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Human Papilloma Virus (HPV) is a major risk factor for the development of oropharyngeal cancer. Automatic detection of HPV in digitized pathology tissues using in situ hybridisation (ISH) is a difficult task due to the variability and complexity of staining patterns as well as the presence of imaging and staining artefacts. This paper proposes an intelligent image analysis framework to determine HPV status in digitized samples of oropharyngeal cancer tissue micro-arrays (TMA). The proposed pipeline mixes handcrafted feature extraction wit