IADR Abstract Archives
Molecular Characteristics of High -Risk HPV Positive Oral Potentially Malignant Disorders
Objectives: High–risk HPV (HRHPV) 16/18 and their oncogenes can lead to oral carcinogenesis and malignant transformation of Oral Potentially Malignant Disorders (OPMDs) by promoting inhibition of apoptosis and dysregulation of cell-cycle. The objective was to compare the molecular characteristics ( BAX, Bcl-2, VEGFA, HIF-1a, PCNA, IL-6) between HRHPV positive and negative OPMDs using invasive tissue biopsy and non- invasive cytobrush sampling methods.
Methods: A prospective observational study where 101 subjects with clinical and histological diagnosis of OPMDs [33 Oral Submucous Fibrosis(OSMF), 34 Oral Leukoplakia(OL), 34 Oral Lichen Planus (OLP)] and 35 approximately age and sex matched healthy Controls (C) were recruited after ethical clearance and informed consent. History of current/past malignancy, HPV related malignancy in their spouses/partners, HPV vaccination and uncontrolled systemic disease were exclusion criteria. Fresh frozen tissue from incisional biopsy in OPMDs and Cytobrush samples from lesion surface/ normal mucosa in both OPMDs and C respectively were processed for DNA isolation and real time PCR for HPV genotyping and mRNA expression of BAX, Bcl-2, VEGFA, HIF-1a, PCNA, IL-6 using cDNA. Kruskal Wallis and Mann Whitney test was used for comparison between the groups at significance level of p<0.05%.
Results: HR HPV 16/18 was detected in 18.81% of OPMDs and none in C in tissue and cytobrush (p=0.002). The mRNA expression of Bcl-2, VEGFA were higher in tissue (p<0.001), Bcl-2, VEGFA, PCNA were higher in cytobrush (p<0.001) while BAX was lower (p<0.001) in both tissue and cytobrush in HR HPV positive OPMDs.
Conclusions: The mRNA expression of pro-oncogenic cytokines in HR HPV positive OPMDs are significantly different than HR HPV negative OPMDs and C and are at higher risk for malignant transformation. Cytobrush sampling is safe, reliable, non- invasive alternative to invasive biopsy in screening and surveillance for HR HPV infection and pro-oncogenic cytokines in OPMDs.
Methods: A prospective observational study where 101 subjects with clinical and histological diagnosis of OPMDs [33 Oral Submucous Fibrosis(OSMF), 34 Oral Leukoplakia(OL), 34 Oral Lichen Planus (OLP)] and 35 approximately age and sex matched healthy Controls (C) were recruited after ethical clearance and informed consent. History of current/past malignancy, HPV related malignancy in their spouses/partners, HPV vaccination and uncontrolled systemic disease were exclusion criteria. Fresh frozen tissue from incisional biopsy in OPMDs and Cytobrush samples from lesion surface/ normal mucosa in both OPMDs and C respectively were processed for DNA isolation and real time PCR for HPV genotyping and mRNA expression of BAX, Bcl-2, VEGFA, HIF-1a, PCNA, IL-6 using cDNA. Kruskal Wallis and Mann Whitney test was used for comparison between the groups at significance level of p<0.05%.
Results: HR HPV 16/18 was detected in 18.81% of OPMDs and none in C in tissue and cytobrush (p=0.002). The mRNA expression of Bcl-2, VEGFA were higher in tissue (p<0.001), Bcl-2, VEGFA, PCNA were higher in cytobrush (p<0.001) while BAX was lower (p<0.001) in both tissue and cytobrush in HR HPV positive OPMDs.
Conclusions: The mRNA expression of pro-oncogenic cytokines in HR HPV positive OPMDs are significantly different than HR HPV negative OPMDs and C and are at higher risk for malignant transformation. Cytobrush sampling is safe, reliable, non- invasive alternative to invasive biopsy in screening and surveillance for HR HPV infection and pro-oncogenic cytokines in OPMDs.