Persistent infection with high-risk human papillomavirus (HPV) genotypes is the leading cause of cervical cancer development. To this end several studies have focused on designing molecular assays for HPV genotyping, which are considered as the gold standard for the early diagnosis of HPV infection. Moreover, the tendency of HPV DNA to be integrated into the host chromosome is a determining event for cervical oncogenesis. Thus, the establishment of molecular techniques was promoted in order to investigate the physical status of the HPV DNA and the locus of viral insertion into the host chromosome. The molecular approaches that have been developed recently facilitate the collection of a wide spectrum of valuable information specific to each individual patient and therefore can significantly contribute to the establishment of a personalised prognosis, diagnosis and treatment of HPV-positive patients. The present review focuses on state of the art molecular assays for HPV detection and genotyping for intra-lesion analyses, it examines molecular approaches for the determination of HPV-DNA physical status and it discusses the criteria for selecting the most appropriate regions of viral DNA to be incorporated in HPV genotyping and in the determination of HPV-DNA physical status.