Survival of patients with cervical cancer in India - findings from 11 population based cancer registries under National Cancer Registry Programme.

Background: Cancer survival data from Population Based Cancer Registries (PBCR) reflect the average outcome of patients in the population, which is critical for cancer control efforts. Despite decreasing incidence rates, cervical cancer is the second most common female cancer in India, accounting for 10% of all female cancers. The objective of the study is to estimate the five-year survival of patients with cervical cancer diagnosed between 2012 and 2015 from the PBCRs in India. Methods: A single primary incidence of cervical cancer cases of 11 PBCRs (2012-2015) was followed till June 30, 2021 (n = 5591). Active follow-ups were conducted through hospital visits, telephone calls, home or field visits, and public databases. Five-year Observed Survival (OS) and Age Standardised Relative Survival (ASRS) was calculated. OS was measured by age and clinical extent of disease for cervical cancers. Findings: The five-year ASRS (95% CI) of cervical cancer was 51.7% (50.2%-53.3%). Ahmedabad urban (61.5%; 57.4%-65.4%) had a higher survival followed by Thiruvananthapuram (58.8%; 53.1%-64.3%) and Kollam (56.1%; 50.7%-61.3%). Tripura had the lowest overall survival rate (31.6%; 27.2%-36.1%). The five-year OS% for pooled PBCRs was 65.9%, 53.5%, and 18.0% for localised, regional, and distant metastasis, respectively. Interpretation: We observed a wide variation in cervical cancer survival within India. The findings of this study would help the policymakers to identify and address inequities in the health system. We re-emphasise the importance of awareness, early detection, and increase the improvement of the health care system. Funding: The National Cancer Registry Programme is funded through intra-mural funding by Indian Council of Medical Research, Department of Health Research, India, Ministry of Health & Family Welfare.

Breast cancer survival in India across 11 geographic areas under the National Cancer Registry Programme.

BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.

Oral cavity cancer incidence and survival trends: A population-based study.

INTRODUCTION: The present study aimed to calculate the burden of oral cavity cancer (OCC) including incidence, mortality rate, survival rate, and influence of predictive factors such as clinicopathological, demographic findings, and treatment modalities. MATERIALS AND METHODS: Data in this retrospective study were collected from India's population-based cancer registry (PBCR) from 2010 to 2016. A total of 1051 cases of OCC were noted. Incidence and mortality rates were calculated. The cumulative survival outcome was calculated using Kaplan-Meier (KM) method. Prognostic factors were estimated using the Cox proportional hazard regression model. RESULTS: The age-standardized incidence rates (ASR), and mortality rate (ASMR), of overall OCC cases were 10.1 and 8.4 per 100 thousand population, respectively. Five-year overall survival (OS) was 32.3%. Survival outcome was significantly associated with the given treatment (Chi-square value = 58.17, P = 0.0001) and anatomical site (Chi-square value = 26.70, P = 0.0001). 17.6% of cases in males were <39-year age group. The hazard ratio (HR) in the age group of >50 years was 2.065 (95% CI 1.34-3.18, P = 0.001). Combination therapy had an HR of 2.630 (95% CI 1.91-3.63, P value 0.000). Tonsillar carcinoma (C09) (95% CI 1.04-3.12) had 1.8 times more chances of death than lip carcinoma (C00). CONCLUSION: OCC cases are increasing in the younger population, and overall, cases show higher mortality rates with reduced survival outcomes. Prognostic factors such as age >50 years, single modality treatment, and alveolar and tonsillar malignancy are associated with poor survival. OCC robust screening by a trained health professional can improve early detection and increases awareness and lower mortality of the disease.

Financial impact of oral cancer treatment on the households in rural India.

Background: Oral cancer ranks second and accounts for over 20% of all cancers reported in India. Like management of all other cancers, oral cancers bring a heavy financial burden to their families. This study analyzes the financial burden on families during the management of oral cancer at Kasturba Hospital, Sewagram, a government-aided tertiary health care facility in central India. Methods: The hospital-based cross-sectional study was conducted in the cancer unit of a government-aided tertiary hospital of central India. A total of 100 patients with oral cancer being treated in the hospital were included in the study. Information regarding cost incurred on management of oral cancer was inquired from a close family member or a caregiver of the study subjects. Results: The out-of-pocket expenditure on treatment of oral cancer was approximately INR 100,000 (USD 1363). It has been found that 96% of families experienced catastrophic health expenditure as a result of treatment. Conclusion: Although India aims for universal health coverage, it is important to protect cancer patients from catastrophic health expenditure.

Choroid plexus papilloma in a mature cystic teratoma of ovary: A rare case report.

Mature cystic teratoma of the ovary is the most common type of germ cell tumor. It constitutes approximately 20% of all ovarian neoplasms. As a rare occurrence, however, several types of benign and malignant tumours developing secondarily in dermoid cysts have been reported. Those of central nervous origin are almost exclusively gliomas of astrocytic, ependymal or oligodendroglial lineage. Choroid plexus tumors are unusual intracranial tumors which comprised of only 0.4-0.6% of all brain tumors. These are neuroectodermal in origin and similar in structure to a normal choroid plexus in the form of multiple papillary fronds mounted on a well vascularized connective tissue stroma. The present case report highlights the presence of a choroid plexus tumor in a mature cystic teratoma of the ovary in a 27-year-old woman who came for safe confinement and cesarean section.

Angiomatoid Fibrous Histiocytoma in an Elderly Male: An Unusual Presentation of a Rare Case.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of low malignant potential often misdiagnosed clinically. It typically occurs in the superficial soft tissues of the extremities in children and young adults. It is characterized by recurrences and rarely metastases. Surgery remains the mainstay of management. Here, we present a rare case report of AFH in a 65-year-old male diagnosed using fine needle aspiration as spindle cell sarcoma. The patient underwent wide local excision. The patient is under follow-up. There is no evidence of metastases, and the patient is disease free three-years post-excision.

Ovarian cancer: A report from population-based cancer registry at central rural India.

INTRODUCTION: Ovarian neoplasms affect a huge part of the female population and, simultaneously, have the worst prognosis among all gynecological malignancies. In most of the population-based cancer registries (PBCR) in India, ovarian cancer is the third leading site of cancer among women, trailing behind cervix and breast cancer. MATERIALS AND METHODS: In the present study, we have summarized the number of new cases of ovarian malignancy and its profile observed in the PBCR in central India during 7 years. REPORTS: During a 7-year duration (2010-2016), 6,515 cancer patients were recorded at PBCR, and 228 cases were of ovarian malignancy. It was observed that most of the cases in this study were in 41-50 years of life. The age-standardized incidence rate of ovarian cancers in the present study was 4.61 per 100,000, and the crude incidence rate was 5.08 per 100,000. The crude mortality rate and age-standardized mortality rate of ovarian cancer were 2.3 and 2.02 per 100,000, respectively. Serous carcinoma was our study's most common histological subtype (43.75%), followed by mucinous carcinoma. CONCLUSION: A steady increase has been observed in the incidence of ovarian cancer in several registries. A significant goal in managing ovarian cancer is to develop an effective test to detect the disease at its earlier stages, resulting in reduced mortality.

Correlation of p53 expression with Clinical Presentation and Prognosis of Oral Squamous Cell Carcinoma Patients: A Pilot Study.

Mutations of p53 gene is one of the most common events in human cancers including oral squamous cell carcinoma (OSCC). However, its role in carcinogenesis and association with regard to prognosis is still under investigation and unclear. The aim was to study the expression of p53 in patients of OSCC and correlation with clinical presentation and prognosis. In this retrospective observational pilot study, we examined expression of p53 in 50 histologically diagnosed cases of OSCC and correlated it with initial clinical presentation and clinical events in follow up period. p53 expression was significantly negative (94%) in patients with history of only oral tobacco consumption while cases with additional history of smoking or alcohol were positive (p = 0.0001 and 0.011). On the other hand, aggressive course of the disease was found to be significant with p53 positivity in the form of lymph nodal extension (13 out of 17 cases) (p = 0.011) and recurrence (6 out of 10 cases) (p = 0.024). p53 was overexpressed (positive) in predisposing factors like smoking and alcohol but not in OSCC associated with chewing tobacco. p53 overexpression is also associated with advanced TNM stage. To the best of our knowledge, this is the first report where association of p53 overexpression and oral tobacco consumption associated OSCC was not observed and we recommend that carcinogenic events in chewing tobacco induced OSCC should be studied separately for its unique set of mutations.

Intraperitoneal dissemination of primary dedifferentiated liposarcoma of omentum simulating an ovarian cancer - A case report.

Dedifferentiated Liposarcoma (DDLPS) is a rare subtype of liposarcoma with a high preponderance of local recurrence and distant metastasis. The frequent site of DDLPS is the retroperitoneum, followed by the limbs and trunk. The primary omental DDLPS is very rare and only a few cases have been reported in the literature. Here we report a rare case of primary giant DDLPS of omentum with intraperitoneal metastasis in a 61year old woman. The present case report adds to our knowledge, that a case of intraperitoneal DDLPS can mimic ovarian cancer clinically and should be considered in the differential diagnosis of a pelvic mass in postmenopausal women.

Accuracy of high-risk HPV DNA PCR, p16(INK4a) immunohistochemistry or the combination of both to diagnose HPV-driven oropharyngeal cancer.

BACKGROUND: The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC. METHODS: The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16(INK4a) immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology. RESULTS: Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67. CONCLUSIONS: Single hrHPV DNA PCR and p16(INK4a) IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.

A protocol for good quality genomic DNA isolation from formalin-fixed paraffin-embedded tissues without using commercial kits.

BACKGROUND: DNA isolation from formalin-fixed paraffin-embedded (FFPE) tissues for molecular analysis has become a frequent procedure in cancer research. However, the yield or quality of the isolated DNA is often compromised, and commercial kits are used to overcome this to some extent. METHODS: We developed a new protocol (IARCp) to improve the quality and yield of DNA from FFPE tissues without using any commercial kit. To evaluate the IARCp's performance, we compared the quality and yield of DNA with two commercial kits, namely NucleoSpin® DNA FFPE XS (MN) and QIAamp DNA Micro (QG) isolation kit. RESULTS: Total DNA yield for QG ranged from 120.0 to 282.0 ng (mean 216.5 ng), for MN: 213.6-394.2 ng (mean 319.1 ng), and with IARCp the yield was much higher ranging from 775.5 to 1896.9 ng (mean 1517.8 ng). Moreover, IARCp has also performed well in qualitative assessments by spectrophotometer, fluorometer, and real-time PCR assay. CONCLUSION: Overall, IARCp represents a novel approach to DNA isolation from FFPE which results in good quality and significant amounts of DNA suitable for many downstream genome-wide and targeted molecular analyses. This protocol does not require the use of any commercial kits or phenol for isolating DNA from FFPE tissues, making it suitable to implement in low-resource settings such as low and middle-income countries.

Immunohistochemical Analysis Of Novel Biomarkers Cyclin D1, p53 And Ki67 In Endometrial Carcinoma: Clinicopathological Significance And Prognostic Value.

BACKGROUND: Endometrial carcinoma (EC) is the only gynecologic cancer with increasing incidence and mortality worldwide. This study aimed to determine association of cell proliferation marker CyclinD1, p53 and Ki67 with clinicopathological parameters and survival analysis in patients of EC. MATERIAL AND METHODS: One hundred twenty-four histological confirmed cases of EC treated at our institute were included in this study. The appropriate tissue blocks of cases which were retrieved from 2010 to 2015. The study period was from Jan 2018 to Jan 2020. Data pertaining to patient's clinical details, histopathological diagnosis, treatment and follow up was retrieved from Hospital information System. Immunohistochemical evaluation of Cyclin D1, p53 and Ki67 was done. Overall survival and Disease-free survival for each category were analyzed by the Kaplan-Meier method. RESULTS: Of the 124 cases of EC, 108(87.09%) cases were of type I and 16 (12.89%) cases of type II. Overall positive staining of cyclinD1, p53 and Ki67 were noted in 53.22%, 42.22% and 32.3% cases respectively. The clinicopathological parameters affecting disease-free survival were age (p=0.039) histological types (p=0.007), and FIGO stage (p< 0.001). Elevated Ki67 index and p53 overexpression was associated with type II morphology (p= 0.001). Whereas Cyclin D1 expression was associated with type I morphology and poorly differentiated tumor. CONCLUSION: Cyclin D1 positive staining, p53overexpression and an elevated Ki-67index all had an independent prognostic significance in endometrial cancer. This panel of biomarkers may help to differentiate tumor behavior, and necessity for more radical surgery and post- operative chemotherapy. Key words: Endometrial carcinoma; cyclin D1; p53; Ki67; Survival analysis.

Malignant Phyllodes Tumor with Heterologous Sarcomatous Differentiation: a Case Series and Review of Literature.

Malignant phyllodes tumor (MPT) with heterologous sarcomatous differentiation is extremely rare. We reviewed eleven cases of MPT with heterologous sarcomatous differentiation at our institute between 2009 and 2020. Demographic and clinical data were collected from patient records in hospital information system and population-based cancer registry. Each case reviewed retrospectively for the clinical features, prior treatment history, radiological imaging, histopathological and immunohistochemical details, disease stage, outcome and follow-up. On histopathology, four cases showed heterologous liposarcomatous differentiation, three cases showed fibrosarcomatous differentiation, two cases showed osteosarcomatous, and each case had angiosarcomatous and undifferentiated sarcomatous differentiation. Meticulous histopathological sampling along with a correct histopathological diagnosis and subtyping of the heterologous sarcomatous components is essential for planning treatment modality and prognostication of patients, although there are no clear-cut guidelines for surgical management and targeted therapy of these patients due its rarity and paucity of literature.

Intracranial Remote Metastasis from Adenoid Cystic Cancer of Parotid Gland: Case Report and Review of Literature.

Adenoid cystic carcinoma is rare, locally aggressive salivary gland tumor. It has indolent course, multiple local recurrences and delayed distant metastasis in lung, bone, liver and soft tissues which are detected up to a maximum of 5.5 years after local-regional resection of the primary tumor. Intracranial remote metastasis of ACCs is extremely rare, and very few cases have been reported in the literature. Here we report a rare case of intracranial remote metastasis of ACC of the parotid gland developed after 15 years of primary curative surgery, emphasizing long term follow up on these cases.

Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis.

Breast cancer stem cells (CSCs) are distinct CD44+-subpopulations that are involved in metastasis and chemoresistance. However, the underlying molecular mechanism of CD44 in breast CSCs-mediated tumorigenesis remains elusive. We observed high CD44 expression in advanced-stage clinical breast tumor samples. CD44 activation in breast CSCs sorted from various triple negative breast cancer (TNBC) cell lines induced proliferation, migration, invasion, mammosphere formation that were reversed in presence of inhibitor, 4-methyl umbelliferone or CD44 silencing. CD44 activation in breast CSCs induced Src, Akt, and nuclear translocation of pSTAT3. PCR arrays revealed differential expression of a metabolic gene, Lipoprotein lipase (LPL), and transcription factor, SNAI3. Differential transcriptional regulation of LPL by pSTAT3 and SNAI3 was confirmed by promoter-reporter and chromatin immunoprecipitation analysis. Orthotopic xenograft murine breast tumor model revealed high tumorigenicity of CD24-/CD44+-breast CSCs as compared with CD24+-breast cancer cells. Furthermore, stable breast CSCs-CD44 shRNA and/or intratumoral administration of Tetrahydrolipstatin (LPL inhibitor) abrogated tumor progression and neoangiogenesis. Thus, LPL serves as a potential target for an efficacious therapeutics against aggressive breast cancer.

HPV DNA genotyping, HPV E6*I mRNA detection, and p16INK4a/Ki-67 staining in Belgian head and neck cancer patient specimens, collected within the HPV-AHEAD study.

BACKGROUND: The main risk factors for head and neck cancer (HNC) are tobacco and alcohol use. However, an important fraction of oropharyngeal cancer (OPC) is caused by human papillomaviruses (HPV), a subgroup with increasing incidence in several western countries. METHODS: As part of the HPV-AHEAD study, we assessed the role of HPV infection in 772 archived tissue specimens of Belgian HNC patients: 455 laryngeal (LC), 106 oral cavity (OCC), 99 OPC, 76 hypopharyngeal (HC), and 36 unspecified parts of the head and neck. All specimens were tested for HPV DNA (21 genotypes); whereof all HPV DNA-positives, all HPV DNA-negative OPCs and a random subset of HPV DNA-negatives of the other HNC-sites were tested for the presence of type-specific HPV RNA and p16INK4a over-expression. RESULTS: The highest HPV DNA prevalence was observed in OPC (36.4 %), and was significantly lower (p < 0.001) in the other HNCs (OCC:7.5 %, LC:6.6 %). HPV16 was the most common HPV-genotype in all HNCs. Approximately 83.0 % of the HPV DNA-positive OPCs tested HPV RNA or p16-positive, compared to about 37.5 % and 44.0 % in OCC and LC, respectively. Estimation of the attributable fraction of an HPV infection in HNC was very similar for HPV RNA or p16 in addition to DNA-positivity; with 30 % for OPC, and 3 % for OCC and LC. CONCLUSION: Our study confirms the heterogeneity of HPV DNA prevalence across anatomical sites in HNC, with a predominance of HPV16 in all sites. The estimated proportion of HPV-driven HNC in Belgium, during the period 1980-2014, was 10 times higher in OPC compared to OCC and LC.

Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers.

Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δß) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. SIGNIFICANCE: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/10/2612/F1.large.jpg.

Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study.

Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000-2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.