Persistent infection with human papillomavirus 16 or 18 is strongly linked with high-grade cervical disease

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.

Keywords:

• cervical intraepithelial neoplasia
• cervical cancer
• statistics
• HPV
• Prentice criteria
• surrogate endpoint

Abbreviations

AIS	=	adenocarcinoma in situ
CIN	=	cervical intraepithelial neoplasia

Funding

This study was supported by Merck & Co., Inc., Whitehouse Station, NJ.

Disclosure of potential conflicts of interest

D. Radley is a former employee of Merck & Co., Inc., Whitehouse Station, NJ, holds stock and/or stock options, and is now at Pfizer. A. Saah is an employee of Merck & Co., Inc., Whitehouse Station, NJ, and holds stock and/or stock options. M. Stanley received speaker fees from Merck Sharp & Dohme, MSD, and was a consultant for Sanofi Pasteur MSD and GlaxoSmithKline Biologicals.

Acknowledgments

All authors were involved in the collection, analysis, or interpretation of the data; revision of the manuscript; and the decision to submit the manuscript for publication. The assistance of Frank Dutko (Merck & Co., Inc.) in writing the manuscript and the technical assistance of Karyn Davis (Merck & Co., Inc.), Scott Vuocolo (Merck & Co., Inc.) and Sheila Erespe (Merck & Co., Inc.) are very much appreciated. All authors vouch for the completeness and accuracy of the data and analyses. The views expressed herein are those of the authors and do not reflect the official policy or position of Merck & Co., Inc.