• Christopher P Crum, Kathleen J Beach, Mary L Hedley, Liping Yuan, Kenneth R Lee, Thomas C Wright, and Robert G Urban.
• Department of Pathology, Brigham and Women's Hospital, Boston, Massachusettsm USA. cpcrum@rics.bwh.harvard.edu.
• J. Infect. Dis. 2004 Apr 15; 189 (8): 1348-54.

BackgroundLittle is known about the dynamics of human papillomavirus (HPV) during the follow-up of cervical intraepithelial neoplasia (CIN) 2/3 after biopsy.MethodsA total of 127 women with biopsy-confirmed CIN2/3 were enrolled in a phase 2 double-blinded, randomized, placebo-controlled clinical trial of ZYC101a. Colposcopic, cytologic, and HPV testing were performed over the course of 6 months, before a loop electrical surgical excision procedure was performed at study exit.ResultsOf the women tested, 99% were found to be HPV positive at study entry, 50% were found to be HPV type 16 positive at study entry, 22% were found to be positive for multiple HPV types at study entry, and 37% were found to be positive for additional HPV types during follow-up. Of those with a histologic outcome of CIN1 at study exit, 78% were found to be positive for additional HPV types; in 39%, the original type was replaced with a new HPV type. Virus load at study entry did not predict outcome, but pre-study-exit virus load correlated with a histologic outcome of any CIN, and changes in virus load correlated with risk for an outcome of CIN2/3 at study exit.ConclusionsThe type and number of HPVs at study entry, detection of additional viral types, and virus load changes during follow-up influence histologic outcome at study exit. An outcome of CIN1 at study exit is most likely due to additional HPV infections, rather than morphologic reversion of CIN2/3 to CIN1. Knowledge of the dynamics of HPV infection during the biopsy-to-excision period is critical to understanding the natural history of HPV infection, its contribution to disease outcome, and interpretations of drug efficacy.

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