The invention relates to compounds and methods useful in detection and therapy of HPV-associated diseases. The invention is based on the elucidation of a mechanism by which replication of HPVs occurs in naturally infected tissues and cells. Moreover it is based on the identification of distinct epigenetic changes of the viral genome in infected cells that allows promotion of the affected cells to precancerous and cancerous cells. The invention therefore provides methods of diagnosing neoplasias and their precursor lesions as well as methods of preventing the development of malignancies or inhibiting tumor growth.