Current problems and recent advances in the molecular diagnosis of genital human papillomavirus infections

It was proven in the early 1980s that cervical cancer (CC) biopsy specimens and CC cell lines contain human papillomavirus (HPV) DNA sequences. In subsequent years, researchers discovered that the E6 and E7 genes of HPV are expressed in CC tissues and these oncoproteins interact with cellular proteins, including pRb and p53. Establishment of the relationship between HPV infections and CC led to increasing interest on this topic. Comprehensive epidemiological studies determined that specific types of HPV are major risk factors for CC. These HPV types, called high-risk or oncogenic types, are associated with other anogenital cancers and a subset of head and neck cancers. A number of commercial and in-house diagnostic techniques, each of which has a different approach and methodology, have been developed to diagnose HPV infections. HPV testing based on the detection of viral DNA has become an important part of CC screening programs. These screening-typing methods and combined approaches, which are used to diagnose and follow-up (management) HPV infections, have advantages and disadvantages. The choice of method is complicated by several factors and challenges that arise owing to the nature of the virus and the assay methodology. For example, a number of different HPV types can cause genital infections, multiple sequence variations are often observed even in the same HPV genotype, the detection sensitivity of the available methods is variable depending on the HPV genotypes and the viral DNA copy number in the samples examined. The capability for the detection of multiple infections and the ability to perform genotyping differ between the methods. The aim of this review is to summarize the methods used for the diagnosis and follow-up of HPV infections, and to share the current informations that may be helpfull for the choice of appropriate method. For this purpose, molecular-based HPV tests that were used in the past and their development processes were described briefly, then currently accepted and widely used methods for diagnosis, screening, and typing were discussed in detail, along with their advantages and disadvantages.