Moderator of 4 Sessions
Presenter of 5 Presentations
CHAIR INTRODUCTION
LOCAL VIEW: ACCELERATING CERVICAL CANCER CONTROL IN JAPAN
CUTANEOUS HPV INFECTION
HPV E6 IS AN EVOLUTIONARILY CONSERVED BASAL EPITHELIAL HOMEOSTASIS REGULATOR, THAT FACILITATES VIRAL PERSISTENCE AND CAN BE TARGETED FOR DISEASE CLEARANCE
Abstract
Introduction
The evolution of PV has been the result of the coevolution of and adaptation to the specific epithelial niches where each PV colonises, resulting in their remarkable species and tissue specificity as well as unique pathogenicity. HPVs also share a general life cycle strategy, in which they establish a persistent reservoir of infection in the basal layer of stratified epithelium, for persistent infection as well as lesion formation. During persistent infection, E6 but not E7 viral protein is thought to play a major role in maintaining and expanding infected cells in the basal layers as a regulator of homeostasis.
Methods
Here, we describe a simple in vitro 2D/3D model system for studying basal epithelium homeostasis in the context of cell growth, contact inhibition, as well as the transition of cells from the basal to second layers (delamination/commitment of differentiation) independently.
Results
Taking HPV16 E6 as an example, which is most frequently causative of HPV-related cancers, we show how HPV16 E6 modulates basal epithelium homeostasis in those aspects via the degradation of p53, and PDZ-proteins, and contributes to lesion formation and maintenance overall. Also, other HPVs' E6s (α-HPV11/16/27, β-HPV8, γ-HPV65 and μ-HPV1) from different genera show similar phenotypes in different ways. Finally, we show that the model system could serve as a high-throughput screening system for the identification of small molecules which can inhibit E6's function in modulating basal epithelium homeostasis and therefore be potential candidates for anti-HPV reagents.
Conclusions
HPV E6 is an evolutionarily conserved basal epithelial homeostasis regulator, that contributes to viral persistence and can be targeted for disease clearance by small molecules which inhibit HPV E6 function.
CERVICAL CELL LIFT - A NOVEL METHOD FOR THE SPATIAL MAPPING BIOLOGICAL MARKERS AND GRADING OF HPV-INFECTED CERVICAL LESIONS
Abstract
Introduction
The persistent infection of high-risk HPV in the cervical transformation zone is the cause of cervical cancer. The majority of sexually active people become infected with high-risk HPV at some point in their life, however, only a small proportion of infected females develop cancer. In general, after the initial infection, HPV develops a temporal productive lesion and then the infection is controlled by the host immune system, leading to the latent persistent infection. In later life, the infection may be re-activated, develop into a pre-cancerous lesion, and in rare cases, progress to malignant cancer. The aim of cervical screening is to identify HPV-associated lesions that may progress to cancer in order to allow treatment.
Methods
Infected lesions can be categorised from productive low-grade lesions to non-productive high-grade lesions. These lesions are characterised based on the regulation/expression of viral oncogenes, and their morphological phenotype which provides insight into the different probabilities of cancer progression. The phenotypes (the biological markers) include the surrogate molecular markers of viral oncogene expression (MCM, Ki67, and p16) and the viral productive life cycle (E4) as well as cellular morphologies.
Results
We showed a new method to lift the surface cells of the cervix (Cervical cell lift, CCL) and generate a spatial map of the biological markers there. We have successfully located and characterised the infected lesion on the CCL. Compared to the normal cytology, the major advantage of the CCL is the preservation of native cell topology, and by preserving this spatial information, the lesions can be visualised in their entirety. The CLL detected CIN2+ lesion with 80% of sensitivity.
Conclusions
The CCL potentially can replace the current triage test (cytology) of cervical screening by providing the location and the grade (CIN1-CIN3) of the infected lesion without biopsy and histopathological assessment.