Salivary DNA methylation markers for cancer of oral cavity.

PURPOSE: Aberrant DNA methylation plays a crucial role in oral carcinogenesis. Our previous study demonstrated hypermethylation of DAPK1, LRPPRC, RAB6C, and ZNF471 promoters in patients with tongue squamous cell carcinoma compared with normal samples. Methylation profiling using salivary DNA is considered a non-invasive alternative to tissue samples. Hence, the present study tested the DNA methylation status of these four promoters as indicators of oral cancer progression. METHODS: We performed the bisulfite-based targeted next-generation sequencing of four candidate genes in saliva and tissue DNA from normal, premalignant, and squamous cell carcinoma subjects. The clinicopathological association, diagnostic, and prognostic utility of aberrant DNA methylation were evaluated using the TCGA-HNSCC dataset. Using the Xgboost algorithm and logistic regression, CpG sites were prioritized, and Receiver Operating Characteristic was generated. By Log-rank test and Kaplan-Meier (KM) curves, an association between methylation and overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) were computed. RESULTS: We identified all four genes as significantly hypermethylated in premalignant and malignant samples compared with normal samples. The methylation levels were comparable between saliva and tissue samples with an r-value of 0.6297 to 0.8023 and 0.7823 to 0.9419 between premalignant tissue vs. saliva and OC vs. saliva, respectively. We identified an inverse correlation between DAPK1, LRPPRC, RAB6C, and ZNF471 promoter methylation with their expression. A classifier of 8 differentially methylated CpG sites belonging to DAPK1, RAB6C, and ZNF471 promoters was constructed, showing an AUC of 0.984 to differentiate tumors from normal samples. The differential methylation status of DAPK1, LRPPRC, and ZNF71 promoters was prognostically important. Abnormal expression of all four genes was associated with immune infiltration. CONCLUSIONS: Thus, methylation analysis of these candidate CpG sites from saliva can be helpful as a non-invasive tool for the clinical management of OC.

Targeted drug delivery in cervical cancer: Current perspectives.

Cervical cancer is preventable yet one of the most prevalent cancers among women around the globe. Though regular screening has resulted in the decline in incidence, the disease claims a high number of lives every year, especially in the developing countries. Owing to rather aggressive and non-specific nature of the conventional chemotherapeutics, there is a growing need for newer treatment modalities. The advent of nanotechnology has assisted in this through the use of nanocarriers for targeted drug delivery. A number of nanocarriers are continuously being developed and studied for their application in drug delivery. The present review summarises the different drug delivery approaches and nanocarriers that can be useful, their advantages and limitation.

Cervical cytology and associated factors among tribal women of Karnataka, India.

BACKGROUND: Reproductive well-being is a crucial element of women's health. Due to the asymptomatic nature of gynaecological morbidities, women rarely seek medical advice in the initial period leading to delayed diagnosis and poor prognosis of subsequent disease. The present study aimed to explore the cervical cytology and its associated risk factors among women from tribal communities of the southern part of coastal Karnataka, India. METHODS: Papanicolaou (Pap) smear test was performed among 1140 women from three tribal populations, to detect cervical lesions, infections and reactive changes. A semi-structured questionnaire was administered to collect data on socio-demographic and reproductive characteristics of the study population. RESULTS: The most predominant gynaecological complaint among the participants was severe lower back ache (77.6%), followed by white discharge per vagina (29.0%) and menstrual irregularities (25.9%). Of the 1140 women screened, 12.4% showed cervical microbial infections, 23.6% were reported to have reactive changes, and 0.2% had epithelial cell abnormalities in the cervix. Cervical microbial infections were found to be associated with younger age group, low socio-economic status and younger age at sexual debut. CONCLUSION: Most of the symptoms suggestive of gynaecological morbidities reported in this study are preventable or treatable. Strengthening ongoing cervical cancer screening programme and implementation of health education programmes among tribal population would be the right policy approach to prevent, detect and treat these symptoms at an early stage and to achieve acceptable health outcomes among tribal women.

Knowledge, Attitude and Practices Towards Cervical Cancer and its Screening Among Women from Tribal Population: a Community-Based Study from Southern India.

BACKGROUND: Cervical cancer continues to be a leading cancer among women in India. Despite availability of various screening techniques, majority of Indian women remain unscreened for cancer cervix. The increasing incidence could be attributed to the lack of awareness regarding cervical cancer screening and paucity of organized screening facilities in the country. This study assessed the knowledge, attitude and practices (KAP) towards cervical cancer screening among tribal women of coastal Karnataka, southern India. METHODS: A community-based cross-sectional study was conducted among 1140 women aged 20-65 years from three tribes. Information on their KAP towards cervical cancer screening was collected using a semi-structured questionnaire. RESULTS: Mean age of the participants was 39.8 ± 10.1 years. Although 82.9% of the participants reported to have heard of cervical cancer, 51% were aware that the disease could be prevented, and only 2.3% knew that it can be detected at an early stage. Over 75% of the participants did not have adequate knowledge regarding cervical cancer. However, majority of them (99.9%) had a favourable attitude towards cervical cancer screening. None of them had undergone cervical cancer screening prior to the study. The knowledge scores were significantly associated with age group, marital status, education level, socioeconomic status and tribal community of the participants (p < 0.05). CONCLUSION: Overall knowledge regarding cervical cancer among the surveyed women was poor, though they exhibited a positive attitude. This calls for a sustained health education and screening program to create awareness and improve the uptake of cervical cancer screening among these women.

Human papilloma and other DNA virus infections of the cervix: A population based comparative study among tribal and general population in India.

BACKGROUND: Despite being preventable, cervical cancer remains a major health concern among women. Persistent Human Papillomavirus (HPV) and other viral co-infections may influence cervical dysplasia. We determined and compared the prevalence and risk factors of cervical viral infections among the tribal and general population of southern coastal Karnataka, India. METHODS: A population-based cross-sectional survey was conducted among 1140 and 1100 women from tribal and general population, respectively. Cervical infections with HPV, Epstein-Barr Virus (EBV), Cytomegalovirus (CMV) and Herpes-Simplex Virus (HSV) were examined using polymerase chain reactions (PCR) and DNA sequencing. RESULTS: HPV prevalence was higher among tribal women (40.6%) than general population (14.3%) while the prevalence of EBV (55.1%) and CMV (49.4%) were lower among tribal women than general population (74.3% and 77.5%, respectively). HSV infection was observed in tribal women only (1.8%). Among HR-HPV strains, HPV-18 was predominant among tribal population (28.3%) while, HPV-16 was predominant among the general population (9.1%). Infections were associated with age, educational status, unemployment and personal hygiene of tribal women. Phylogenetic analysis revealed that HPV-16 variants of tribal participants were closely related to non-European sublineages indicating greater risk of HPV persistence and carcinogenesis. CONCLUSION: The study provides a comparative estimate for DNA virus infections of the cervix among women from general as well as tribal population in this region and also reveals a different type-specific pattern of viral infection. Further research is required to delineate the role of specific interactions between multiple virus infections and their role in carcinogenesis.

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer.

Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events. Recent studies have also mapped these epigenetic modification and pathways leading to carcinogenesis. Discovery of drugs that target proteins/enzymes in the epigenetic pathways may provide better therapeutic opportunities, and identification of such modulators for DNA methylation, histone modifications, and expression of noncoding RNAs for several cancer types is underway. In this review, we provide a detailed description of recent developments in the field of epigenetics and its impact on personalized medicine to manage cervical cancer.

Prevalence of human papillomavirus types and phylogenetic analysis of HPV-16 L1 variants from Southern India.

BACKGROUND: The human papillomavirus (HPV) and its variants show wide geographical distribution and have been reported to cause cervical lesions. With cervical neoplasia as the leading cancer in Indian women, the aim of the present study was to evaluate the multiple infection HPV type distribution and variant genotypes in cervical samples from the coastal Karnataka region, India. MATERIALS AND METHODS: A total of 212 samples were screened by nested polymerase chain reaction using PGMY9/11 and GP5+/6+ primers. HPV positive samples were sequenced to identify the types and a phylogenetic tree was constructed using the neighbor-joining method. RESULTS: Sequence analysis identified a total of 14 HPV types distributed in 20%, 73.3% and 82.5% of non-malignant, pre-malignant [low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in cancer samples was HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35, 1.4% and HPV 45, 1.4%. Multiple infections were observed in 11.8% of tumor samples with HPV 16 contributing to 62.5% of cases. In non-malignant samples, 20% of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58, 5.8% and very low incidence of multiple infections. Comparative phylogenetic analysis of HPV variants identified 9 HPV sequences as new papillomavirus species, predominantly classified as European lineage type. CONCLUSIONS: The findings for HPV infections associated with progression of cervical cancer in coastal Karnataka region and HPV variant analysis provide baseline data for prevention and HPV vaccination programs.