Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia: results from the ZYC101a protocol.
BACKGROUND
Little is known about the dynamics of human papillomavirus (HPV) during the follow-up of cervical intraepithelial neoplasia (CIN) 2/3 after biopsy.


METHODS
A 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.


RESULTS
Of 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.


CONCLUSIONS
The 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.
Crum
Christopher P
CP
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusettsm USA. cpcrum@rics.bwh.harvard.edu.
Beach
Kathleen J
KJ
Hedley
Mary L
ML
Yuan
Liping
L
Lee
Kenneth R
KR
Wright
Thomas C
TC
Urban
Robert G
RG
D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D017322:Clinical Trials, Phase II as Topic; D004247:DNA / Q000627:therapeutic use*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D009693:Nucleic Acid Hybridization; D027383:Papillomaviridae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy / Q000473:pathology / Q000821:virology*
D000998:Antiviral Agents; D004279:DNA, Viral; C482279:ZYC101a; D004247:DNA