade, tumor biology (based on estrogen and/or progesterone and HER2 neu expression), and boost technique, which may have an impact on acute toxicity to make the two boost groups more homogenous.Results: After propensity score matching (PSM), there were a total of 166 patients, with 83 patients each in both conventional and hypofractionated boost RT groups. The median follow-up period was 30.7 months. At two years, locoregional recurrence-free survival (LRFS) was 98.8% in both groups. Disease-free survival (DFS) at two years for the hypofractionated group and conventional group was 91.5% and 96.3% (hazard ratio (HR): 2.5, 95% confidence interval (CI): 0.664-9.4, p = 0.161), respectively, with no statistically significant difference. Patients with grade 3 tumors who received hypofractionated boost had a statistically significant increased risk of recurrence (DFS: 88.9% versus 100%, HR: 60.559, 95% CI: 0.138-26613.2, p = 0.011). The overall survival (OS) at two years was 100% in both groups. There was no difference in acute skin toxicity between the two groups.Conclusion: The present interim analysis shows similar locoregional recurrence-free survival, overall survival, and disease-free survival and acute skin toxicity for hypofractionated boost RT of 8 Gy in three fractions compared to the conventional boost of 10 Gy in five fractions. Hypofractionated boost is a feasible alternative option following hypofractionated whole-breast radiotherapy for women with breast conservation treatment. However, longer follow-up is required before forming definite conclusions.

•The present manuscript aims to assess the transition of cancer pattern in the populations in India during the past 30 years.•Cancer burden in India is the third highest number globally after China and USA.•The present analysis of assessing the transition of cancer according to the changes in demographic and epidemiologic risk factors is first of its kind. An assessment of transition of cancer in India during the past 30 years, according to changes in demographic and epidemiologic risk factors was undertaken. Cancer registry data (http://www.ncdirindia.org), (population coverage <10%), was compared with transition in life-expectancy and prevalence on smoking, alcohol and obesity. We fitted linear regression to the natural logarithm of the estimated incidence rates of various cancer registries in India. Burden of cancer in India increased from 0.6 million in 1991 to 1.4 million in 2015. Among males, common cancers are lung (12.0%), mouth (11.4%), prostate (7.0%), and tongue (7.0%) and among females, they are breast (21.0%), cervix-uteri (12.1%), ovary (6.9%), and lung (4.9%) in 2012. Increased life-expectancy and population growth as well as increased use of alcohol and increased prevalence of overweight/obesity reflected an increase in all cancers in both genders except a reduction in infection-related cancers such as cervix-uteri and tobacco-related cancers such as pharynx (excludes nasopharynx) and oesophagus. Transition in demographics and epidemiologic risk factors, reflected an increase in all cancers in both genders except a reduction in a few cancers. The increasing incidence of cancer and its associated factors demands a planned approach to reduce its burden. The burden assessment needs to be strengthened by increasing the population coverage of cancer registries. Continued effort for tobacco prevention and public health efforts for reducing obesity and alcohol consumption are needed to reduce the cancer burden.

Abstract Background: Oral cancer is a major health problem in India. Recently an increase in the oral cancer incidence among young individuals without any habits was observed, which may be due to Human Papilloma Virus (HPV). However, information on the prevalence of HPV in oral cancer in India is sparse. This study aims to document the frequency of HPV16 infection in oral squamous cell carcinoma (SCC) and to study its correlation with treatment outcome. Methods: Paraffin-embedded tissue blocks of 183 patients with SCC of the oral cavity were studied. HPV16 prevalence was detected by a polymerase chain reaction and expression of p16INK4a was analyzed by immunohistochemistry. This was correlated with clinical outcomes. Results: The prevalence of HPV 16 was 6.6% and all were carcinoma tongue. All HPV-positive patients showed intense expression of p16INK4a. The five-year overall survival (OS) and disease-free survival (DFS) for HPV positive patients were higher compared to HPV negative patients (100% versus 74.5% and 100% versus 70.8% respectively). The five-year OS and DFS for patients with p16INK4a intense expression were also higher compared to p16INK4a weak expression (91.2% versus 57.4% and 82% versus 22.5% respectively). Five-year OS and DFS of patients with HPV16 positivity and p16INK4a intense expression were significantly higher than patients with HPV negative and p16INK4a weak expression (100% versus 54.7% and 100% versus 22.5% respectively). Conclusion: The frequency of HPV16 positivity in oral cancer was low in this study with a site predilection to the oral tongue. p16INK4a expression did not correlate with HPV status. A better treatment outcome was observed in HPV-positive cancers. We also observed better treatment outcomes in patients with p16INK4A overexpression irrespective of HPV status.

Reconstruction of a paediatric bone tumour after wide excision is challenging. Autologous sterilized tumour bone provides a perfect fit, avoids wear and tear of the prosthesis, and promises longevity of reconstruction. Here we present our experience on wide excision and reconstruction with irradiated tumour bone at our institution which is a high-volume paediatric sarcoma care centre. This is a retrospective analysis of 53 paediatric patients who underwent reconstruction with irradiated tumour bone between 01/01/2011 and 31/12/2021. The median follow-up period was 64 months (6–112 months) and 83.3% of patients had a minimum follow-up of 3 years. There were 44 diaphyseal osteotomies and 42 metaphyseal osteotomies. Short-term complications were seen in ten patients (18.9%). The long-term complications were high, but 65% of cases were successfully managed and at the time of analysis, only 15 patients had morbidity related to long-term complications. A total of seven patients (13.2%) had persistent nonunion even after additional procedures like bone grafting and refixation. There were four isolated local recurrences in our series (7.5%), and all of these occurred in the soft tissue. The 5-year overall survival was 75.7%, and 5-year disease-free survival was 63%. Reconstruction with irradiated tumour bone is an oncologically safe procedure with acceptable morbidity. Although it is not a procedure without complications, it is an excellent option for reconstruction in paediatric bone tumours.

Introduction The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing worldwide. High-risk human papillomavirus (HPV) infection is now a well-recognised risk factor for oropharyngeal cancers. However, the information regarding the prevalence and outcome of HPV-related OPSCC is sparse in India. The study was conducted to identify the frequency of HPV infection in oropharyngeal cancer and also to study the treatment response and survival according to HPV positivity and p16 expression. Materials and methods The study sample consists of 100 paraffin-embedded tissue blocks of histologically proven OPSCC patients who had undergone treatment at a tertiary cancer centre in Kerala, India, from January 2010 to December 2012. The patients' medical records were examined to obtain demographic data, information on habits, and clinical, histopathological, and treatment information. Follow-up information on disease status and vital status was collected until May 2023. Paraffin-embedded tissue blocks of these patients were collected from the archives of the Division of Pathology. Immunohistochemistry (IHC) was used to identify p16 expression. HPV DNA was isolated from the paraffin-embedded tissue blocks by polymerase chain reaction. Statistical analysis and results Survival curves were obtained using the Kaplan-Meier method and compared with the log-rank test. The influence of p16 status and HPV DNA positivity on survival and recurrence was assessed using Cox regression. A total of 100 patients diagnosed with oropharyngeal malignancy and their paraffin-embedded blocks were used for the present study. p16 IHC was invalid for three patients, and 16 patients had invalid HPV DNA. Two patients were excluded from survival analysis because they had both invalid HPV DNA and p16 expression. A total of 98 patients were included in the analysis. Out of 98 samples assessed, 47 tested positive for p16 expression, 48 were negative, and three showed invalid results. Among the 98 patients, HPV DNA results were available for 82 patients. HPV DNA positivity was reported in 25 patients, and 57 samples were HPV negative. There was no significant correlation between p16 expression and HPV status. The median follow-up was 134 months (1-160 months). The five-year overall survival (OS) probability was 42.6% (95% confidence interval (CI) 28.49-56.71) and 51.2% (95% CI 35.92-66.48), respectively, for p16-negative and p16-positive tumours (p=0.689). The corresponding figures for five-year disease-free survival (DFS) were 49.0% (95% CI 34.7-63.3) and 51.9% (95% CI 36.62-67.18), p=0.959. The five-year OS for HPV DNA-negative tumours was 45.5% (95% CI 32-59.02) compared to 49.1% (95% CI 28.72-69.48) in HPV DNA-positive tumours. There was an absolute difference of 20% in five-year OS between double-positive and double-negative tumours. Conclusion This study demonstrated a p16 positivity rate of 49.47% and an HPV DNA positivity rate of 30.37%. However, only 15.18% of cases showed double positivity. No significant correlation was observed between p16 expression and HPV status. Double positivity (p16 and HPV positive) was associated with better OS and DFS compared to double-negative (p16 and HPV negative) and single-positive (either p16 positive or HPV positive) cases. This subgroup of patients might benefit from potential de-escalation strategies and should be the target population for future studies.

Oral diseases like periodontitis and mucositis often require home care using topical agents in the form of mouthwashes. Many herbal mouthwashes are found to be beneficial; however lack proper scientific evidence to support their use. Study 1 evaluated clinical efficacy of herbal mouthwash in the management of chronic periodontitis in comparison with chlorhexidine mouthwash. Study 2 aimed at assessment of herbal mouthwash in patients of radiation-induced mucosititis. The novel herbal mouthwash used in the present study wa prepared from extracts of five plants namely Emblica Officinalis, Terminalia chebula, Terminalia bellerica, Glycyrrhiza glabra, and Azadirachta indica. 50 periodontitis patients were randomly allocated to two groups. As per allocation, they were instructed to use either herbal mouthwash or chlorhexidine mouthwash twice daily for two weeks after nonsurgical periodontal therapy. Similarly, patients with radiation-induced mucositis were randomly given herbal mouthwash and soda saline mouthwash. Intergroup and intragroup comparisons of continuous variables were conducted using paired and unpaired t-tests. Categorical variables were compared using the chi-square test. Significant reductions in gingival bleeding, plaque accumulation, and pocket depth were noticed in periodontitis patients in both groups. Patients reported acceptable taste, freshness, and satisfaction after the use of herbal mouthwash. The herbal mouthwash group noticed a significant reduction in the severity of radiation-induced mucositis and analgesic requirements. The intensity of pain, dryness of mouth, oral hygiene, and need for the use of antibiotic and antifungal during radiotherapy was not significant among the groups. The results of this preliminary clinical trial support the use of the tested herbal formulation mouthwash as an adjunct in the treatment of periodontitis as well as radiation-induced mucositis. For Study 1: CTRI/2019/10/021574, Study 2: CTRI/2020/04/024851.

Epstein-Barr virus (EBV) DNA quantification in nasopharyngeal cancer (NPC) is an indicator of the tumour burden, stage and survival. Although EBV dynamics in endemic regions has been extensively studied and reported, the data from non-endemic regions is sparse. This study attempts to investigate the EBV dynamics in NPC patients from a non-endemic region and also to identify the factors impacting the outcomes. This was a prospective observational study conducted at a tertiary care centre in South India and enrolled patients with non-metastatic, biopsy proven NPC, who were suitable for radical chemo-radiotherapy with or without induction chemotherapy. Two blood samples, one prior to initiation of any anticancer treatment, and second at 6 weeks post treatment, were collected to quantify EBV DNA using real-time quantitative polymerase chain reaction. Antibodies against EBV viral capsid antigen (EBV VCA IgM), EBV Early Antigen (EBV EA IgG) and EBV Nuclear Antigen (EBV EBNA IgG) were also measured in the sample. The impact of EBV dynamics on the outcomes was then analysed. The study included a total of 35 patients. Thirty-three had identifiable EBV DNA (94.3%) and a histological diagnosis of non-keratinising undifferentiated type of squamous cell carcinoma. There was no correlation between the EBV DNA and anti-EBV antibodies. There was a significant association between composite stage and pre-treatment DNA titre ( = 0.030). The mean EBV DNA titre was lower for patients with no clinically demonstrable disease at last follow-up and the reduction in EBV DNA titres was significant ( = 0.020) for those patients who remained disease free. Plasma EBV DNA is an accurate and reliable biomarker for NPC for WHO type 2 and 3 tumours even in non-endemic regions.

Context: Differentiating NSCLC as either adeno or squamous type and identification of Epidermal Growth Factor Receptor (EGFR) mutations is clinically relevant for lung cancer patients for selecting treatment. Thyroid transcription factor-1 (TTF-1) and p63 were demonstrated as useful markers for histologic typing of lung cancer. Mutation and overexpression of EGFR has been reported in a subset of non-small cell lung cancers. If these markers can be validated for the differential diagnosis of adenocarcinoma in a sputum sample itself, it will be highly beneficial for lung cancer patients. Aims: To evaluate whether immunocytochemical expression of TTF-1, p63, and EGFR proteins in sputum samples can be used for differential diagnosis of lung adenocarcinoma by comparing with that of the corresponding tissue samples. Settings and Design: Ninety sputum samples and matched tissue samples were used for the study. Subjects and Methods: Monolayered smears and cell blocks of sputum and the corresponding tissue samples were immunostained with the standard ABC method. The expression patterns of these markers were analyzed statistically and compared with clinic-pathological parameters. Statistical Analysis Used: Chi-square test and paired t-test. Results: The p63 protein had a positive expression in 73.9% of SCC whereas TTF1 had positive expression in 75.8% of ADC. The EGFR expression was positive in 27 cases of adenocarcinoma, 21 cases of SCC and 19 cases of NSCLC. Conclusions: Immunocytochemistry of the aforementioned antibodies in sputum samples can be used as supplementary evidence for the subtyping of NSCLC.

In time to event analysis, the risk for an event is usually estimated using Cox proportional hazards (CPH) model. But CPH model has the limitation of biased estimate due to unobserved hidden heterogeneity among the covariates, which can be tackled using frailty models. The best models were usually being identified using Akaike information criteria (AIC). Apart from AIC, the present study aimed to assess predictability of risk models using survival concordance measure. CPH model and frailty models were used to estimate the risk for breast cancer patient survival, and the frailty variable was assumed to follow gamma distribution. Schoenfeld global test was used to check the proportionality assumption. Survival concordance, AIC and simulation studies were used to identify the significance of frailty. From the univariate analysis it was observed that for the covariate age, the frailty has a significant role ( = 2.758, -value: 0.0004) and the corresponding hazard rate was 1.93 compared to that of 1.38 for CPH model (age > 50 vs. ≤ 40). Also the covariates radiotherapy and chemotherapy were found to be significant ( = 5.944, -value: <0.001 and = 16, -value: <0.001 respectively). Even though there were only minor differences in hazard rates, the concordance was higher for frailty than CPH model for all the covariates. Further the simulation study showed that the bias and root mean square error (RMSE) obtained for both the methods was almost the same and the concordance measures were higher for frailty model by 12–15%. We conclude that the frailty model is better compared to CPH model as it can account for unobserved random heterogeneity, and if the frailty coefficient doesn’t have an effect it gives exactly the same risk as that of CPH model and this has been established using survival concordance.