No abstract

Background: Cervical cancer is a major health hazard to Indian women. Human papillomavirus (HPV) infection is an established risk factor for cervical carcinogenesis. However, understanding the cervical cancer biology beyond HPV infection is very crucial to predict aggressive behavior, prognosis, treatment response and survival. In the present study, we explored the role of vascular endothelial growth factor A (VEGFA) isoforms, VEGFC and VEGFD in cervical cancer progression and its association with HPV 16 and 18 infections. Material and Methods: A total of 110 cervical cancer tissues and 50 normal cervical tissues were collected for the study. Reverse transcription-polymerase chain reaction was employed to analyze tissue VEGFA isoforms, VEGFC and VEGFD expression. Results: VEGF165 was significantly higher, whereas VEGFC and VEGFD were significantly lower in malignant cervical carcinoma tissues as compared to normal cervix tissues. Expression levels of VEGF121 and VEGFC were significantly associated with type of tumor growth while VEGF165 was significantly associated with lymph node metastasis. VEGF165 transcript levels were significantly higher in patients with squamous cell carcinoma (SCC) and developed recurrence. Most strikingly, higher VEGF165 expression was significantly associated with worst disease-free survival (DFS) specifically in patients with SCC. Conclusion: Association of VEGF165 with lymph node metastasis, disease recurrence and worst DFS indicated that VEGF165 is an important prognostic factor in cervical carcinogenesis.

OBJECTIVES: Cancer is a multi-factorial disease, with various intrinsic and environmental factors contributing to its occurrence. Human papillomavirus (HPV) has been associated with the occurrence of many cancers. India severely suffers from 3 HPV-associated cancers (cervical cancer, oral cancer, and oropharyngeal cancer). Hence, the present study aimed to evaluate the HPV burden in these 3 cancers among patients from the western region of India.METHODS: DNA was isolated from samples from 400 cervical cancer, 127 oral cancer, and 75 oropharyngeal cancer patients. Polymerase chain reaction was performed using degenerate primers for HPV infection.RESULTS: Overall, HPV infection was observed in 87% of cervical cancer cases, 12.5% of oral cancer cases, and 26.7% of oropharyngeal cancer cases when analyzed with a cumulative detection method using the MY 09/11, GP 5+/6+, and CP I/II primer sets.CONCLUSIONS: A significant prevalence of HPV infection was detected in all 3 cancers using the degenerate primer sets. This finding implies that testing for HPV infection using multiple primer sets is crucial for determining its actual prevalence in various malignancies.

Background: Cervical cancer is one of the leading malignancies in women of India with high mortality rate and no available targeted therapy. This is due to dearth in understanding of underlying mechanisms regulating cervical carcinogenesis and distinguished behavioral pattern of HPV-associated carcinomas. This study aims to understand association of HPV infection and cervical cancer with aberrant glycosylation, an enabling factor for other hallmarks of cancer. Materials and Methods: DNA and RNA were isolated from biopsy samples of 92 cervical cancer patients. HPV 16 and 18 infection was detected by endpoint Type-Specific PCR. RNA samples were processed for expression analysis of HPV 16-E6, HPV 16-E7 and HPV 16-E2 oncogenes. Analysis of the expression of glycosylation transcripts were performed using qPCR. Results: Correlation of HPV infection with transcript levels of ST3GAL3, ST6GAL1, FUT5 and FUT8 was observed. In HPV 16 and 18 positive patients, the transcript levels of ST3GAL3, ST6GAL1 and FUT5 were higher while FUT8 transcripts levels showed down-regulation. Conclusion: This data depicts hyper-glycosylation patterns associated with HPV infection. HPV-associated cancers showed down regulation of core fucosylation and up-regulation of ST3GAL3, ST6GAL1 and FUT5. The behavioral pattern for HPV-associated cancer could be due to its differential association with altered glycosylation.

Introduction: Oral cancer is cause mainly due to habits of tobacco consumption and it is a major health hazard across the world. The death rate due to the disease is also very high. However, the association of tobacco exposure with stage of the disease and treatment outcome is not reported. Therefore, we assessed correlation between levels of tobacco exposure with the disease status and treatment outcome in oral cancer patients. Materials and Methods: Urine samples were collected from enrolled pre-therapeutic oral cancer patients (N=96), healthy individuals with tobacco habits (N=19) and healthy individuals without tobacco habits (N=14). Urinary nicotine and cotinine levels were analyzed as indicators of tobacco exposure by HPLC methods. Data was statistically analyzed using the SPSS statistics version 20.0. Results: Present study revealed that tobacco exposure levels were significantly higher in oral cancer patients and healthy individuals with tobacco habits as compared to healthy individuals without tobacco habits. Receiver Operating Characteristics (ROC) curve analysis revealed that tobacco exposure levels have a good discriminatory efficacy between healthy individuals without habit of tobacco and oral cancer patients as well as between healthy individuals without habit of tobacco and healthy individuals with habits of tobacco. Kaplan Meier survival curve analysis also revealed that patients who were having higher tobacco exposure levels at the time of diagnosis showed worse survival than patients who were having lower tobacco exposure levels. Conclusion: Tobacco exposure levels could be a simple, non-invasive and cost effective prognostic biomarker for management of oral cancer. Keywords: Tobacco exposure, Cotinine, Nicotine, HPLC, ELISA, Oral Cancer, Urinary biomarker.