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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.

Treatment options for early-stage oropharyngeal squamous cell carcinomas (OPSCC) (Stages I and II) include definitive radiation or surgery. This retrospective study aims to evaluate the outcomes of early-stage (Stages I and II) OPSCC treated with radical radiation. The data of patients with early-stage OPSCC (T1/T2N0) treated with definitive radiation at the Regional Cancer Center, Trivandrum, Kerala, India, from 1st January 2015 to 31st December 2020 were retrieved from medical records. A structured proforma was used to gather clinical and therapeutic details of the patients. The primary objective was to assess loco-regional control and patterns of relapse. Secondary objectives were to assess overall survival (OS), disease-free survival (DFS) and prognostic factors affecting the treatment outcomes. DFS and OS were generated using Kaplan-Meier Curves. The prognostic factors affecting the outcomes were analysed using the Cox-proportional hazards regression model. One hundred and twelve patients with early-stage oropharyngeal cancers who received definitive radiation were included in the study. The majority (91.97%) were males and 90% (101) of the patients had tobacco and alcohol-related habits. Twenty-six (23.3%) among the 112 patients had stage I disease and 86 (76.7%) had stage II disease. The median age group of the study population was 62 years. The most commonly affected primary site was the tonsil ( = 38, 33.9%), followed by the soft palate ( = 34, 30.3%) and followed by the base of the tongue ( = 23, 20.5%). The majority of the patients (80.4% ( = 90)) received a radiotherapy (RT) dose of 60 Gy in 26 fractions at 2.3 Gy per fraction over 5.5 weeks. One hundred nine (97.3%) patients attained remission at 12 weeks following radiation. Three patients had residual disease and none of them underwent salvage surgery. Twenty-one percent ( = 24) of patients had relapsed and the median time to relapse was 20 months. Among the relapses, 7 (29%) underwent salvage surgery and others were given palliative treatment. The most frequent site of relapse was the primary site followed by regional nodes. At a median follow-up of 63 months, the 4-year DFS was 67.9% and OS was 75%. Stage-wise 4-year DFS and OS for stages 1 and II were 68.1% and 64.1%, 78.9% and 73.8%, respectively. The locoregional relapse-free survival at 4 years was 75.2%. Five patients developed a second malignancy and the lung was the most common site. In univariate analysis, age was the only significant prognostic factor that affected the treatment outcomes. The survival outcomes of the patients treated with definitive RT are comparable with the published literature. However, the salvage rates were very poor.

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.

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.

Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant neoplasm arising from the neural crest cells of the olfactory epithelium. The optimum treatment for this rare disease is still unclear. Most of the available literature on this rare head and neck tumour is limited to small retrospective series and single institutional reports. We conducted a retrospective study to investigate the clinical profile, treatment outcomes and prognostic factors of patients with ENB treated at a tertiary cancer centre in south India. Patients with a histopathological diagnosis of ENB treated from 2000 to 2019 were included. Patient demographics, tumour characteristics, stage, treatment details and outcome data were identified from medical records. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and the log-rank test was used for comparison. The prognostic factors were identified using Cox regression analysis. Forty-two patients underwent treatment for ENB from 2000 to 2019. Twenty-six patients underwent surgery. Twelve patients received radical radiotherapy (RT) while 24 patients underwent adjuvant radiation. After a median follow-up of 71 months, the estimated OS and DFS at 4 years were 64.4% and 54%, respectively. The estimated 4-year OS for modified Kadish A, B, C and D stages was 75.0%, 90.9%, 56.4% and 0%, respectively. Modified Kadish stage, nodal involvement, orbital invasion, intracranial extension, surgery, RT treatment and use of chemotherapy were significant predictors of OS and DFS in univariate Cox regression analysis. Orbital invasion and RT treatment were significant predictors of DFS in the multivariate analysis as well. However, only RT treatment came out to be a significant predictor for OS in multivariate Cox regression analysis. Surgery is the mainstay of treatment. Adjuvant RT may improve local control and survival in advanced cases. Advanced modified Kadish stage, lymph node involvement and orbital invasion are associated with poor outcomes.

Oral and lip cancer is the most common type of cancer among males in India. Early stage tumours of the lip (stages I and II) are treated with single modality treatment, using either radiotherapy [external beam radiotherapy (EBRT) or brachytherapy] or surgery. Locally advanced tumours (stages III and IVa) are treated with surgery followed by adjuvant treatment. The aim of the present study was to retrospectively evaluate the clinical profile and treatment outcomes of patients with squamous cell carcinoma of the lip who were treated with radical intent at the Regional Cancer Centre (Thiruvananthapuram, India). For this purpose, a total of 120 patients treated with radical radiotherapy (brachytherapy or EBRT) or surgery with or without adjuvant treatment between January 2010 and December 2016 were eligible for the analysis. Kaplan-Meier analysis was used to generate the survival outcomes. Univariate and multivariate analyses were performed to determine the impact of various patient- and tumour-related factors and treatment modality on outcomes. At a median follow-up time of 67.6 months, the disease-free survival (DFS) and overall survival (OS) rates at 4 years for the entire cohort were 69.1 and 86.7%, respectively. The 4-year OS rates for patients with stage I, II, III and IV disease were 88.9, 95.2, 86.8 and 75.3%, respectively, and the DFS rates were 83.6, 69.5, 78.8 and 42.9%, respectively. Primary tumour (P=0.025), nodal (P=0.005) and composite clinical (P=0.006) stage were found to be significant factors affecting DFS rates in the univariate analysis. However, only the nodal stage (P=0.005) was found to be a significant factor affecting DFS rates in the multivariate analysis. On the whole, the present study demonstrates that the outcomes of patients with lip carcinoma are favourable when treated at the early stages, and the results from this series are in line with those already published.

Chemoradiation is the standard treatment for patients with locally advanced laryngeal carcinoma with intact cartilage and functional larynx. The aim of this retrospective study was to assess overall survival (OS) and disease-free survival (DFS) of patients with locally advanced (stage III and stage IV) squamous cell carcinoma of the larynx who have been treated with definitive radical radiotherapy (RT) with or without chemotherapy in a tertiary cancer center in India between January 1, 2006 and December 31, 2015. Data were collected using structured proforma. The patients were treated with RT alone, induction chemotherapy (IC) followed by RT, concurrent chemoradiation therapy (CCRT) or IC followed by CCRT. Response assessment was conducted at 3-4 months post-treatment. Patient-, tumor- and treatment-related factors were documented and were associated with DFS and OS. Survival curves were generated using the Kaplan-Meier method and the statistical significance of survival curves was assessed using the log-rank test. Prognostic factors were assessed using the Cox proportional hazards regression model. A total of 630 patients were included in the present study. The most common age group at presentation was 50-70 years (n=477; 75.7%) and 95.4% (n=601) patients were male. The most common stage at presentation was stage III (n=367, 58.1%). The median follow-up period for the entire group of was 59 months (range, 2-175 months). A complete response after treatment was seen in 549 patients (87.1%). Salvage surgery was performed for 11 patients with residual disease. A total of 134 patients (21.3%) had developed locoregional and distant relapses, and salvage surgery was performed for 31 out of 102 patients with locoregional relapse. The 5-year OS was 48.7% and the 5-year DFS was 45.7%. The stage-wise OS rates were 58.9, 34.9 and 30.4% (P=0.001) and the stage-wise DFS rates were 56.3, 32.0 and 21.7 (P=0.001) for stage III, IVa and IVb, respectively. Results from the present study demonstrated the feasibility of delivery of chemoradiation protocols with good results in a developing country.

Objective. To retrospectively evaluate the clinical outcome of carcinoma nasopharynx patients treated with the IMRT technique. Methods. Eighty-one nasopharyngeal carcinoma patients who were treated with IMRT with or without chemotherapy between the period January 2011 and December 2014 at a comprehensive tertiary cancer center, Kerala, India, were included in the study. The mean age was 43 years (range 13–77 years), and majority of the patients were males (67.9%). The stagewise distribution of disease at presentation was 2 (2.5%) in stage I, 19 in stage II (23.5%), 31 (38.3%) in stage III, and 29 (35.8%) in stage IV. All patients were treated using simultaneous integrated boost (SIB) schedule using IMRT with 6 MV photon to a dose of 66 Gy in 30 fractions, 2.2 Gy per fraction prescribed to high-risk PTV; 60 Gy in 30 fractions, 2 Gy per fraction to intermediate risk PTV; and 54 Gy in 30 fractions, 1.8 Gy per fraction to low-risk PTV. Concurrent chemotherapy with cisplatin was offered to patients with stage II and above disease. Neoadjuvant chemotherapy with cisplatin and 5FU was given to patients with initially advanced disease (T3, T4, N2, and N3). Survival estimates were generated using the Kaplan–Meier method. The univariate analysis was performed using log-rank tests. Results. The 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.5%, 87%, 61.6%, and 62.5%, respectively. The 5-year OS was 100% for stage I (n = 2), 67% for stage II (n = 19), 70.4% for stage III (n = 31), and 68.1% for stage IV (n = 29). The DFS at 5 years was 100% for stage I, 61.1% for stage II, 56.2% for stage III, and 84.8% for stage IV disease. The univariate analysis showed that age, nodal stage, and use of induction chemotherapy showed an improved trend towards OS, though the results were not statistically significant. The predominant pattern of failure in the present study was distant metastasis. Most patients who developed distant metastasis in our study had either an advanced T stage or N3 disease at presentation. Conclusion. The present study shows our initial experience with IMRT for nasopharyngeal carcinoma. The compliance to RT was good in this study. The 5-year LRC and OS rate of nasopharyngeal carcinoma patients treated with IMRT were 87.5% and 62.5%. Distant metastasis was the main pattern of failure.

Sinonasal small cell neuroendocrine carcinoma is a rare tumour in the head and neck region. Patients become symptomatic as the disease progresses to advanced stages. They are at risk for recurrence and distant metastasis following treatment. Early diagnosis and treatment have shown to improve the disease prognosis. This is a retrospective analysis of sinonasal small cell neuroendocrine carcinomas that underwent treatment based on institutional protocol. Data was collected from medical records of the patients and analyzed using descriptive statistics. Cell morphology on electron microscopy and immunohistochemistry played a significant role in differentiating small cell neuroendocrine carcinoma from other neuroendocrine tumours. 75% of cases presented in an advanced stage of malignancy. None of the patients had distant metastasis at initial presentation. Equal proportion of cases underwent surgery followed by adjuvant radiation (33.3%) and concurrent chemoradiation (33.3%). 25% of patients had recurrence of disease. The 2-year overall survival rate was 78.8%. Disease-free survival for cases that underwent surgery followed by radiation was higher than that of chemoradiation or radiation alone arms. There has been an improvement in treatment outcomes of sinonasal small cell neuroendocrine carcinoma which is best explained by paradigm shift in multimodality management towards surgery followed by adjuvant treatment.