Human Papillomavirus Variants: Implications for Natural History Studies and Vaccine Development Efforts

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Abstract
Experimental and epidemiologic data have established a causal link between infection with human papillomaviruses (HPVs) and all grades of cervical intraepithelial neoplasia (CIN)1 and invasive cervical cancer (1). While about 30 types of HPV are known to infect the genital tract, studies have shown that not all HPV types are created equal. Some types (most notably HPV types 16, 18, 31, 33, and 45) have been shown in epidemiologic studies to be more strongly associated with CIN 2-3 and cancer than others (most notably, HPV types 6 and 11, which cause mainly exophytic warts). Experimental evidence supports these observations, having shown that the HPVE6- and E7- transforming proteins from high-risk HPV types such as HPV16 have a higher transforming ability than those from low-risk HPV types such as HPV-6 and 11. In this issue of the Journal, Xi et al. (2) present evidence that minor variations within HPV types2 might also affect the magnitude of association with disease risk. Their results support those from previous small studies suggesting an association between HPV variants and persistence of infection or development of CIN2-3 and cancer (3,4). In their report of 19 cases of CIN2-3 arising from a group of 123 women followed longitudinally, Xi et al. suggest that infection with variant forms of HPV16 might be more strongly associated with the risk of developing CIN2-3 than infection with the prototype European HPV16 virus. This finding, if confirmed in larger studies, might influence both our understanding of the natural history of HPV-related anogenital diseases and our efforts to develop HPV vaccines. Each of these will be discussed in turn.