Human papillomavirus genome associated correlates of disease progression and treatment response for cervical neoplasms and cancer

Human papilloma viruses of high carcinogenic risk (hrHPV) cause >90% of cervical cancer (CC). Latvia introduced HPV vaccination in 2010, but still registers 32.5 CC cases per 100000 population indicating insufficiency of current preventive efforts and requesting in-depth update of determinants of HPV pathogenesis. Project partners are Riga Stradins University and Paul Stradins University Hospital. We aim to genotype hrHPVs in healthy and diseased cervix and determine prevalent genotypes; characterize evolution of dominant strains, epitopic drift and host DNA damage due to HPV integration. Study will include women with squamous intraepithelial lesions and carcinomas and matching controls (40 each). The first will be followed every six month, and controls yearly. Cervical smears and biopsies will be collected and assessed by liquid cytometry, immunohistochemistry; hrHPVs will be genotyped and viral load determined. Genotype drift will be evaluated by comparing these data to hrRHPVs in matching samples collected before 2015. HPV will be sequenced to assess epitopic drift in sequential samples. HPV-human DNA chimeras resulting from HPV integration will be quantified. In vitro experiments will assess the effect of typical HPV DNA inserts on carcinogenicity of expressing epithelial cells. Epitopic drift and degree of DNA damage will be validated as early markers of malignization to personalize CC therapy. Results will be published in 6 papers in peer-reviewed journals ranked Q1-Q2.