Abstract
We investigated the relationship between high-grade cervical disease (cervical intraepithelial neoplasia [CIN] 2, CIN3 or adenocarcinoma in situ) and persistent infection with HPV16 and/or HPV18 (HPV16/18) among 3970 women who received placebo in 3 clinical trials of a quadrivalent HPV vaccine. Statistical analysis (odds ratios, sensitivity, specificity, negative and positive predictive values, negative and positive likelihood ratios) showed that patients with a persistent infection with HPV16/18 had a much greater risk of HPV16/18-related high-grade cervical disease. Furthermore, subjects without a persistent infection with HPV16/18 were unlikely to have HPV16/18-related high-grade cervical disease. These results suggest that persistent infection with HPV16/18 meets the criteria for a surrogate endpoint for HPV16/18-related high-grade cervical disease and may be used as such in future clinical studies with prophylactic HPV vaccines and in natural history studies.