As HPV cannot be grown in cell cultures, clinical, cytological, and histologi-cal methods have traditionally been used to provide indirect evidence of HPV infection by demonstration of cellular dysplasia, which is one of the results of HPV infection. Colposcopic examination by visual inspection to detect abnormalities in the exterior parts of the genital tract is convenient and easily done at the bedside. However, this method is very insensitive, and hidden lesions in the cervix often remain undetected (Feng and Kiviat, 2003). Microscopic examination of exfoliated cell samples (Pap smears) or tissue biopsy specimens have long been used in cytological and histological methods for revealing HPV infections. Changes in HPV-infected cells can be rather subtle and there are nonspecific manifestations, such as koilocytosis or dyskeratosis of the squamous cells. These changes, however, are not always clearly presented and detectable by microscopy (Hippelainen et al., 1994). Poor intra- and interlaboratory reproducibility of the cytologic diagnosis of HPV infection has also been reported (Kiviat et al., 1992). On the other hand, serological assay based on serum antibodies mainly against the L1, L2, E6, and E7 HPV proteins, such as Western blot assay and enzyme-linked immunosorbent assays (ELSA), has been devised for detection of HPV infection. This approach has limited capability for HPV detection due mainly to difficulties associated with the large number of HPV types, cross-reactions between HPV, the diversity of clinical lesions, as well as target sites for infection (Coursaget, 2003). Advent of various virus-like particles (VLP) has enabled the use of these as valuable reagents for development of more sensitive and specific assays (Studentsov et al., 2003). As there is virtually no oncogenic viral genome present and that high titers of neutralizing antibodies appeared to be generated, these VLPs have also been used for development of prophylactic vaccine (Roden et al., 1996).
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