Relationships between 80 human papillomavirus genotypes and different grades of cervical intraepithelial neoplasia: association and causality.

To clarify the causal relationship between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), we analyzed 386 unfixed biopsy specimens by blot hybridization at Tm -40 degrees C, targeting 38 skin and 42 genital HPVs. By the recognition of PstI, BanI, and MspI cleavage patterns, single genital, but no skin's HPVs were identified with more than 10 copies per cell in 354 CIN (88 CIN I, 94 CIN II, and 172 CIN III). HPVs 40, 42, 43, 54, 62, or 71 was found in 10 CIN I, while HPVs 18, 30, 39, 51, 56, 59, 66, 68, 69, or 82 was found in 35 CIN I, 20 CIN II, or 8 CIN III. On the other hand, HPVs 16, 31, 33, 35, 52, 58, or 67 was identified in 43 CIN I, 74 CIN II, or 164 CIN III. The results are strongly indicative that most genital HPVs have potency to induce CIN I; however, HPV 16 and its closely related types are able to efficiently induce CIN III. We discuss the definition of causal HPV for CIN with regard to viral prevalence and viral load.