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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 HPVE6and E7transforming 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 types 2

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